Download Ongoing Clinical Trials Posters II

Ongoing Clinical Trials Posters II
Thursday, February 10, 2011, 6:15 pm - 6:45 pm
Presentation Number: CT P1
PI Coordinator Affiliation: University of California, San Francisco
PI Coordinator Name: S. Claiborne Johnston
Trial Abbreviation: The POINT Trial
Trial Contact Information: Mary Farrant, MBA BSN RN, University of California San Francisco Stroke
Sciences Group, San Francisco, California, United States, 94143, Phone 1-415-502-2096, E-mail
[email protected]
Trial Email: [email protected]
Trial Name: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
Trial Registry Number ID: NCT00991029
Trial Sponsor: University of California, San Francisco, National Institute of Neurological Disorders and Stroke
(NINDS)
Trial Web Site: http://pointtrial.org/
Publishing Title: The POINT Trial
Author Block: S. Claiborne Johnston, J Donald Easton, Univ of California San Francisco, San Francisco,
CA
Abstract Body:
Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT) Trial, is a prospective, randomized,
double-blind, multicenter trial with the primary null hypothesis that, in patients with TIA or minor ischemic stroke
treated with aspirin 50-325 mg/day, there is no difference in survival free of ischemic stroke, myocardial
infarction, and ischemic vascular death at 90 days in those treated with clopidogrel (600 mg loading dose then
75 mg/day) compared to placebo when therapy is initiated within 12 hours of onset. Subjects are over 18 years
of age with high-risk TIA (defined as an ABCD2 score > 4) or minor ischemic stroke (with NIHSS < 3) and each
subject is followed for 90 days from randomization. A total of 4,150 patients will be recruited and the trial will be
completed in 7 years. The first subject was enrolled on May 28, 2010.
Principal Investigator: S. Claiborne Johnston, MD, PhD, University of California, San Francisco
Co-Principal Investigator: J. Donald Easton, MD, University of California, San Francisco
Contact: Mary Farrant, MBA BSN RN, University of California San Francisco Stroke Sciences Group, San
Francisco, California, United States, 94143, Phone 1-415-502-2096, E-mail [email protected].
Number of Centers: 150
Sponsor: University of California, San Francisco, National Institute of Neurological Disorders and Stroke
(NINDS)
Collaborators: Neurological Emergencies Treatment Trials Network (NETT), Medical University of South
Carolina, The EMMES Corporation
Dates of Study: October 2009 - September 2016
ClinicalTrials.gov Identifier: NCT00991029
Characters: 1670; Words: 243
Author Disclosure Block: S. Johnston: None. J. Easton: None.
Presentation Number: CT P2
PI Coordinator Affiliation: Hospital Germans Trias i Pujol, Badalona (Spain)
PI Coordinator Name: Antoni Dávalos
Trial Abbreviation: ICTUS
Trial Contact Information: Julio J Secades, [email protected]
Trial Email: [email protected]
Trial Name: International Citicoline Trial on acUte Stroke
Trial Registry Number ID: NCT00331890
Trial Sponsor: Ferrer Group
Trial Web Site: www.ferrergrupo.com
Publishing Title: ICTUS Study: International Citicoline Trial on acUte Stroke (update 2011)
Author Block: Antoni Dávalos, Hosp Germans Trias i Pujol, Badalona, Spain; José Alvarez-Sabín, Hosp de
la Vall d'Hebron, Barcelona, Spain; José Castillo, Hosp Clínico Univrio de Santiago, Santiago de Compostela,
Spain; Erik Cobo, Univ Politècnica de Catalunya, Barcelona, Spain; Exuperio Díez-Tejedor, Hosp Univrio La
Paz, Madrid, Spain; Jose Ferro, Hosp de Santa Maria, Lisbon, Portugal; Eduardo Martínez-Vila, Clínica Univria
de Navarra, Pamplona, Spain; Julio J Secades, Ferrer Group, Barcelona, Spain; for the ICTUS Trial
Investigators
Abstract Body:
Background: Citicoline is a safe drug approved in some countries for the treatment of acute ischemic stroke.
The drug has shown some evidence of efficacy in a data pooled analysis, based on four clinical trials
performed in USA with oral citicoline given within 24 hours from symptoms onset.
Trial Steering Committee: Antoni Dávalos (Chairman), José Alvarez-Sabín, José Castillo, Erik Cobo
(Statistician), Exuperio Díez-Tejedor, Jose Ferro, Savion Gropper, Eduardo Martínez-Vila, Julio J Secades.
Data Safety Monitoring Board: Kennedy R Lees (Chairman), Steve Warach, John Whitehead (Statistician).
Purpose: To confirm the results obtained in the data pooled analysis.
Design: Multicenter, randomized (under minimization), double-blind, placebo-controlled trial, based on a
sequential analysis (triangular model).
Sample Size: The study will follow a sequential analysis, with the first approach to test the efficacy with 1000
patients, and the second one, with 1533 patients. The upper limit has been established in 2600 patients. This
design has 80% power to establish a treatment effect of 1.26 (common odds ratio).
Centers: 26 centers in Spain, 8 in Portugal and 10 in Germany
Study Population: Male or female, ≥ 18 years old, treated within 24 hours of symptoms onset, with a
measurable focal neurological deficit lasting for a minimum of 60 minutes. Baseline NIHSS score ≥ 8, with a
neuroimage compatible with the diagnosis of acute ischemic stroke and symptoms referable to MCA territory.
Pre-stroke mRS ≤ 1. Signed informed consent is mandatory.
Interventions: Patients will be randomized in a 1:1 ratio to receive either citicoline or placebo. Citicoline forms:
1000 mg ampoules (4 cc) and 500 mg tablets. Daily dosage: 1000 mg/12 h i.v. during the first three days and
orally from the fourth day until the end of the 6 weeks treatment period.
Outcome Endpoints: Primary end-point will consist in a global score test combining three measures of
success evaluated 12 weeks after treatment on the basis of intention-to-treat criteria: neurological (NIHSS) ≤
1), disability (MRS ≤ 1), and activities of daily life (BI ≥ 95), averaged using a Global Test. Secondary
endpoints: Results of the single scales at week 12. Formal training and certification in the use of mRS and
NIHSS are mandatory.
Safety Endpoints: Vital signs, adverse events, symptomatic hemorrhagic transformation in patients treated
with rTPA (ECASS criteria), neurological deterioration, mortality, and concomitant medication records
Statistical Analysis: The main analysis will consist of a Global Test combining the three measures of success
on the basis of intention-to-treat criteria applying LOCF. A patient who dies before 12 weeks will be considered
to have failed on all three measures.
Trial Status: All the centers are open. Close to 1900 patients are expected to be included by February 2010.
The second interim analysis on 1533 patients will be completed before the conference.
Registers:EudraCT Nº 2005-004825-25; ClinicalTrials.gov NCT00331890; Stroke Trials Registry
Author Disclosure Block: A. Dávalos: Research Grant; Modest; Ferrer Group. Speakers; Modest; Ferrer
Group. Honoraria; Modest; Ferrer Group. Consultant/Advisory Board; Modest; Ferrer Group. J. Alvarez-Sabín:
Research Grant; Modest; Ferrer Group. Consultant/Advisory Board; Modest; Ferrer Group. J. Castillo:
Research Grant; Modest; Ferrer Group. Honoraria; Modest; Ferrer Group. Consultant/Advisory Board; Modest;
Ferrer Group. E. Cobo: Other Research Support; Modest; Ferrer Group. Honoraria; Modest; Ferrer Group.
Consultant/Advisory Board; Modest; Ferrer Group. E. Díez-Tejedor: Research Grant; Modest; Ferrer Group.
Honoraria; Modest; Ferrer Group. Consultant/Advisory Board; Modest; Ferrer Group. J. Ferro: ; Ferrer Group.
E. Martínez-Vila: ; Ferrer Group. J.J. Secades: Employment; Significant; Ferrer Group.
Presentation Number: CT P3
PI Coordinator Affiliation: University of Pennsylvania; Haukeland University Hospital - Bergen, Norway; Duke
University; Rigshospitalet - Copenhagen, Denmark
PI Coordinator Name: Scott E. Kasner, Lars Thomassen, John F. Rhodes, Lars Søndergaard
Trial Abbreviation: REDUCE
Trial Contact Information: Erin McDowell W.L. Gore & Associates, Inc. Medical Products Division 4250 West
Kiltie Lane Flagstaff, AZ 86001 USA US Telephone: 928-864-4214 US Facsimile: 928-864-4952 EU
Telephone: 011-928-864-4214 EU Facsimile: 011-928-864-4952
Trial Email: [email protected]
Trial Name: GORE HELEX™ Septal Occluder and Antiplatelet Medical Management for Reduction of
Recurrent Stroke or Imaging-Confirmed TIA in Patients with Patent Foramen Ovale (PFO) - The Gore
REDUCE Study
Trial Registry Number ID: NCT00738894
Trial Sponsor: W.L. Gore & Associates, Inc.
Trial Web Site: http://clinicaltrials.gov/ct2/show/NCT00738894
Publishing Title: GORE HELEX Septal Occluder and Antiplatelet Medical Management for Reduction of
Recurrent Stroke or Imaging-Confirmed TIA in Patients with Patent Foramen Ovale (PFO) - The Gore
REDUCE Study
Author Block: Scott E Kasner, Univ of Pennsylvania, Philadelphia, PA; The Gore REDUCE Study
Investigators
Abstract Body:
Rationale: The relationships between cryptogenic stroke and patent foramen ovale (PFO) are complex, and
the role of percutaneous closure for prevention for recurrent stroke remains promising but uncertain.
Objective: The REDUCE Study is designed to demonstrate that PFO closure with the GORE HELEX Septal
Occluder plus antiplatelet medical management is safe and effective and reduces the risk of recurrent stroke or
imaging-confirmed transient ischemic attack (TIA) when compared to antiplatelet medical management alone
in patients with a PFO and history of cryptogenic stroke or imaging-confirmed TIA.
Design: Multicenter, multinational, randomized clinical trial.
Population:
• 664 men and Women, age 18 - 60 years
• Cryptogenic ischemic stroke or imaging-confirmed TIA
• Presence of Patent Foramen Ovale (PFO) confirmed by transesophageal echocardiography (TEE)
• No evidence of an alterative etiology for stroke
Intervention: Participants will be randomized 2:1 to PFO closure with the GORE HELEX Septal Occluder plus
antiplatelet medical management vs. antiplatelet medical management alone. Patients will be followed to 2
years for the primary endpoint, and up to 5 years for secondary endpoints.
Primary Outcome: Time to recurrent stroke or imaging-confirmed TIA, or death due to stroke through 24
months post-randomization. All events will be adjudicated by a blinded clinical events committee.
Secondary Outcomes: Proportion of participants with new ischemic lesions on MRI at 2 years compared to
MRI obtained at baseline; systemic embolic events; PFO closure in device-arm subjects by transthoracic
echocardiography (TTE); device- and procedure-related adverse events; time to recurrent stroke or imagingconfirmed TIA, or death due to stroke through 60 months post-randomization.
Statistical Analysis: Time to recurrent stroke or imaging-confirmed TIA will be compared using an unadjusted
log-rank test and presented using Kaplan-Meier methods. The primary analysis will be by intention-to-treat.
Trial Status: Enrollment is ongoing at a maximum of 50 investigational sites in the United States, Denmark,
Finland, Sweden, and Norway with no per-site subject limit.
Author Disclosure Block: S.E. Kasner: Research Grant; Significant; Gore PI grant to the Univ of Penn.
Presentation Number: CT P4
PI Coordinator Affiliation: U of Cinti, Mayo, Cleveland Clinic, Columbia, GCB&S, U of Maryland, U of Florida,
Notre Dame, NW U, Stanford, Brigham & Women's, USCF, U of Virginia, U of Washington, U of Alabama,
Mass Gen'l, U. of Michigan, Johns Hopkins, Wash. U. STL, Allegheny
PI Coordinator Name: J. Broderick MD; L. Sauerbeck, RN, MS
Trial Abbreviation: FIA II
Trial Contact Information: 800-503-3427
Trial Email: [email protected]
Trial Name: The Familial Intracranial Aneurysm Study II
Trial Registry Number ID: NCT00071565
Trial Sponsor: NIH Division of Neurological Disorders and Stroke
Trial Web Site: www.FIAStudy.org
Publishing Title: The Familial Intracranial Aneurysm Study II
Author Block: Laura Sauerbeck, Univ of Cincinnati, Cincinnati, OH; FIA Investigators
Abstract Body:
Background: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about
30,000 people per year in the United States. Unruptured IAs are estimated to be present in at least 1.0% of the
population. The goal of this National Institutes of Health funded, multi-center study is to identify genes that
increase the risk of developing saccular IAs. During the first phase of the FIA study we identified COL9A1
(collagen 9A1 gene) and PDE1A (phosphodiesterase 1A gene) as high priority candidate genes based not only
the strength of the association with FIA but also on their biological function. Phase II of the study will collect
families and sporadic cases of IA for replication of these findings, as well as genes identified by other studies.
Subjects: 200 families with multiple family members diagnosed with IA, along with 1800 sporadic cases of IA
will be enrolled as a replication data set through August 31, 2011.
Families that qualify include:
1. Two or > alive affected siblings.
2. At least 2 affected siblings, one of who is alive and the other whose genotype can be reconstructed.
3. > three affected family members, two of who are both alive and have living connecting relatives.
4. > three affected family members, one of whom alive, at least one who can be reconstructed and there are
living connecting relatives.
Exclusion Criteria for both family and sporadic cases:
1. Fusiform-shaped or IAs which are part of an arteriovenous malformation.
2. Family history of polycycstic kidney disease, Ehlers Danlos Syndrome, Marfan’s Syndrome, Fibromuscular
Dysplasia, or Moya-Moya.
3. Failure to obtain informed consent (IC).
Methods: After obtaining an IC each subject is administered questionnaires covering medical history,
environmental risk factors, and demographics. A blood specimen is also obtained from each subject. DNA
extraction and immortalization of cell lines occurs at the NINDS repository located at Coriell Institute for
Medical Research. Performance of GWAS of these subjects will take place when collection is completed. We
plan to compare these IA cases with age and gender-matched controls with available genotype data from
collaborating databases such as ARIC. The final step will be a comparison of genotypic and phenotypic data
from all approximately 2400 white IA familial and non-familial cases from FIA I & II with 5000+ age and gender
matched stroke/IA free controls form collaborating databases. SNPs and gene regions that are replicated in
white populations will be tested in our 600+ families as well as minority populations of IA cases from FIA I and
II and minority controls from FIA I/II and ARIC.
Results: During FIA I 441 families (2800 subjects) were completely characterized. To-date in FIA II ~ 1230
sporadic subjects and 54 families has been enrolled.
Study Centers: UC (Coordinating/Recruiting Ctr); (PI) J Broderick, Study Manager: L. Sauerbeck, CO-PI D
Woo (C) K. Franklin; Statisical Center: Indiana University: T Foroud: NINDS Repository (PI) M. D’Andrea; UC
Genotyping Center (PI) R. Deka: Recruiting Centers: Mayo Clinic (PI) R. Brown Jr (Cs) L Jaeger, D
Gravenhof; Cleveland Clinic (PI) P. Rassmussen (Cs) D Andrews-Hinders, L. Strozniak; Columbia Univ. (PI)
E.S. Connolly (C) L Lewis; Univ. of Florida (PI) S. Lewis (C) T. Sheehan; Goodman Campbell Brain& Spine.
(PI) T. Payner, (C) N Miracle; Univ. of Maryland (PI) F. Aldrich (Cs) C. Aldrich, K Booker; Notre Dame (PI) G
Rouleau (C) K. Boisvert; Northwestern Univ. (PI) H Batjer (C) S. Thompson; Stanford Unvi. (PI) G Steinberg
(Cs) M Coburn, S Dunn; Brigham & Women’s (PI) R Du(C) R Brach; UCSF (PI) N Ko, (C) P Buekea; Univ of
Virginia (PIs) K Lui, B Worrall (C) E. Rost Ruffner, S Raja; Univ of Washington (PI) D. Tirschell (C) P Tanzi;
Univ. of Alabama (PI) W. Fisher (C) K Lamb; Massachusetts General (PI) C. Ogilvy (C) M Whalen; Univ. of
Michigan (PI) A Pandey (C) K Maddox; Johns Hopkins (PI) D Gandhi (C) A Jones; Washington Univ. STL (PI)
C Derdeyn (C) L Shinawi; Allegheny Gen. (PI) K Aziz (C) L Fletcher
Author Disclosure Block: L. Sauerbeck: Research Grant; Significant; Salary Support.
Presentation Number: CT P5
PI Coordinator Affiliation: University of Cincinnati Academic Health Center
PI Coordinator Name: Joseph P. Broderick; Joyce Zeigler
Trial Abbreviation: IMS III
Trial Contact Information: Program Manager, Judith Spilker, [email protected], 513-558-4350.
Administrative Coordinator, Rose Beckmann, [email protected], 513-558-3907. http://www.ims3.org
Trial Email: [email protected]
Trial Name: The Interventional Management of Stroke (IMS) III Trial
Trial Registry Number ID: NCT00359424
Trial Sponsor: NINDS/University of Cincinnati
Trial Web Site: www.ims3.org
Publishing Title: The Interventional Management of Stroke (IMS) III Trial: An Ongoing Phase III Trial
Author Block: Thomas A. Tomsick, Joseph P. Broderick, Univ of Cincinnati, Cincinnati, OH; for the IMS III
Investigators
Abstract Body:
BACKGROUND AND PURPOSE: The IMS I and II pilot trials showed that the combined intravenous (IV) and
intra-arterial (IA) approach to recanalization may be more effective than standard IV rt-PA (Activase®) alone
for moderate-to-large (NIHSSS ≥10 or 8-9 with positive CTA) strokes, and with a similar safety profile.
Therefore, the primary objective of this NIH-funded, Phase III, randomized, multi-center, open-label clinical trial
is to determine whether a combined IV/IA approach to recanalization is superior to standard IV rt-PA alone
when initiated within three hours of acute ischemic stroke onset.
METHODS: A projected 900 subjects with moderate-to-large ischemic strokes between ages 18-82 will be
enrolled at 50+ centers in the United States, Canada, Australia and Europe. Both approaches must have IV
treatment initiated within three hours of stroke onset. Subjects will be randomized in a 2:1 ratio with more
subjects enrolled in the combined IV/IA group. The IV rt-PA alone group will receive the full standard dose (0.9
mg/kg, 90 mg max [10% as bolus]) of rt-PA intravenously over an hour. The combined IV/IA group will receive
a lower dose of rt-PA (~ 0.6 mg/kg, 60 mg max) over 40 minutes followed by immediate angiography. If a
treatable thrombus is not demonstrated, no IA therapy will be administered. If an appropriate thrombus is
identified, treatment will continue with either the Concentric Merci® Retriever, the Penumbra System™
thrombus-removal device, infusion of rt-PA and delivery of low-intensity ultrasound at the site of the occlusion
via the EKOS® Micro-Infusion Catheter (in US only), or infusion of rt-PA via a standard micro-catheter. New
devices will be evaluated as they become clinically available. The choice of IA strategy will be made by the
treating neurointerventionalist. IA treatment must begin within 5 hours and be completed within 7 hours of
stroke onset. The primary outcome measure is a favorable clinical outcome, defined as a modified Rankin
Score (mRS) of 0-2 at 3 months. The primary safety measure is mortality at 3 months and symptomatic ICH
within the first 36 hours after onset. Finally, a secondary objective of the IMS III Trial is to determine the costeffectiveness of the combined IV/IA approach as compared to standard IV rt-PA.
CONCLUSIONS: The IMS III Trial will develop and maintain a network of interventional centers to test the
safety, feasibility, and potential efficacy of a combined IV/IA approach to recanalization using intra-arterial
infusion of rt-PA and/or FDA-approved catheter devices. As of October 11, 2010, 434 subjects had been
randomized.
Author Disclosure Block: T.A. Tomsick: Research Grant; Significant; Neurointerventional PI NINDS funded
IMS III. J.P. Broderick: ; PI NINDS funded SPOTRIAS Center, includes CLEAR-ER, STOP-IT clinical trials, PI
NINDS funded IMS III, PI NINDS funded FIA, PI NINDS funded T-32 Cerebrovascular Fellowship Training
Program for Cerebrovascular Disease, Co-Investigator NINDS funded GERFHS, Co-Investigator NINDS
funded IRIS, Co-Investigator NINDS funded CREST, Co-Investigator NINDS funded COSS, Co-Investigator
NINDS funded SWISS. Other Research Support; Significant; Genentech supplies study drug to IMS III/CLEARER, EKOS Corp. supplies catheter devices for IMS III, Schering Plough supplies drug for CLEAR-ER.
Honoraria; Modest; Genentech, Inc., stroke advisory board, PhotoThera, stroke advisory board, Oakstone
Medical Publishing, speaker.
Presentation Number: CT P6
PI Coordinator Affiliation: Yale School of Medicine
PI Coordinator Name: Walter N. Kernan
Trial Abbreviation: IRIS
Trial Contact Information: [email protected]
Trial Email: [email protected]
Trial Name: Insulin Resistance Intervention after Stroke Trial
Trial Registry Number ID: NCT00091949
Trial Sponsor: National Institutes of Neurological Disorders and Stroke
Trial Web Site: www.iristrial.org
Publishing Title: The Insulin Resistance Intervention after Stroke (IRIS) Trial
Author Block: Walter Kernan, Yale Schoool of Med, New Haven, CT; Karen L Furie, Massachusetts General
Hosp, Boston, MA; Mark Gorman, Univ of Vermont, Burlington, VT; Peter Guarino, Yale Sch of Med, New
Haven, CT; Ralph I Horwitz, Stanford Univ, Palo Alto, CA; Silvio Inzucchi, Anne M Lovejoy, Catherine M
Viscoli, Lawrence H Young, Yale Schoool of Med, New Haven, CT
Abstract Body:
RATIONALE: Among persons who survive an ischemic stroke or TIA, a major source of morbidity and
mortality is recurrent stroke and myocardial infarction. Even with current therapies, within 5 years 18-25% of
patients will have a recurrent stroke and 10-12% will have a myocardial infarction. The IRIS trial will test the
effectiveness of pioglitazone as a new potential preventive therapy. Pioglitazone, a thiazolidinedione, increases
insulin sensitivity by activating the nuclear transcription factor PPARγ. In addition to decreasing insulin
resistance, pioglitazone improves dyslipidemia and endothelial function, reduces vascular inflammation,
promotes fibrinolysis, and slows carotid atherosclerosis. In clinical trials among diabetic patients, it reduced the
risk for stroke, MI, or death.
AIMS: To determine if pioglitazone, compared with placebo, is effective in lowering the risk for stroke or
myocardial infarction among men and women with a recent ischemic stroke or TIA. Secondary aims involve
prevention of diabetes and cognitive decline.
DESIGN: Randomized, double-blind, placebo-controlled clinical trial.
SAMPLE SIZE: 3136 participants will be recruited during 6 years and followed for an average of 4 years.
POPULATION:
- Non-diabetic men & women
- Ischemic stroke or TIA within 6 months of enrollment
- At least 40 years of age
- Able to give informed consent
- Insulin resistant (by HOMA-IR index from fasting insulin and glucose values).
INTERVENTION: Potential participants are tested for insulin resistance soon after the index stroke or TIA.
Those found to have insulin resistance are randomized to placebo or pioglitazone 15 mg tablets. The
medication dose is increased each month to a final dose of 3 tablets daily. Thereafter, participants will receive
tablets containing placebo or 45 mg pioglitazone for once daily use. After dose escalation, participants will be
followed with scheduled telephone calls and annual in-person visits. Blood is drawn annually for safety and
efficacy measures.
PRIMARY OUTCOMES: Stroke and myocardial infarction.
STATISTICAL ANALYSIS: Time to first event by intention to treat.
STATUS: Currently recruiting participants.
PROGRESS REPORT: 160 centers are actively recruiting participants. Among 5131 patients who have had
screening blood work, 3207 (63%) were insulin resistant; of these 3207, 144 (5%) had unrecognized diabetes.
A total of 2581 participants had been randomized as of October 1, 2010.
STEERING COMMITTEE: Arizona: B. Coull; California: R. Horwitz; Colorado: Greg Schwartz; Connecticut: W.
Kernan (PI, Chair), P. Guarino, S. Inzucchi, A. Lovejoy, P. Peduzzi, C. Viscoli, L. Young; Iowa: H. Adams;
Maryland: R. Conwit; Massachusetts: K. Furie; Ohio: D. Kleindorfer; Ontario: D. Spence; Oregon: W. Clark;
Vermont M. Gorman. Tel Aviv: D. Tanne. Australia: M. Parsons. UK: G. Ford. Germany: P. Ringleb. Italy: A.
Carolei.
SPONSOR: NINDS. Drug donated by Takeda Pharmaceuticals North America, Inc.
CONTACT: [email protected]
WEBSITE: iristrial.org
Author Disclosure Block: W. Kernan: Other Research Support; Significant; Takeda Pharmaceuticals North
America, Inc provides placebo tablets and active pioglitazone tablets to support the IRIS trial. In addition, the
company has provided a grant to support storage of blood. K.L. Furie: None. M. Gorman: None. P. Guarino:
None. R.I. Horwitz: None. S. Inzucchi: Consultant/Advisory Board; Modest; Intermittent consultation for
Takeda Pharmaceuticals North America. A.M. Lovejoy: None. C.M. Viscoli: None. L.H. Young: None.
Presentation Number: CT P7
PI Coordinator Affiliation: Newcastle University
PI Coordinator Name: Professor A D Mendelow
Trial Abbreviation: STICH II
Trial Contact Information: Dr Barbara A Gregson; [email protected]; Fax: +44 191 256 3268; Phone: +44 191
256 3139
Trial Email: [email protected]
Trial Name: Surgical Trial in Lobar Intracerebral Haemorrhage
Trial Registry Number ID: ISRCTN22153967
Trial Sponsor: Newcastle upon Tyne Hospitals NHS Foundation Trust
Trial Web Site: www.research.ncl.ac.uk/stich
Publishing Title: Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II)
Author Block: Barbara A Gregson, Newcastle Univ, Newcastle Upon Tyne, United Kingdom; STICH II
Investigators
Abstract Body:
Background
Spontaneous superficial intracerebral haemorrhage (ICH) accounts for 20% of all stroke-related sudden
neurological deficits and has the highest morbidity and mortality of all strokes. The role of surgery remains
controversial following the report of the international STICH trial which was neutral. Further analyses and metaanalysis have suggested that patients with lobar haemorrhage may benefit from early surgery.
Objective
STICH II aims to establish whether a policy of earlier surgical evacuation of haematomas in selected patients
with spontaneous lobar ICH will improve outcome compared to a policy of initial conservative treatment.
Design
STICH II is an international multicentre randomised parallel group trial.
Population
Patients for whom the treating neurosurgeon is in equipoise about the benefits and risks of early craniotomy
are eligible for the trial. Inclusion criteria include superficial, spontaneous lobar ICH on CT scan, best motor
score on the Glasgow Coma Score (GCS) of 5 or 6 and best eye score on the GCS of 2 or more, and volume
of haematoma between 10 and 100m. Patients are ineligible if the haemorrhage is due to an aneurysm or
angiographically proven arteriovenous malformation, is secondary to tumour or trauma or extends into the
basal ganglia, thalamic, cerebellar or brain stem. Patients are also ineligible if there is any Intraventricular
haemorrhage or hydrocephalus or if there is severe, pre-existing physical or mental disability or severe comorbidity which might interfere with assessment of outcome.
Six hundred patients will be recruited to the trial.
Intervention
The trial intervention is early evacuation of the haematoma, by craniotomy, within 12 hours of randomisation
combined with appropriate best medical treatment versus best medical treatment, combined with delayed
evacuation only if it becomes necessary later.
Outcome measures
Outcome is measured at six months via a structured postal questionnaire including the Glasgow Outcome
scale, Modified Rankin Scale and EuroQol.
Analysis
Analysis will be on an “intention to treat” basis. The primary analysis will be a simple categorical frequency
comparison using the chi-squared test for prognosis based favourable and unfavourable outcome at six
months.
Trial status
The STICH II trial is funded by the UK MRC and NIHR EME and sponsored by Newcastle upon Tyne Hospitals
NHS Trust. (ISRCTN22153967) Centre and patient recruitment are ongoing. At 15 October 101 centres from
32 countries had been recruited and 360 patients recruited from those 61 of those centres. Current details at
31 January 2011 of recruiting centres and recruited patients will be presented.
Author Disclosure Block: B.A. Gregson: Research Grant; Significant; Medical Research Council, NIHR
HTA, NIHR EME.
Presentation Number: CT P8
PI Coordinator Affiliation: University of Michigan
PI Coordinator Name: Lewis B. Morgenstern
Trial Abbreviation: NA
Trial Contact Information: Lewis B. Morgenstern, [email protected]
Trial Email: [email protected]
Trial Name: Outcomes of Intracerebral Hemorrhage without Early Do-Not-Resuscitate orders
Trial Registry Number ID: NA
Trial Sponsor: none
Trial Web Site: NA
Publishing Title: Outcomes of Intracerebral Hemorrhage without Early Do-Not-Resuscitate Orders: A
Multicenter Observational Registry
Author Block: Darin B Zahuranec, Univ of Michigan, Ann Arbor, MI; J Claude Hemphill III, Univ of California
San Francisco, San Francisco, CA; Kyra J Becker, Univ of Washington, Seattle, WA; Madeleine C Geraghty,
Providence Sacred Heart Medical Ctr, Spokane, WA; Brisa N Sanchez, Lewis B Morgenstern, Univ of
Michigan, Ann Arbor, MI
Abstract Body:
Rationale: Traditional outcome prediction models suggest that patients with severe intracerebral hemorrhage
(ICH) have a high risk of death. However, early do-not-resuscitate (DNR) orders and withdrawal or limitation of
life sustaining treatment (LST) are common after ICH. Predictions from prognostic models and clinical
experience assessing outcome are therefore confounded by the intensity of treatment provided. More data are
needed on the survival and functional outcome of ICH cases treated with full modern neurocritical care and
without early limitations of LST.
Study Goal: To compare the 30-day mortality and 90-day functional outcome of patients with severe ICH and
without early DNR orders to the predicted outcome based on a published ICH prognostic model.
Eligibility and Design: This is an observational study ongoing at 4 centers (University of Michigan, San
Francisco General Hospital, University of Washington, and Providence Sacred Heart Medical Center) where
the standard care pattern is to avoid early DNR orders or limitations of LST for ICH. Eligibility criteria include:
1) Age ≥ 18 years; 2) Spontaneous ICH; 3) Initial GCS of ≤ 12; and 4) No plans for DNR orders or withdrawal
of LST in the first 5 days of hospitalization. Patients with pre-existing DNR orders or clear prior wishes to
refuse aggressive treatment for severe illness are excluded.
The patient’s legally authorized representative is approached to consent for observational data collection only if
they have already agreed to a plan of full supportive treatment as part of regular clinical care. No specific
treatments are mandated by the study, and the patient or family may request a DNR order or withdrawal of
LST at any time. Data on ICH characteristics and inpatient treatment patterns are collected. Patients are
contacted at 30 and 90 days to determine vital status and functional outcome (modified Rankin Scale).
The predicted probability of death at 30 days for each patient will be calculated based on the ICH Score, and
the average predicted mortality for the cohort will be compared to the observed mortality. The planned sample
size of 105 cases study will provide 80% power to detect a 15% absolute difference between observed and
predicted mortality. An interim analysis is planned at 61 cases to screen for early evidence of a large effect
(absolute mortality difference of 20%). For the analysis of functional outcome, the observed proportion of cases
with severe disability (modified Rankin Scale of 5) will be compared to the proportion predicted from prior ICH
outcome studies. Pre-defined criteria for a positive study are a 15% absolute reduction in predicted mortality
with a less than 10% increase in the proportion of cases with severe disability.
Enrollment Progress: As of October 2010, 33 patients have been enrolled at the 4 centers. Any centers wishing
to participate should contact Dr. Morgenstern at [email protected].
Future Directions: This study will provide information on the outcome of severe ICH patients treated without
early DNR orders or withdrawal of LST. If there is a reduction in mortality without an increase in severe
disability, future educational intervention studies designed to reduce use of early treatment limitations after ICH
should follow.
Author Disclosure Block: D.B. Zahuranec: None. J. Hemphill: None. K.J. Becker: None. M.C. Geraghty:
None. B.N. Sanchez: None. L.B. Morgenstern: None.
Presentation Number: CT P9
PI Coordinator Affiliation: Georgetown University/UCLA Stroke Center
PI Coordinator Name: Chelsea Kidwell, MD/Judy Guzy, RN
Trial Abbreviation: MR RESCUE
Trial Contact Information: Gina Ramirez, [email protected], 202-687-5396
Trial Email: [email protected]
Trial Name: Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy
Trial Registry Number ID: NCT00389467
Trial Sponsor: NIH-NINDS
Trial Web Site: No website
Publishing Title: Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy
Author Block: Chelsea S. Kidwell, Georgetown Univ, Washington, DC; Reza Jahan, Sidney Starkman, Jeffry
R. Alger, Judy Guzy, UCLA Stroke Ctr, Los Angeles, CA; Gina Ramirez, Georgetown Univ, Washington, DC;
Timothy Schaewe, Jeffrey L. Saver, UCLA Stroke Ctr, Los Angeles, CA; MR RESCUE Investigators
Abstract Body:
Background and Objective: The general aim of the MR RESCUE Trial is to investigate whether multimodal
imaging can identify patients who will benefit substantially from mechanical embolectomy with the Concentric
Clot Retriever device or the Penumbra System for the treatment of acute ischemic stroke up to 8 hours from
symptom onset.
Design: MR RESCUE is a randomized, controlled, blinded-outcome phase IIB clinical trial.
Population Studied: Acute ischemic stroke patients with large vessel ICA or MCA occlusion enrolled within 8
hours of symptom onset. 120 patients will be enrolled.
Intervention: Patients are randomized to embolectomy (employing the Concentric Retriever or Penumbra
System) or standard medical care, with randomization stratified by penumbral pattern.
Outcome Measures: The primary outcome measure is the day 90 modified Rankin Score. Additional clinical,
angiographic, and MRI/CT radiographic outcome measures will also be assessed.
Analysis: The primary hypothesis is that the presence of substantial ischemic penumbral tissue on multimodal
imaging identifies patients most likely to respond to mechanical embolectomy for acute ischemic stroke. The
primary endpoint analyzed will be the distribution of scores on the modified Rankin Scale of global handicap at
90 days. Nested hypotheses test for 1) treatment efficacy in patients with penumbral regions pretreatment, and
2) absence of treatment benefit (equivalency) in patients without penumbral regions pretreatment.
Trial Status: Actively recruiting. 84 patients have been enrolled and 27 total sites are participating.
Author Disclosure Block: C.S. Kidwell: Research Grant; Significant; NINDS Grant Number P50 NS44378.
R. Jahan: ; NINDS Grant Number P50 NS44378. S. Starkman: ; NINDS Grant Number P50 NS44378. J.R.
Alger: ; NINDS Grant Number P50 NS44378. J. Guzy: ; NINDS Grant Number P50 NS44378. G. Ramirez: ;
NINDS Grant Number P50 NS44378. T. Schaewe: ; NINDS Grant Number P50 NS44378. J.L. Saver: ;
NINDS Grant Number P50 NS44378.
Presentation Number: CT P10
PI Coordinator Affiliation: Dept. of Neurology, Univ. of Heidelberg
PI Coordinator Name: Prof. Dr. Werner Hacke
Trial Abbreviation: SPACE2
Trial Contact Information: Dr. Peter Ringleb, [email protected]; fax +49 6221 56 8243
Trial Email: [email protected]
Trial Name: Stent-protected Angioplasty in Asymptomatic
Trial Registry Number ID: ISRCTN 78592017
Trial Sponsor: DFG/BMBF
Trial Web Site: www.space-2.de
Publishing Title: SPACE-2: Stent-protected Angioplasty in Asymptomatic Carotid Artery Stenosis vs.
Endarterectomy. A three-arm Clinical Trial
Author Block: Peter A Ringleb, Tilman Reiff, Hemasse Amiri, Univ hospital Heidelberg, Heidelberg,
Germany; SPACE 2 Collaborators
Abstract Body:
Current recommendations for treatment of asymptomatic carotid stenosis are essentially still based on data
from clinical trials performed at the end of the last century. There is increasing evidence of an improved of upto-date best-medical treatment to prevent cerebro- and cardiovascular risk as compared to a decade ago.
Considering a low risk rate with up-to-date pharmacotherapy, interventional therapies such as CEA and, in
particular, CAS need their specific justification because they are associated with considerable
periinterventional risks. SPACE-2 is a three-armed study with a randomized, controlled, open, multi-centre
design comparing best medical treatment with CEA and CAS. A hierarchical study protocol has been
developed with a superiority design of interventional vs. conservative treatment. In case superiority for CAS
and CEA is established vs best medical treatment alone, a non-inferiority comparison between the two
interventions will be performed. All patients are treated in accordance with their individual risk factor profile and
risk factors.. Primary safety endpoint is assessed as the rate of any stroke and death from any cause within 30
days of treatment. The primary efficacy endpoint is the cumulative rate of any stroke or death from any cause
within 30 days plus ipsilateral ischemic stroke within 5 years of follow up. Secondary endpoints also include
myocardial infarction. 3,640 subjects are envisaged to be enrolled in the clinical trial. Randomization has
started in Juli 2009. Currently, 34 centers in Germany, Austria and Switzerland are participating. The study is
funded by the German Research Foundation (DFG) and the Federal Ministry of Education and Research
(BMBF). The results of this trial are expected to be important for defining a proven standard for the best
possible treatment of asymptomatic carotid artery stenosis and would have wide impact on managing this
disease.
Author Disclosure Block: P.A. Ringleb: None. T. Reiff: None. H. Amiri: None.
Presentation Number: CT P11
PI Coordinator Affiliation: MUSC/Emory
PI Coordinator Name: Chimowitz/Lane
Trial Abbreviation: SAMMPRIS
Trial Contact Information: Bethany Lane, [email protected], 866-767-4594 (fax)
Trial Email: NA
Trial Name: Stenting versus Aggressive Medical Management for Preventing Recurrent stroke in Intracranial
Stenosis
Trial Registry Number ID: NCT00576693
Trial Sponsor: NIH/NINDS
Trial Web Site: http://www.sammpris.org/
Publishing Title: Stenting and Aggressive Medical Management for Preventing Recurrent stroke in
Intracranial Stenosis (SAMMPRIS)
Author Block: Colin Derdeyn, Washington Univ Sch of Med, St. Louis, MO; Marc Chimowitz, Medical Univ of
South Carolina, Charleston, SC; David Fiorella, State Univ of New York, Stony Brook, Stony Brook, NY; Tanya
Turan, Medical Univ of South Carolina, Charleston, SC; Bethany Lane, Michael Lynn, Emory Univ Sch of Med,
Atlanta, GA; Scott Janis, Natl Inst of Neurological Disorders and Stroke, Bethesda, MD
Abstract Body:
Background: Atherosclerotic stenosis of the major intracranial arteries is an important cause of ischemic
stroke. In the USA, intracranial stenosis causes approximately 50,000 strokes per year. The recently
concluded Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial provided key information regarding
the risk of future stroke in this population. Patients with severe stenosis (70%-99%), recent TIA or stroke,
female gender, and baseline NIH stroke scale > 1 were at highest risk of stroke in the territory of the stenotic
artery. Patients with severe stenosis (70% - 99%) and TIA or stroke within 30 days prior to enrollment had a
22.9% rate of ischemic stroke in the territory of the symptomatic artery at one year ((5% CI 15.4% - 30.4%). In
addition, patients with poorly controlled blood pressure and elevated low denisty lipoprotein (LDL) during
follow-up had a significantly higher rate of stroke, myocardial infarction (MI), or vascular death, compared with
patients with good control of these risk factors.
Stenting has emerged as a promising treatment for intracranial stenosis that is increasingly being used in
clinical practice in the USA and other developed countries. The efficacy of this procedure remains to be
proven. Given the clear impact of poorly controled risk factors on outcome, proof of efficacy will require a
randomized clinical trial comparing stenting and aggresive medical therapy vs. aggressive medical therapy
alone in patients with symptomatic intracranial arterial stenosis.
Objective and Primary Endpoints: To determine whether intracranial stenting (using the Wingspan selfexpanding nitinol stent) and intensive medical therapy is superior to intensive medical therapy alone for
preventing the primary endpoint (any stroke or death within 30 days after enrollment, any stroke or death within
30 days of re-angioplasty of symptomatic restenosis of the qualifying lesion, or stroke in the territory of the
symptomatic intracranial artery beyond 30 days) during a mean follow-up of two years in high-risk patients with
symptomatic stenosis of a major intracranial artery (MCA, carotid, vertebral, basilar).
Design: SAMMPRIS is an investigator-initiated, Phase III, multi-center, randomized, blindly-adjudicated clinical
trial of angioplasty and stenting with aggressive medical management versus medical management alone. The
anticipated sample size is 764 subjects. The primary inclusion criteria include recent ischemic symptoms
(within 30 days of enrollment) and a 70 to 99% atherosclerotic stenosis of a major intracranial artery amenable
to angioplasty and stenting. The aggressive medical therapy regimen consists of aspirin 325 mg per day for
entire follow-up, clopidogrel 75mg per day for 90 days after enrollment and aggressive risk factor management
primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70mg/dl. . Risk factor
management will be performed by the study neurologist at each site who will be assisted by an innovative,
evidence-based, educational, lifestyle modification program (INTERxVENT). Trial Status: Sixty sites (the
maximum allowed under the FDA IDE for the Wingspan stent) have been selected. Site selection was a two
step process involving credentialing of the study interventionalists by the SAMMPRIS Interventional
Credentialing Committee and a separate evaluation of the clinical site, based on the experience and availability
of a neurologist and study coordinator from the site, and a favorable review of the site by the 3rd party monitor
performing the qualifying site visit. The study began actively enrolling subjects November 18th, 2008. As of
October 30th, 2010, 386 subjects have been randomized at 43 active sites.
Author Disclosure Block: C. Derdeyn: Consultant/Advisory Board; Significant; W.L. Gore and
Associates. M. Chimowitz: None. D. Fiorella: ; Microvention/Terumo; Codman. T. Turan: None. B. Lane:
None. M. Lynn: None. S. Janis: None.
Presentation Number: CT P12
PI Coordinator Affiliation: Washington University School of Medicine
PI Coordinator Name: Derdeyn/Hantler
Trial Abbreviation: NA
Trial Contact Information: Nancy Hantler, CCRC
Trial Email: [email protected]
Trial Name: The Role of Cerebral Hemodynamics in Moyamoya Disease
Trial Registry Number ID: NCT00629915
Trial Sponsor: NINDS
Trial Web Site: http://neuro.wustl.edu/patientcare/clinicalservices/moyamoyacenter.htm
Publishing Title: The Role of Cerebral Hemodynamics in Moyamoya Disease
Author Block: Colin Derdeyn, Washington Univ Sch of Med, St. Louis, MO; Patricia Davis, Univ of Iowa Sch
of Med, Iowa City, IA; Shyam Prabhakaran, Rush Univ Sch of Med, Chicago, IL; Venkatesh Aiyagari, Univ of
Illinois at Chicago, Chicago, IL; Christina Ivan, Indiana Univ Sch of Med, Indianapolis, IN; Allyson Zazulia, Tom
Videen, Nancy Hantler, John Lee, Robert Grubb Jr, Gregory Zipfel, Phil Miller, Washington Univ Sch of Med,
St. Louis, MO
Abstract Body:
Background: Moyamoya phenomenon is secondary response to an obliterative vasculopathy involving the
large arteries at the base of the brain (Figure 1). The nature of this vasculopathy is unknown and may be
multifactorial. In the United States, moyamoya phenomenon most commonly affects women in their third and
fourth decades of life, and is frequently associated with ischemic stroke (1,2). The natural history of this
disorder is not known, nor is the benefit of surgical revascularization procedures. The mechanism of stroke in
these patients is not known, but hemodynamic factors are likely to play a major role. Severe hemodynamic
impairment has been shown to predict the risk of future stroke in patients with atherosclerotic carotid artery
occlusion (Figure 2) (3).
Objectives: The primary objective (Aim 1) is to test the hypothesis that increased oxygen extraction in the
cerebral hemisphere beyond the occlusive lesion is a predictor of subsequent risk of ipsilateral stroke.
Secondary aims are
(2A) to determine other predictive factors for stroke in this population;
(2B) to obtain preliminary estimates of the effects of different medical treatment regimens in this population;
(2C) to determine the temporal changes in hemodynamic impairment in medically treated patients;
(2D) to obtain determine the effects of surgery on hemodynamic impairment in the subset of patients that
undergo surgical revascularization;
(2E) to obtain estimates of surgical complication rates for patients with and without hemodynamic impairment.
Study Design: This is a prospective, blinded (to hemodynamic status), independently-adjudicated natural
history study 4. Some patients may undergo surgical revascularization procedures, based on the discretion of
treating physicians. The outcome of these patients will also be determined. On enrollment, all patients will
undergo regional measurements of cerebral oxygen extraction fraction (OEF) with positron emission
tomography (PET, Figure 2). Information on baseline clinical, laboratory, epidemiologic, and angiographic risk
factors will be obtained at the time of the PET study. Patients will be followed at six-month intervals to
determine the subsequent risk of ipsilateral stroke. All patients will return at one and three years for repeat PET
studies. We anticipate 50 patients will be enrolled over the next five years (10 per year). Each involved
hemisphere will be treated separately, for a total of 100 cerebral hemispheres at risk. Treating physicians and
patients will be blinded to the results of the PET scan. The primary objective (Aim 1) is to test the hypothesis
that increased oxygen extraction in the cerebral hemisphere beyond the occlusive lesion is a predictor of
subsequent risk of ipsilateral stroke.
Inclusion/Exclusion Criteria: Inclusion criteria:
. Adult > 18 years of age
. Capable of informed consent
. Clinical: Both asymptomatic and symptomatic patients will be included.
. Anatomic: Unilateral or bilateral imaging findings consistent with moyamoya collaterals (Suzuki stages 3 and
4) on digital subtraction, computed tomographic, or magnetic resonance angiography (after Suzuki and
Kodama, 1983, 5)
Exclusion criteria:
. Any other disease that might be responsible for the vasculopathy, including atherosclerosis,
neurofibromatosis, meningitis, sickle cell disease, skull base radiation therapy.
. Pregnancy: All women of child-bearing potential will be tested for pregnancy using a urine b-HCG test on the
day of the enrollment and follow up PET scans.
Data Analysis: Medically-treated hemispheres will be followed over the 5 - year study for the occurrence of
ipsilateral ischemic stroke, the primary endpoint. End point assessment will be made blind to PET data. The
threshold for abnormal OEF will be set prospectively as > 0.44. The primary statistical analysis will be a
comparison on the survival distribution of the time to stroke occurrence in hemispheres with increased OEF
versus those with normal OEF on initial PET studies. This analysis will be done using a log-rank test (Aim 1).
Cox’s proportional hazards models will be used to perform the comparison after adjusting the effect of other
covariates (Aim 2A). Depending on the variability of medical treatment, the treatment regimen may be added
as a variable (Aim 2B). Repeat PET measurements of OEF in medically and surgically treated hemispheres
will be compared to baseline measurements to determine if OEF improves over time in either group (Aims 2C
and 2D).
Trial Status: Trial is ongoing. Funding was received from the NIH in September 2006 (RO1 NS051631).
Enrollment is proceeding at target pace, with 46 subjects enrolled to date.
Participating Sites: Washington University, St Louis; University of Illinois-Chicago, Rush University, Indiana
University, University of Iowa
Author Disclosure Block: C. Derdeyn: None. P. Davis: None. S. Prabhakaran: None. V. Aiyagari:
None. C. Ivan: None. A. Zazulia: None. T. Videen: None. N. Hantler: None. J. Lee: None. R. Grubb:
None. G. Zipfel: None. P. Miller: None.
Presentation Number: CT P13
PI Coordinator Affiliation: The George Institute for Global health, Royal Prince Alfred Hospital, University of
Sydney
PI Coordinator Name: ANDERSON CRAIG
Trial Abbreviation: INTERACT2
Trial Contact Information: Craig Anderson [email protected]
Trial Email: [email protected]
Trial Name: The second Intensive Blood Pressure Reduction in Intracerebral Hemorrhage Trial
Trial Registry Number ID: ACTRN1260800036239, NCT00716079, ISRCTN73916115
Trial Sponsor: NHMRC
Trial Web Site: https://studies.thegeorgeinstitute.org.au/interact2
Publishing Title: Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2):
progress update on the largest clinical trial in ICH
Author Block: Craig Anderson, The George Inst for Global Health, Royal Prince Alfred Hosp, Sydney Univ,
Sydney, Australia; Yining Huang, Peking Univ First Hosp, Beijing, China; Jiguang Wang, Ctr for
Epidemiological Studies and Clinical Trials, Rui Jin Hosp, Shanghai, China; Emma Heeley, Candice Delcourt,
Richard Lindley, The George Inst for Global Health, Royal Prince Alfred Hosp, Sydney Univ, Sydney, Australia;
Christian Stapf, Lariboisiere Hosp, Paris, France; Christophe Tzourio, INSERM Unit 708, Paris, France;
Hisatomi Arima, The George Inst for Global Health, Royal Prince Alfred Hosp, Sydney Univ, Sydney, Australia;
Mark Parsons, John Hunter Hosp and Hunter Medical Res Unit, Newcastle, Australia; Bruce Neal, John
Chalmers, The George Inst for Global Health, Royal Prince Alfred Hosp, Sydney Univ, Sydney, Australia; The
INTERACT2 Investigators
Abstract Body:
Background: INTERACT2, an open, randomised, multicentre study, aims to establish the effectiveness of
early intensive blood pressure (BP) lowering treatment in acute ICH, the most serious and least treatable form
of stroke.
Methods A total of 2800 patients with ICH and elevated systolic BP (150-220 mmHg) and capacity to receive
intensive BP lowering treatment <6 hours of onset are to be included from ~140 sites worldwide. Simple
electronic data collection procedures are used and patients are centrally randomly assigned to intensive (target
systolic <140 mmHg) or conservative (target systolic <180 mmHg) BP management using routine intravenous
agents. Vital status and disability is assessed at 28 and 90 days. CT digital images are analysed centrally. The
trial is registered (ACTRN1260800036239, NCT00716079, ISRCTN73916115).
Results Since launch of the study in October 2008, 1400 patients have been randomised from China (46
sites), Australia (8), Europe (3 Austria, 1 Belgium, 11 France, 6 Germany, 3 Italy, 1 Portugal, 3 Spain). India
(5), Pakistan (1), and Chile (1). Preliminary data indicates similar patient and clinical characteristics to
INTERACT1, and good BP separation between groups. The clinical network has expanded to include sites
additional non-Asian sites.
Conclusions: Recruitment and quality parameters indicate INTERACT2 is on schedule to achieve the study
goals.
Author Disclosure Block: C. Anderson: None. Y. Huang: None. J. Wang: None. E. Heeley: None. C.
Delcourt: None. R. Lindley: None. C. Stapf: None. C. Tzourio: None. H. Arima: None. M. Parsons:
None. B. Neal: None. J. Chalmers: None.
Presentation Number: CT P14
PI Coordinator Affiliation: University of Minneosta
PI Coordinator Name: Adnan I. Qureshi
Trial Abbreviation: ATACH-II
Trial Contact Information: Bo Connelly, [email protected], (612) 625-6974
Trial Email: [email protected]
Trial Name: Antihypertensive Treatment of Acute Cerebral Hemorrhage II
Trial Registry Number ID: NCT01176565
Trial Sponsor: University of Minnesota - Clinical and Translational Science Institute
Trial Web Site: www.atach-2.com
Publishing Title: Antihypertensive Treatment of Acute Cerebral Hemorrhage II
Author Block: Adnan I. Qureshi, Univ of Minnesota, Minneapolis, MN; ATACH-II Investigators
Abstract Body:
The December 2003 report from a National Institute of Neurological Disorders and Stroke (NINDS)Workshop
on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of
blood pressure (BP) management in acute ICH as a leading priority. The Special Writing Group of the Stroke
Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure
evidence-based treatment of acute hypertension in ICH. To address important gaps in current knowledge, we
propose to conduct a five-year multi-center, randomized, controlled, Phase III trial with blinded outcome
ascertainment to determine the efficacy of early, intensive antihypertensive treatment using intravenous
nicardipine for acute hypertension in subjects with spontaneous supratentorial ICH.
The primary hypothesis of this large, streamlined, focused trial is that intensive systolic blood pressure (SBP)
reduction (SBP less than or equal to 140mmHg -- hereafter referred to as the intensive treatment) using
intravenous (IV)
nicardipine with treatment initiated within 3 hours of onset of ICH and continued for the next 24 hours reduces
the likelihood of death or disability at 3months after ICH (defined by modified Rankin scale [mRS] score of 46)by 10% or greater (absolute difference) compared with standard SBP reduction (SBP less than or equal to
180mmHg -- hereafter referred to as the standard treatment). The underlying mechanism for this expected
beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of
hematoma expansion observed in approximately 73% of patients with acute ICH.
The trial will recruit a maximum of 1,280 subjects with ICH who meet the eligibility criteria. The proposed
clinical trial is a natural extension of numerous case series, a subsequent pilot trial funded by NINDS, and a
preliminary randomized controlled trial in this patient population funded by the Australian National Health and
Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and
goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial.
The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP
reduction. The proposed trial will have important public health implications by providing necessary information
regarding the efficacy and safety of antihypertensive treatment of acute hypertension in subjects with ICH. BP
treatment represents a strategy that can be made widely available without the need of specialized equipment
and personnel and therefore can make a major impact upon outcome in patients with ICH.
Author Disclosure Block: A.I. Qureshi: Research Grant; Significant; National Institutes of Health, American
Heart Association. Other Research Support; Significant; Minnesota Medical Foundation, ESP Pharma, EKR
Therapeutics.
Presentation Number: CT P15
PI Coordinator Affiliation: Rush University Medical Center and University of Miami
PI Coordinator Name: Shyam Prabhakaran, MD, MS and Jose G. Romano, MD
Trial Abbreviation: MoSIS
Trial Contact Information: Iszet Campo-Bustillo, MPH, Phone: (305) 243-8018, Fax: (305) 243-7081, Email:
[email protected]
Trial Email: [email protected]
Trial Name: Mechanisms of Stroke in Intracranial Stenosis
Trial Registry Number ID: NCT01152944
Trial Sponsor: National Institute of Neurologic Disorders and Stroke
Trial Web Site: http://clinicaltrials.gov/ct2/show/NCT01152944
Publishing Title: Mechanisms of Stroke in Intracranial Stenosis (MoSIS - NCT01152944)
Author Block: Shyam Prabhakaran, Rush Univ Medical Ctr, Chicago, IL; David S Liebeskind, Univ of
California Los Angeles, Los Angeles, CA; Iszet Campo-Bustillo, Tatjana Rundek, Sebastian Koch, Univ of
Miami, Miller Sch of Med, Miami, FL; Miral D. Jhaveri, Rush Univ Medical Ctr, Chicago, IL; Michael Lynn,
Emory Univ, Atlanta, GA; Colin P. Derdeyn, Washington Univ Sch of Med, St. Louis, MO; Marc I. Chimowitz,
Medical Univ of South Carolina, Charleston, SC; Jose G. Romano, Univ of Miami, Miller Sch of Med, Miami, FL
Abstract Body:
Background: Intracranial atherosclerotic disease causes up to 10% of strokes in the United States and may
be the most important cause of ischemic stroke worldwide. The risk of recurrent stroke is as high as 25% over
2 years in those with stenosis 70-99%. The mechanisms for recurrent stroke remain unclear, however.
Progressive arterial narrowing, plaque instability (thrombo-embolism), and/or exhausted vasomotor reactivity
with impaired collateral flow are potential mechanisms that may elevate stroke risk.
Objective: Understand the mechanisms that underlie ischemic stroke in high-grade intracranial atherosclerotic
disease in order to determine predictors of recurrent stroke
Design: Prospective investigator-blinded ancillary study to the ongoing Stenting and Aggressive Medical
Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial
Study population: 100 medically-treated patients in SAMMPRIS trial with recently symptomatic (< 30 days)
high grade (70-99%) intracranial stenosis of the carotid, middle cerebral, vertebral, or basilar arteries. Besides
SAMMPRIS eligibility criteria and randomization to medical arm, MoSIS requires informed consent and
excludes patients with documented magnetic resonance imaging and/or transcranial Doppler (TCD)
contraindications.
Intervention: Baseline TCD with emboli detection and vasomotor reactivity, quantitative magnetic resonance
angiography (QMRA), post-processing perfusion angiography, and serial single-vessel TCD every four months
Outcome measure: Ischemic stroke in the territory of the stenotic artery
Analysis: The relationship between the time to ischemic stroke in the territory and each of the imaging
measurement variables (TCD, QMRA, and perfusion angiography) will be assessed using the log-rank test.
Using Cox-proportional hazards models, the hazard ratio for each imaging parameter will be calculated with
multivariable adjustments for relevant risk factors.
Status: Up to 15 sites in SAMMPRIS will participate in MoSIS
Principal Investigators: Shyam Prabhakaran, MD, MS and Jose Romano, MD
Affiliations: Rush University Medical Center and University of Miami
Coordinator: Iszet Campo-Bustillo, MPH, University of Miami
Sponsor: National Institute of Neurologic Disorders and Stroke
Contact: Iszet Campo-Bustillo, MPH, Clinical Research Building (C215), 1120 NW 14th St. Suite# 1361-1,
Miami, FL 33136, Phone: (305) 243-8018, Fax: (305) 243-7081, email: [email protected]
Website: http://clinicaltrials.gov/ct2/show/NCT01152944
Author Disclosure Block: S. Prabhakaran: None. D.S. Liebeskind: None. I. Campo-Bustillo: None. T.
Rundek: None. S. Koch: None. M.D. Jhaveri: None. M. Lynn: None. C.P. Derdeyn: None. M.I. Chimowitz:
None. J.G. Romano: None.
Presentation Number: CT P16
PI Coordinator Affiliation: Stanford University Stroke Center
PI Coordinator Name: Gregory W. Albers
Trial Abbreviation: DIAS-3 and DIAS-4
Trial Contact Information: H. Lundbeck A/S
Trial Email: [email protected]
Trial Name: Desmoteplase in Acute Ischemic Stroke
Trial Registry Number ID: NCT00790920 and NCR0085661
Trial Sponsor: H. Lundbeck A/S, Copenhagen, Denmark
Trial Web Site: www.lundbeck-dias.com
Publishing Title: Desmoteplase in Acute Ischemic Stroke: Status Update on the DIAS Clinical Trial Program
Author Block: Gregory W Albers, Stanford Univ Stroke Ctr, Palo Alto, CA; Rüdiger von Kummer, Univ of
Technology, Dresden, Germany; on behalf of the DIAS-3 and DIAS-4 Study Group
Abstract Body:
Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in Phase III of clinical development. The
structure of desmoteplase is similar to rt-PA (alteplase), but it does not contain the plasmin-sensitive cleavage
site and the lysine-binding Kringle 2 domain. As a result, desmoteplase, compared with rt-PA, has high fibrin
selectivity, an absence of neurotoxicity, and no apparent negative effect on the blood-brain barrier.
Evidence of safety and efficacy of desmoteplase was obtained in the Dose Escalation of Desmoteplase for
Acute Ischemic Stroke (DEDAS) and Desmoteplase in Acute Ischemic Stroke (DIAS) Phase II trials. The DIAS2 Phase III trial supported the safety profile of desmoteplase but did not replicate the positive efficacy findings
of DEDAS and DIAS. Post hoc analyses of patients with TIMI scores 0-1 revealed lower response rates in the
placebo group (18%) and higher response rates in the desmoteplase groups (36% and 27% for desmoteplase
90 µg/kg and 125 µg/kg, respectively). Therefore, in 2009, 2 large, randomized, double-blind, placebocontrolled, multinational Phase III trials were initiated (DIAS-3 and DIAS-4, n=800: NCT00790920 and
NCT00856661) to evaluate the efficacy and safety of a single intravenous bolus of 90 µg/kg desmoteplase
given 3-9 hours after onset of ischemic stroke (NIHSS score 4-24, age 18-85 y). Patients are selected with
occlusion or high-grade stenosis (TIMI 0-1) in proximal cerebral arteries as assessed by magnetic resonance
or computed tomography angiography. Whenever possible, additional perfusion-weighted imaging and
diffusion-weighted imaging assessments are done. Further trial information will be presented at this congress.
In support of the program, a DIAS trial network (hub-spoke model) has been implemented in the United States
that consists of both tertiary and community-based acute stroke centers managed by regional hub directors,
representing standard clinical practice for a majority of potential stroke patients. The initiative will provide an
opportunity to extend medical treatment to patients who would ordinarily not have access to thrombolytic
therapy.
In 2009, a Phase I desmoteplase trial was completed in healthy Japanese and Caucasian men, assessing the
safety, tolerability, and pharmacokinetics of desmoteplase at doses up to 90 µg/kg. The results of this study
were presented at the 2010 World Stroke Conference in Seoul. Subsequently, a randomized, double-blind,
placebo-controlled, dose-escalation Japanese Phase II trial was initiated in September 2010 (DIAS-J;
NCT01104467). The primary objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70
and 90 µg/kg 3-9 hours after onset of ischemic stroke in Japanese patients (n=48). Secondary objectives are
to evaluate clinical improvement up to day 90; recanalization and change in infarct size 18±6 hours after start
of treatment; and to study pharmacokinetics, pharmacodynamics and immunogenicity.
Desmoteplase is the only thrombolytic agent in late-stage development despite the high unmet treatment need
in acute ischemic stroke. Therefore, the results of the DIAS clinical trial program will be important for
physicians and patients in need of a safer, effective treatment for acute ischemic stroke.
Author Disclosure Block: G.W. Albers: Honoraria; Modest; H. Lundbeck A/S, Boerhinger Ingelheim. R. von
Kummer: ; H. Lundbeck A/S.
Presentation Number: CT P17
PI Coordinator Affiliation: David Geffen School of Medicine at UCLA
PI Coordinator Name: Jeffrey Saver, MD / Fiona Chatfield, RN
Trial Abbreviation: FAST-MAG
Trial Contact Information: Jeffrey Saver, MD / [email protected]
Trial Email: [email protected]
Trial Name: Field Administration of Stroke Therapy - Magnesium Phase 3 Clinical Trial
Trial Registry Number ID: NCT00059332
Trial Sponsor: NIH-NINDS
Trial Web Site: www.fastmag.info
Publishing Title: The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Phase 3 Clinical Trial
Author Block: Jeffrey L Saver, Geffen Sch of Med at UCLA, Los Angeles, CA; Marc Eckstein, Los Angeles
Fire Dept EMS and USC, Los Angeles, CA; Sam Stratton, OC EMS Agency and Harbor-UCLA Medical Ctr,
Los Angeles, CA; Frank Pratt, LA County Fire EMS, Los Angeles, CA; Scott Hamilton, Stanford, San
Francisco, CA; Robin Conwit, NIH-NINDS, Bethesda, MD; David S Liebeskind, Geffen Sch of Med at UCLA,
Los Angeles, CA; Gene Sung, Nerses Sanossian, Univ of Southern California, Los Angeles, CA; for the FASTMAG Investigators and Coordinators
Abstract Body:
BACKGROUND: Magnesium is neuroprotective in preclinical models of stroke and has been safe and shown
signals of potential efficacy when delivered early after onset of human cerebral ischemia. Delayed initiation of
neuroprotective agents has hindered past phase 3 neuroprotective agent trials.
OBJECTIVE: To demonstrate that paramedic initiation of intravenous magnesium sulfate within 2 hours
ofsymptom onset improves the longterm functional outcome of hyperacute stroke patients.
DESIGN: Multicenter, randomized, double-blind, placebo-controlled phase 3 trial.
POPULATION STUDIED: 1700 patients (850 in each arm) with acute stroke, including both cerebral infarction
and intracerebral hemorrhage patients. Inclusion criteria: 1) likely stroke as identified by the Los Angeles
Prehospital Stroke Screen (LAPSS), 2) age 40-95, 3) symptom onset within 2 hours of treatment initiation, 4)
deficit present ≥ 15 minutes.
INTERVENTION: Paramedics administer a loading dose of magnesium sulfate (Mg) or matched placebo in the
field, 4 grams over 15 minutes. In the ED, a maintenance infusion follows, 16 grams Mg or matched placebo
over 24 hours.
OUTCOME MEASURE(S): The primary endpoint is the modified Rankin Scale global measure of functional
outcome, assessed 90 days after treatment. Secondary endpoints include NIHSS (neurologic deficit), Barthel
Index (disability), and Stroke Impact Scale (quality of life).
ANALYSIS: The primary analysis will assess the difference in the distribution of mRS scores between treated
and placebo groups, employing the Cochran-Mantel-Haenszel test statistic (shift analysis).
TRIAL SITES: The trial is being conducted in two regional stroke systems: 1) Los Angeles County EMS,
including 31 EMS provider agencies, 41 stroke receiving hospitals, 228 ambulances, and 2200 paramedics;
and 2) Orange County EMS, including 13 EMS provider agencies, 9 stroke receiving hospitals, 125
ambulances, and 1250 paramedics. Site investigators include over 400 emergency physicians and over 150
neurologists, neurosurgeons, and hospitalists.
TRIAL STATUS: Through 11/1/2010, 1126 patients had been enrolled. Median interval from last known well to
start of study agent is 46 minutes. Treatment was initiated within 1 hour of onset in 73% and between 1-2
hours in 25%. Median pretreatment stroke severity on the Los Angeles Motor Scale (LAMS) is 4. Adjudicated
final diagnoses are acute cerebral ischemia in 73%, intracerebral hemorrhage in 24%, and stroke mimic in 3%.
Author Disclosure Block: J.L. Saver: None. M. Eckstein: None. S. Stratton: None. F. Pratt: None. S.
Hamilton: None. R. Conwit: None. D.S. Liebeskind: None. G. Sung: None. N. Sanossian: None.
Presentation Number: CT P18
PI Coordinator Affiliation: Mayo Clinic Florida/UMDNJ-New Jersey Medical School
PI Coordinator Name: Thomas G. Brott, MD/Alice J. Sheffet, Ph.D.
Trial Abbreviation: CREST
Trial Contact Information: Alice J Sheffet, [email protected], www.cresttrial.org, fax=973-972-8383,
phone=973-972-7718
Trial Email: [email protected]
Trial Name: Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): Long Term Follow-up
Trial Registry Number ID: NCT00004732
Trial Sponsor: NINDS/NIH
Trial Web Site: www.cresttrial.org
Publishing Title: Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): Long Term
Follow-up
Author Block: Alice J Sheffet, Susan E Hughes, MeeLee Tom, UMDNJ NJ MEDICAL SCHOOL, Newark, NJ;
Donald V Heck, Forsyth Radiological Associates, Winston-Salem, NC; Bart Demaerschalk, Mayo Clinic
Arizona, Scottsdale, AZ; Irfan Altafullah, Minneapolis Clinic of Neurology, Golden Valley, MN; David Chiu, The
Methodist Hosp, Houston, TX; Jenifer H Voeks, Jason Avery, Univ of Alabama at Birmingham, Birmingham,
AL; Mary E Longbottom, Thomas G Brott, for the CREST Investigators, Mayo Clinic Florida, Jacksonville, FL
Abstract Body:
BACKGROUND: Multisite clinical trials currently support guidelines for carotid treatment based on 2-4 years of
follow-up for patients living decades after revascularization. Designed to establish the relative efficacy of
carotid endarterectomy (CEA) versus carotid stenting (CAS), the NINDS-funded Carotid Revascularization
Endarterectomy versus Stenting Trial (CREST), completed enrollment July 18, 2008. Randomization of 2502
symptomatic (1321) and asymptomatic (1181) patients occurred at 117 North American sites. Primary results
were published July 1, 2010 for periprocedural and midterm outcomes with a median follow-up of 2.5 years.
The risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly
for CEA and CAS.
OBJECTIVE: Extension of CREST follow-up for up to ten years to evaluate the clinical and anatomic durability
of CAS versus CEA (as assessed by ipsilateral stroke and recurrent stenosis > 50%).
DESIGN: CREST (ClinicalTrials.gov NCT00004732) is an NINDS-funded, randomized, two-arm, multicenter
clinical trial with blinded endpoint adjudication. Extended follow-up of CREST CAS and CEA subjects includes
annual clinic visits and midpoint telephone visits (maximum 10 years follow-up; average 7.5 years).
POPULATION: Active post-procedure symptomatic and asymptomatic CREST subjects (n=2000) reconsented for up to 10 years of follow-up.
OUTCOMES: The primary aim is to assess CEA versus CAS in the prevention of ipsilateral stroke. Secondary
aims will 1) assess if there are effect modifiers of the long-term durability of the two procedures, such as age,
sex, pre-procedural degree of stenosis and symptomatic status, 2) assess if there is a temporal change or
pattern in the relative efficacy of the two procedures, 3) assess differences between groups in the rates of
restenosis or revascularization, 4) link Medicare-eligible CREST participants with inpatient and outpatient CMS
data files to assess patient outcomes and utilization of healthcare services.
ANALYSIS: Statistical analysis of the primary aim (time-to-event modeling with adjustment for major baseline
covariates) will assess post-procedural treatment differences from Day 31 up to ten years, providing 90%
power to detect a hazard ratio of 1.67.
TRIAL STATUS: On February 5, 2010, NINDS Council approved the extension of CREST long-term follow-up
through 2015. Protocol Amendment VI, approved by the DSMB, FDA, and UMDNJ IRB of Record (May 21 to
August 26, 2009) extends ongoing follow-up for up to 10 years. The visit schedule and forms have been
streamlined for efficient reporting of events and data collection necessary for the assessment of the longerterm differential effectiveness of CAS versus CEA. With the focus on long-term clinical outcomes, simplification
of the follow-up protocol will result in reduced patient/clinic burden and reduced cost. To date, 111 site IRBs
have approved long-term follow-up with 1064 CREST subjects re-consented for extended follow-up. Top reconsenting sites are: Central Baptist Hospital, Lexington, KY; CHA Hospital L’Enfant Jesus, Quebec City,
Canada; Oregon Health Science University, Portland, OR; University of Calgary, Calgary, Canada; and
Heritage Valley Health Systems, Beaver, PA. Continuing CREST follow-up will allow comparative assessment
of clinical and anatomical durability of CEA and CAS in symptomatic and asymptomatic patients for the longest
period in any carotid trial.
Author Disclosure Block: A.J. Sheffet: None. S.E. Hughes: None. M. Tom: None. D.V. Heck: Other
Research Support; Modest; Local Site PI on SAPPHIRE-WW, CHOICE, CABANA and ACT I trials. B.
Demaerschalk: None. I. Altafullah: ; Local Site PI of the CHOICE registry that is sponsored by Abbott. D.
Chiu: None. J.H. Voeks: None. J. Avery: None. M.E. Longbottom: None. T.G. Brott, for the CREST
Investigators: Honoraria; Modest; Sahs Memorial Lecture University of Iowa, VEITH Symposium, American
Academy of Neurology 62nd Annual Meeting, Heritage Valley Health System, American Society of
Neuroradiology 48th Annual Meeting, Massachusetts General Hospital, Pennsylvania Advances in Stroke.
Presentation Number: CT P19
PI Coordinator Affiliation: University of British Columbia/University of Texas Health Science Center at San
Antonio
PI Coordinator Name: Oscar Benavente/Robert Hart/Ana Roldan/Marie Benavente
Trial Abbreviation: SPS3
Trial Contact Information: Oscar Benavente, MD/[email protected]/604-822-1789
Trial Email: [email protected]
Trial Name: Secondary Prevention of Small Subcortical Strokes
Trial Registry Number ID: NCT00059306
Trial Sponsor: NIH/NINDS
Trial Web Site: www.sps3.org
Publishing Title: Secondary Prevention of Small Subcortical Strokes (SPS3)
Author Block: Ana Roldan, Marie Benavente, UNIVERSITY OF BRITISH COLUMBIA, VANCOUVER, BC,
Canada; Pablo Pergola, Gabriela Pergola, UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN
ANTONIO, SAN ANTONIO, TX; Leslie McClure, Jeff Szychowski, UNIVERSITY OF ALABAMA, Birmingham,
AL; Christopher Coffey, UNIVERSITY OF IOWA, Iowa, IA; Robin Conwit, NIH/NINDS, Bethesda, MD; Robert
Hart, UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO, San Antonio, TX; Oscar
Benavente, UNIVERSITY OF BRITISH COLUMBIA, VANCOUVER, BC, Canada
Abstract Body:
Background Small subcortical strokes(S3) account for about 25% of all brain infarcts, are very frequent
among Hispanic Americans(HA) and are usually due to cerebral small artery disease which predisposes to
vascular dementia. Over 2 million S3 survivors are at high risk of stroke recurrence and subsequently vascular
dementia; millions more suffer subclinical S3 and cognitive decline caused by the intrinsic disease of the small
penetrating cerebral arteries. No previous randomized trials have focused on secondary prevention after S3 or
subcortical TIA, optimal target levels of BP control after stroke and their relationship to cognitive decline, or
prevention of stroke and dementia in HA. Objectives Determine: if the combination of Aspirin 325
mg/d+Clopidogrel 75 mg/d is more efficacious than Aspirin 325 mg/d alone AND whether intensive BP
lowering (systolic <130 mmHg) is superior to usual hypertension management (systolic between 130-149
mmHg) in reducing stroke recurrence, cognitive decline and major vascular events in patients with
symptomatic S3 or subcortical Transit Ischemic Attack (TIA). Methods SPS3 is a randomized multicenter
clinical trial . Patients are assigned in a factorial design to 2 interventions: a. Aspirin 325 mg/d vs. Aspirin 325
mg/d+Clopidogrel 75 mg/d. (double-blinded). b. Two targets of systolic BP, “usual” (130-149 mmHg)
vs.“intensive” (<130 mmHg). (open-label with blinded event assessment). Will include 3000 participants with
symptomatic, MRI documented S3/subcortical TIA within the prior 6 months and without carotid stenosis or
major cardiac sources of embolism. Follow-up every 3 months for a mean of 3.5 yrs. Outcomes Recurrent
stroke (primary), cognitive decline, major vascular events and death. Trial Status 2865 patients from 8
countries are currently participating. The study will be completed on April 2012. Mean age is 63 yrs old; 63%
Male; 25% Hispanics.
Author Disclosure Block: A. Roldan: None. M. Benavente: None. P. Pergola: None. G. Pergola: None. L.
McClure: None. J. Szychowski: None. C. Coffey: None. R. Conwit: None. R. Hart: None. O. Benavente:
None.
Presentation Number: CT P20
PI Coordinator Affiliation: RESPECT Steering Committee
PI Coordinator Name: RESPECT Steering Committee
Trial Abbreviation: RESPECT Trial
Trial Contact Information: Kristine Veltum [email protected]
Trial Email: [email protected]
Trial Name: Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current
Standard of Care Treatment Trial
Trial Registry Number ID: NCT00465270
Trial Sponsor: AGA Medical Corporation
Trial Web Site: www.respectstudy.com
Publishing Title: Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current
Standard of Care Treatment (RESPECT) Trial.
Author Block: David Thaler, Tufts Medical Ctr, Boston, MA; John Carroll, Univ of Colorado, Denver, CO;
Jeffrey Saver, UCLA, Los Angeles, CA; Richard Smalling, Univ of Texas, Houston, Houston, TX; Brian van
Dorn, AGA Medical Corp, Plymouth, MN
Abstract Body:
PURPOSE: To investigate whether percutaneous PFO closure is superior to current standard of care medical
treatment in the prevention of recurrent embolic stroke. DESIGN: Multicenter, randomized, active control,
blinded adjudicated outcome, clinical trial. SAMPLE SIZE: 900 patients (450 per study arm). POPULATION
STUDIED: Patients age 18-60 with patent foramen ovale who have had a cryptogenic stroke due to presumed
paradoxical embolism within the last 270 days. INTERVENTIONS: Patients are randomly assigned to medical
therapy or PFO closure with the AMPLATZER PFO Occluder. Medical therapy options include aspirin alone,
coumadin alone, clopidogrel alone, or aspirin combined with extended-release dipyridamole. OUTCOME
MEASURES: The primary endpoint is recurrent nonfatal stroke, all-cause post-randomization death within 45
days of randomization or 30 days after implant whichever occurs last, or fatal ischemic stroke. The secondary
efficacy endpoints are complete closure of the defect at the six-month follow-up, time to recurrent symptomatic
cryptogenic nonfatal stroke or cardiovascular death, and TIA. STATISTICAL ANALYSIS: The superiority of the
device will be tested by using an exact binomial test of the proportion of device primary endpoint events to
primary endpoint events across both arms of the study, conditioned on the total number of events. CURRENT
STATUS AND BASELINE DEMOGRAPHICS: 807 patients have been enrolled as of October 31, 2010. The
graph below depicts progressive enrollment. Index strokes were located in the cerebral cortex (43%), deep
white matter [centrum semiovale and internal capsule] (3%), deep grey matter [basal ganglia and thalamus]
(10%), brain stem/cerebellum (13%) and in multiple territories (19%). Large infarcts (>3cm) occurred in 22% of
the patients. Most subjects (85%) showed PFO-shunting at rest, i.e. without Valsalva. Atrial septal aneurysms
(≥10mm) are present in 35%. Updated data will be presented.
Author Disclosure Block: D. Thaler: Consultant/Advisory Board; Modest; Consulting for AGA Medical.
Consultant/Advisory Board; Significant; minimal. J. Carroll: Consultant/Advisory Board; Modest; Consulting for
AGA Medical. Consultant/Advisory Board; Significant; minimal. J. Saver: Consultant/Advisory Board; Modest;
Consulting for AGA Medical. Consultant/Advisory Board; Significant; minimal. R. Smalling:
Consultant/Advisory Board; Modest; Consulting for AGA Medical. Consultant/Advisory Board; Significant;
minimal. B. van Dorn: Employment; Modest; Employee of AGA Medical - Statistician. Employment;
Significant; Employee.
Presentation Number: CT P21
PI Coordinator Affiliation: University of Cincinnati
PI Coordinator Name: Matthew Flaherty, MD / Traci Doellman, RN
Trial Abbreviation: STOP-IT Study
Trial Contact Information: Project Manager: Janice Carrozzella, RN, BA, CCRA; [email protected]; 513-4758797 / 513-475-8793
Trial Email: [email protected]
Trial Name: The Spot Sign for Predicting & Treating ICH Growth Study
Trial Registry Number ID: NCT00810888
Trial Sponsor: NIH / NINDS
Trial Web Site: www.STOPITSTUDY.org
Publishing Title: The Spot Sign for Predicting and Treating ICH Growth (STOP-IT) Study
Author Block: Matthew Flaherty, Univ of Cincinnati, Cincinnati, OH; The STOP-IT Study Investigators
Abstract Body:
Background:
Intracerebral hemorrhage (ICH) is estimated to affect 67,000 persons in the United States and 5,000 persons
in Canada annually and is associated with a 40-50% case-fatality rate. There are no proven treatments for
ICH. The demonstration that hematoma growth after ictus is common and associated with neurological decline
has spurred research into early hemostatic therapy to potentially improve patient outcomes.
Recombinant activated factor VII (rFVIIa) was proven to significantly reduce hematoma growth when
administered within four hours of symptom onset in two placebo-controlled, blinded, randomized clinical trials.
Because rFVIIa works to stop bleeding but should not otherwise affect the natural history of ICH, only patients
destined to have hematoma growth will benefit from this therapy. Ideally, clinicians will be able to identify
patients who will have significant hematoma growth regardless of their time of presentation and administer
hemostatic therapy to this group.
CT angiography (CTA) is a widely available, fast, non-invasive tool that has shown promise for predicting
hematoma growth. In multiple, recent retrospective case series patients with contrast extravasation within their
hematomas (the spot sign) had greater risk of subsequent hematoma growth and worse outcomes than
patients without extravasation.
The next step in this treatment paradigm is to confirm the ability of CTA to predict hematoma growth and to
explore the role CTA may play in the administration of hemostatic therapy.
Objectives:
• Determine the sensitivity and specificity of the CTA spot sign for hematoma growth.
o Working hypothesis: For patients scanned within five hours of stroke onset, the spot sign will have a high
sensitivity and specificity for hematoma growth.
• Determine the feasibility of using CTA to identify ICH patients at high risk of hematoma growth and to select
patients for randomization to treatment with rFVIIa or placebo.
o Working Hypothesis #1: Site investigators will determine the presence or absence of a spot sign in the acute
setting with a high degree of accuracy as compared to blinded over-read by a study neuroradiologist.
o Working Hypothesis #2: Use of CTA to identify candidates for randomization to rFVIIa versus placebo can be
done in a time-efficient manner
• Randomize ICH patients who present within five hours of symptom onset and have a spot sign to treatment
with rFVIIa versus placebo, in order to (a) determine if rFVIIa is effective at reducing hematoma growth among
patients with a spot sign and (b) provide preliminary efficacy data for this treatment paradigm.
o Working Hypothesis: Spot-positive patients treated with rFVIIa will have less hematoma growth than spotpositive patients treated with placebo.
Design:
STOP-IT will enroll patients with acute ICH less than five hours from symptom onset. Patients will be included
in one of two study arms. The first arm will be a multicenter, randomized, double-blind, placebo-controlled trial
comparing rFVIIa to placebo for treatment of patients with acute ICH and a spot sign on CTA. The second arm
will be a multicenter, prospective observational study of hematoma growth among patients without a spot sign
on CTA. Comparisons will be made between 1) patients with a spot sign randomized to placebo and patients
without a spot sign, in order to determine the value of the spot sign for predicting hematoma growth and 2)
patients who have a spot sign and are randomized to rFVIIa or placebo in order to determine the effect of study
drug upon hematoma growth.
Population:
Approximately 184 subjects with intracerebral hemorrhage fulfilling inclusion and failing no exclusion criteria
will be enrolled into one of two study arms at twelve clinical sites across the United States and Canada.
Interventions:
Eligible, consented subjects presenting within five hours of ICH onset will be qualified for enrollment into one of
two study arms in this multicenter phase II study. Patients who have a spot sign present on CTA will be
randomized 1:1 to treatment with either rFVIIa (80 mcg/kg - maximum dose volume 10.0 mL, equivalent to
maximum weight of 125 kg) or placebo. Patients without a spot sign will be enrolled in a prospective
observational arm and their data will be compared to spot-positive patients treated with placebo to determine
the sensitivity and specificity of the CTA spot sign for hematoma growth.
Outcome Measures:
Primary Outcome: Clinical
• Safety: Life-threatening thromboembolic complications defined as development of (1) acute myocardial
ischemia; (2) acute cerebral ischemia; and (3) acute pulmonary embolism through day 4 following completion
of study drug administration.
• The rate of hematoma growth among spot sign positive subjects at 24 hours, comparing subjects treated with
rFVIIa to those treated with placebo. Hematoma growth will be defined as a > 33% or > 6 cc increase in
volume.
Secondary Outcome: Clinical
• Incidence of other potentially study drug related thromboembolic complications such as deep venous
thrombosis and elevations in troponin not associated with ECG evidence of acute coronary syndrome through
day 90 following completion of study drug administration.
• The rate of total hemorrhage volume growth (hematoma plus IVH) among spot-positive subjects and ninety
day outcomes among spot positive subjects, dichotomized as modified Rankin Scale score of 0-4 versus 5-6,
comparing subjects treated with rFVIIa to those treated with placebo
Primary Outcome: Test Performance:
• The sensitivity and specificity of the spot sign for predicting hematoma growth.
Secondary Outcome: Test Performance:
• The positive and negative predictive values of the spot sign and the accuracy of the site investigators for
correct identification of the spot sign as compared to a blinded study neuroradiologist.
Analysis (Imaging):
The local investigator will use the baseline CT as part of the screening process for eligibility. Baseline
hematoma volume for study screening will be calculated by the ABC/2 method. De-identified baseline and 24hour CTs will be provided to the University of Calgary via the Clinical Coordinating Center for subsequent
interpretation by a blinded clinician. Hematoma volumes for study endpoints will be calculated by volumetric
analysis. Scans will also be analyzed for the location of hemorrhage, the presence and volume of IVH, the
presence or absence of hydrocephalus, edema volume, mass effect, prior infarction(s) (baseline CT) and acute
infarction(s).
Local investigators will interpret the CTA for the presence or absence of the spot sign in the acute setting.
Digital, de-identified copies of the CTAs will be provided to Sunnybrook Health Sciences Centre via the Clinical
Coordinating Center for subsequent interpretation by a blinded neuroradiologist. All CTAs will also be
subsequently reviewed for the presence or absence of the spot sign by a blinded study neurologist and a
blinded study emergency medicine physician. Measures of inter-rater reliability will be determined among the
evaluators, with the neuroradiologist’s reading considered the gold-standard.
Author Disclosure Block: M. Flaherty: Other Research Support; Significant; Novo Nordisk is supplying
study drug for this trial.
Presentation Number: CT P22
PI Coordinator Affiliation: University of Illinois at Chicago
PI Coordinator Name: Epideh Amin-Hanjani, MD FACS FAHA
Trial Abbreviation: VERiTAS
Trial Contact Information: Linda Rose-Finnell, [email protected], 312-355-2050
Trial Email: [email protected]
Trial Name: Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke
Trial Registry Number ID: NCT00590980
Trial Sponsor: NIH/NINDS
Trial Web Site: http://veritas.neur.uic.edu
Publishing Title: Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke
(VERiTAS) Study
Author Block: Sepideh Amin Hanjani, Keith Thulborn, Sean Ruland, Dilip Pandey, DeJuran Richardson,
Univ of Illinois at Chicago, Chicago, IL; Gregory J. Zipfel, Washington Univ Sch of Med at St. Louis, St. Louis,
MO; Mitchell S. Elkind, Columbia Univ, New York, NY; David S. Liebeskind, Univ of California at Los Angeles,
Los Angeles, CA; Jeffrey Kramer, Mercy Hosp and Medical Ctr, Chicago, IL; Frank Silver, Univ of TorontoToronto Western Hosp, Toronto, ON, Canada; Scott Kasner, Univ of Pennsylvania, Philadelphia, PR; Colin
Derdeyn, Washington Univ Sch of Med at St. Louis, St. Louis, MO; Philip B. Gorelick, Fady T. Charbel, Univ of
Illinois at Chicago, Chicago, IL
Abstract Body:
Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study
Background: Over one third of ischemic strokes occur in the posterior circulation, a leading cause of which is
vertebrobasilar occlusive disease secondary to atherosclerosis. Symptomatic vertebrobasilar disease (VBD)
carries a high annual risk of stroke, averaging 10-15% per year. Advances in endovascular angioplasty and
stenting have created new treatment options, but these interventions carry significant risks, and the selection
criteria for appropriate candidates remain uncertain. Determining predictors of stroke in this population is an
important step toward identifying those high risk patients most suitable for consideration of intervention.
Preliminary studies suggest that the risk of stroke in VBD is strongly related to the extent to which intracranial
blood flow is compromised.
Objective: To test the hypothesis that among patients with symptomatic VBD, those with distal blood flow
compromise, as determined by magnetic resonance (MR) blood flow imaging, are at higher risk of subsequent
posterior circulation stroke than those with normal flow.
Design: VERiTAS is a 5 year multicenter, prospective, observational cohort study, with a recruitment goal of
80 patients.
Population Studied: The target population is patients with symptomatic VBD. Inclusion criteria: stroke or
transient ischemic attack (TIA) in the vertebrobasilar territory; ≥ 50% stenosis or occlusion of extracranial or
intracranial vertebral or basilar arteries; symptoms within 60 days of enrollment; ≥ 18 years of age and ability to
provide informed consent. Exclusion criteria: major disabling stroke prohibiting the ability to return for follow-up
assessment; limited life expectancy; known cardiac disease associated with cardioembolic risk (e.g. atrial
fibrillation and prosthetic valves); blood dyscrasias; non-atherosclerotic vertebrobasilar disease (e.g.
dissection); unilateral vertebral stenosis or occlusion; inability to undergo MRI or cerebral angiography.
Study Procedures: Patients will undergo blinded hemodynamic assessment with MR based imaging,
consisting of quantitative MR angiography and MR perfusion, at enrollment and at 6 month intervals for at least
one year. Clinical assessments to identify recurrent ischemic events will be performed at routine intervals up to
two years maximum.
Outcome Measures: The primary endpoint is fatal and nonfatal ischemic stroke in the vertebrobasilar territory.
Analysis: Analysis of the primary endpoint will consist of time-to-event comparison using the log-rank test
between patients designated as 'low flow' versus 'normal flow' based upon the enrollment MR imaging.
Trial status: The study is open for enrollment at 6 sites (UIC, UCLA, Washington University, Columbia, Mercy,
UHN-Toronto Western Hospital). As of October 20, 2010, 40 subjects have been enrolled.
PI/Coordinator name: Sepideh Amin-Hanjani, MD
PI/Coordinator Affiliation(s): University of Illinois at Chicago
Trial Sponsor: NIH/NINDS
Trial Contact information: Linda Finnell, MPA, CCRA; 312-355-2050; [email protected]
Trial Email: [email protected]
Trial web site: http://veritas.neur.uic.edu
Author Disclosure Information:
Trial Name: Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke
Trial Abbreviation: VERiTAS Study
Trial Registry Number or 10: NCT00590980
PI/Coordinator Name(s): Sepideh Amin-Hanjani, MD
PI/Coord. Affiliation(s): University of Illinois at Chicago
Trial Sponsor(s): NINDS
Trial E-mail: [email protected]
Trial Web Site: http://veritas.neur.uic.edu
Trial Contact Information: Linda Rose-Finnell, [email protected], 312-355-2050
Author Disclosure Block: S. Amin Hanjani: Research Grant; Significant; NIH/NINDS. Other Research
Support; Modest; GE Healthcare, VasSol, Inc. K. Thulborn: Ownership Interest; Significant; Thulborn
Associates, Inc. (owner). S. Ruland: None. D. Pandey: None. D. Richardson: None. G.J. Zipfel: Research
Grant; Significant; NIH. Other Research Support; Modest; AHA, Brain Aneurysm Foundation, American Health
Assistance Foundation, Washington University ADRC. M.S. Elkind: None. D.S. Liebeskind: None. J.
Kramer: None. F. Silver: None. S. Kasner: None. C. Derdeyn: Research Grant; Significant; NIH/NINDS.
Honoraria; Modest; Synthes. Ownership Interest; Modest; nFocus, Inc.. Consultant/Advisory Board; Modest;
Pulse Therapeutics. Consultant/Advisory Board; Significant; W.L.Gore and Associates. P.B. Gorelick: Other
Research Support; Significant; Lundbeck, Inc. F.T. Charbel: Ownership Interest; Significant; VasSol, Inc..
Presentation Number: CT P23
PI Coordinator Affiliation: University of Edinburgh, University of Sydney
PI Coordinator Name: Peter Sandercock, Richard Lindley, Joanna Wardlaw
Trial Abbreviation: IST-3
Trial Contact Information: Peter sandercock: [email protected]
Trial Email: [email protected]
Trial Name: Third International Stroke Trial
Trial Registry Number ID: ISRCTN25765518
Trial Sponsor: University of Edinburgh and Lothian Health Board
Trial Web Site: http://www.ist3.com
Publishing Title: Third International Stroke Trial (IST-3) a Large-scale Randomised Controlled Trial Of
Thrombolytic Therapy For Patients With Acute Ischaemic Stroke ISRCTN ISRCTN25765518
Author Block: Peter A Sandercock, Univ of Edinburgh, Edinburgh, United Kingdom; Richard I Lindley, Univ
of Sydney, Sydney, Australia; Joanna Wardlaw, Univ of Edinburgh, Edinburgh, United Kingdom; The IST-3
collaborative group
Abstract Body:
Background. Current regulatory approvals permit the use of thrombolysis in a highly selected subset of patients
with acute ischaemic stroke. Objective. To determine whether a wider variety of patients can benefit from
treatment than is possible under the current approvals. Design. IST-3 is a randomised controlled, trial of iv rtPA (0.9mg/kg), with a PROBE (Prospective, Randomised, Open, Blinded Endpoint) design. Eligibility. acute
ischaemic stroke, assessed and able to start treatment within 6 hours of onset, CT (or MR) scan has excluded
intracranial haemorrhage. Details at www.ist3.com. Patient inclusion is by (telephone or a secure website to) a
rapid centralised randomisation system balancing on key prognostic factors. Treatment is allocated after the
baseline data have been recorded and cross-checked. Brain imaging (CT or MR) must be repeated after
treatment (at 24-48hrs). In centres where pre-treatment perfusion or angiography are routine, these scans are
collected as well the plain CT or MR scans. Baseline and follow-up CT/MR images reviewed by 'blinded' expert
panel. Perfusion and angiography data are processed centrally. In all centres, follow-up is conducted by
centralised (blinded) postal or telephone questionnaire, independently of the clinician treating the patient.
Outcome measures: primary outcome is survival free of death or dependence at six months. Planned subgroup
analyses: effect of: age, stroke severity, time to randomisation, blood pressure, CT appearances, perfusion or
angiographic findings (where available) on the risks and benefits of treatment. Sample size With 3100 patients,
the trial could detect a 4.7% absolute difference in the primary outcome. Trial Status: A total of 2444 patients
had been recruited by 13th October 2010. Results will be reported in May 2012.
Author Disclosure Block: P.A. Sandercock: Other; Modest; Member of independent DSMB for RELY trial.
R.I. Lindley: Speakers; Modest; Richard Lindley was supported to attend a national stroke meeting by
Boehringer Ingelheim and has also received honoraria for services as Scientific Committee member from the
company. J. Wardlaw: None.
Presentation Number: CT P24
PI Coordinator Affiliation: University of California, Irvine
PI Coordinator Name: Steven C. Cramer, MD
Trial Abbreviation: --Trial Contact Information: Steven C. Cramer, MD; [email protected]; FAX 714 456-8805; PHONE 714 4566876
Trial Email: [email protected]
Trial Name: A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating
Repeat Doses of GSK249320 in Patients With Ischemic Stroke
Trial Registry Number ID: Clinicaltrials.gov ID # NCT00833989
Trial Sponsor: GlaxoSmithKline
Trial Web Site: --Publishing Title: A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating
Repeat Doses of GSK249320 in Patients With Ischemic Stroke
Author Block: Steven C. Cramer, UC IRVINE MEDICAL CENTER, Orange, CA; On behalf of the
GSK249320 Study Investigators
Abstract Body:
BACKGROUND: There are no approved therapies for improving recovery post-stroke that are initiated beyond
the first few hours. Furthermore, in most studies where patients do receive an approved hyperacute stroke
therapy, most patients are left with significant disability despite overall efficacy. Therapies based on brain
repair have the potential to improve outcomes with a relatively wide time window. One such approach revolves
around promoting axon outgrowth and plasticity to augment brain repair. This is supported by studies that
indicate blocking myelin inhibitory proteins, such as myelin associated glycoprotein (MAG), improves outcome.
GSK249320 is a humanized IgG1 monoclonal antibody to MAG that has a disabled Fc region; these features
mitigate concerns related to (a) anti-MAG neuropathy, which is due to IgM-type antibodies, and (b) toxicity
caused by activation of Fc-effector functions for example, activation of the complement system due to C1q
binding. Studies in rodents and primates indicate that intravenous administration of GSK249320 beginning 24
hours after experimental stroke improves behavioral outcome, without changing infarct volume. GSK249320
appeared well-tolerated when administered to 31 healthy human subjects.
OBJECTIVE: The objective of this study is to evaluate the safety, pharmacokinetics, and pharmacodynamics of
various doses of GSK249320 in patients with recent stroke.
DESIGN: This is a placebo-controlled, randomized, single-blind, multicenter, international study.
POPULATION STUDIED: A total of 40 patients are planned for enrollment. Inclusion criteria include stroke
onset 24-72 hours prior to therapy initiation; the stroke must be radiologically confirmed to be either (a)
ischemic, supratentorial, and with diameter >15mm or volume >4cc, or (b) hemorrhagic, supratentorial, and
with an ICH score of 0-2; NIHSS score = 3-21; weakness in arm or leg or both; age 18-90 years; and
reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy. Exclusion
criteria include previous symptomatic stroke within 3 months prior to study entry; significant disability prior to
the current stroke; depression; significant aphasia; peripheral neuropathy; presence of neurological or
psychiatric disease likely to confound clinical evaluations; presence of a demyelinating disease; other major
chronic co-morbid conditions; contraindication to transcranial magnetic stimulation or MRI; participation in any
investigational rehabilitation paradigm targeting stroke recovery; or pregnancy or lactation.
INTERVENTION: Each patient will be randomized to receive 2 IV doses of either GSK249320 or placebo.
Dose 1 will be given 24-72 hr after stroke onset, and Dose 2 will be given 9+/- 1 days after Dose 1. There will
be three dose escalation cohorts (1, 5 and 15 mg/kg per dose), with 8 patients on placebo and 8 on active in
cohort 1 and 8 patients on active and 4 on placebo in cohorts 2 and 3. Doses will be given in a blinded fashion;
however study site pharmacy staff preparing infusions will be unblinded to patient treatment assignment.
OUTCOME MEASURES: The primary outcome measure is safety, as determined from adverse events, vital
signs, physical exam, ECG, nerve conduction tests, MRI, behavioral assessments, and laboratory testing.
Secondary outcome measures include immunogenicity, based on serum Ab measures; pharmacokinetics,
based on blood draws; function, based on behavioral assessments, both global and domain specific; and
neurophysiology, based on transcranial magnetic stimulation findings.
ANALYSIS: Adverse events and safety findings will be tabulated and examined. Estimates of the effect of
GSK249320 at each dose relative to placebo will be calculated for behavioral measures. The relationship
between GSK249320 plasma exposures and any markers of safety or biological activity will be subjected to
exploratory pharmacokinetic/pharmacodynamic analyses.
TRIAL STATUS: Fifteen sites in the US, Germany, and Canada are participating. As of October 13, 2010,
enrollment has completed with 42 patients enrolled. Follow up visits are ongoing.
Author Disclosure Block: S.C. Cramer: Research Grant; Significant; This study was supported by a grant
from GlaxoSmithKline. Consultant/Advisory Board; Significant; Dr. Cramer serves as a consultant to
GlaxoSmithKline.
Presentation Number: CT P25
PI Coordinator Affiliation: The NIHR Stroke Research Network
PI Coordinator Name: Prof Gary A. Ford
Trial Abbreviation: The NIHR Stroke Research Network Clinical Trials Portfolio
Trial Contact Information: [email protected]
Trial Email: n/a
Trial Name: The NIHR Stroke Research Network Clinical Trials Portfolio
Trial Registry Number ID: n/a
Trial Sponsor: n/a
Trial Web Site: n/a
Publishing Title: The National Institute of Health Research Stroke Research Network Clinical Trials Portfolio
Author Block: Gary A Ford, NIHR Stroke Res Network, Newcastle upon Tyne, United Kingdom; Philip M
Bath, Univ of Nottingham, Nottingham, United Kingdom; Martin M Brown, Univ Coll London, London, United
Kingdom; Ian Ford, Univ of Glasgow, Glasgow, United Kingdom; Anne Forster, Univ of Leeds, Leeds, United
Kingdom; Martin James, Royal Devon & Exeter Hosp, Exeter, United Kingdom; Kennedy R Lees, Matthew
Walters, Univ of Glasgow, Glasgow, United Kingdom; Sine Littlewood, NIHR Stroke Res Network, Newcastle
Univ, Newcastle upon Tyne, United Kingdom; Jonathan Mant, Univ of Cambridge, Cambridge, United
Kingdom; Hugh S Markus, St George's Univ of London, London, United Kingdom; Bogdan Milojkovic, NIHR
Stroke Res Network, Newcastle Univ, Newcastle upon Tyne, United Kingdom; Michael J Power, Ulster Hosp,
Belfast, United Kingdom; Sheila Lennon, Univ of Ulster, Co Antrim, United Kingdom; Chris Price, Wansbeck
General Hosp, Ashington, United Kingdom; Tom Robinson, Univ Hosp of Leicester NHS Trust, Leicester,
United Kingdom; Helen Rodgers, NIHR Stroke Res Network, Newcastle Univ, Newcastle upon Tyne, United
Kingdom; Christine Roffe, Keele Univ, Stoke-on-Trent, United Kingdom; Christopher R Burton, Bangor Univ,
Gwynedd, United Kingdom; Pippa Tyrrell, Univ of Manchester, Salford, United Kingdom; Marion F Walker, Univ
of Nottingham, Nottingham, United Kingdom
Abstract Body:
Background: The National Institute for Health Research (NIHR) Stroke Research Network (SRN) was
established in England in June 2005 to provide world-class health service infrastructure to support clinical
stroke research and remove barriers to its conduct. NIHR SRN facilitates stroke research through investment
in a national coordinating centre, 8 English local stroke research networks ($7 million funding in 2008), and
works closely with stroke research networks and structures in Scotland, Northern Ireland and Wales to
enhance clinical stroke research infrastructure, clinical co-ordination, research nursing staff, imaging and
pharmacy. In 2010 funding was provided to 8 Hyperacute Stroke Research Centres across England to support
the delivery of hyperacute stroke studies ($6 million funding over 3 years). NIHR SRN aims to increase
collaborative working between academics, stroke clinicians, patients and research funders. Support is provided
to academic studies funded through peer review and open national competition and commercial studies.
International studies funded in open national competition are potentially eligible for NIHR SRN support.
The UK wide study portfolio consisted of 88 open studies (51 randomized clinical trials, RCTs) in October 2010
with a further 11 studies in set-up. Patients recruited into stroke studies increased from 2598 (1941 in RCTs) in
2006/07 to 8734 (4893 in RCTs) in 2009/10 with patient recruitment from 191 hospitals. Increased recruitment
occurred in both academic and commercial funded studies and in all three areas of acute, rehabilitation and
prevention research.
The NIHR SRN portfolio includes the following academic and industry sponsored multi-centre international
trials open to recruitment:
CEPO, DIAS-4, SISTERS, T05018-1001, ACST-2, ARUBA, AVERT, CADISS, CLEAR III, CLOTS-3, ENOS,
EUPACT, INTERACT II, IRIS, IST-3, MASH-II, MISTIE, PODCAST, PRET, STASH, STICH II, VIST.
Investment in stroke clinical research infrastructure has had a major impact on UK stroke research activity.
Current activity suggests 5-6% of the incident UK stroke population participate in clinical stroke trials. The
future aims of SRN are to increase the number of patients participating in stroke studies in the UK to 10,000
each year with 7000 participating in randomised controlled trials. NIHR SRN welcomes applications from
academic chief investigators and commercial companies seeking support for UK patient recruitment to ongoing
clinical trials.
Author Disclosure Block: G.A. Ford: None. P.M. Bath: None. M.M. Brown: None. I. Ford: None. A.
Forster: None. M. James: None. K.R. Lees: None. M. Walters: None. S. Littlewood: None. J. Mant:
None. H.S. Markus: None. B. Milojkovic: None. M.J.P. Power: None. S. Lennon: None. C. Price: None. T.
Robinson: None. H. Rodgers: None. C. Roffe: None. C.R. Burton: None. P. Tyrrell: None. M.F. Walker:
None.
Presentation Number: CT P26
PI Coordinator Affiliation: Columbia University
PI Coordinator Name: Shunichi Homma
Trial Abbreviation: WARCEF
Trial Contact Information: Vilma Mejia (Asst. Project Manager), 630 West 168 St Mail Code 44, New York,
NY 10032 Tel # 212-305-3033
Trial Email: [email protected]
Trial Name: Warfarin versus Aspirin in Reduced Ejection Fraction
Trial Registry Number ID: NCT00041938
Trial Sponsor: NIH-NINDS
Trial Web Site: www.warcef.org
Publishing Title: Update on Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial
Author Block: J.L.P. Thompson, Shunichi Homma, Columbia Univ, New York, NY
Abstract Body:
Rationale and Design: Warfarin Aspirin Reduced Cardiac Ejection Fraction study (WARCEF) is a
randomized, double-blind, controlled trial comparing warfarin (INR= 2.75) and ASA (325mg) in patients with
reduced left ventricular ejection fraction (LVEF) in sinus rhythm.
Background: Patients with heart failure (HF) in sinus rhythm are at high risk of death, and have a 1.6%/ year
rate of stroke and 8-10% rate of recurrent stroke. Up to 28% of these patients are anticoagulated with warfarin
although no conclusive evidence identifies a preferred therapy. WARCEF is designed to assess whether
warfarin or ASA, in combination with current standard HF regimen, is superior for reducing the risk of death or
stroke in patients with reduced LVEF.
Methods: WARCEF is an NIH/NINDS-funded, NIH/NHLBI-endorsed multicenter randomized double-blind trial
involving 176 sites in11 countries. Patients in sinus rhythm with LVEF <35% (or wall motion index < 1.2) are
eligible. The target is 20% enrollment of patients with prior (<365 days) ischemic stroke or TIA. A maximum of
20% of enrolled patients may be NYHA Class I. The composite primary outcome is time to the first to occur of
death, ischemic stroke, or intracerebral hemorrhage (ICH). The trial was designed with 80% power with two
sided α=0.05 for any combination of the 3 component event rates that achieves the design hazard rate
reduction of 17.82% or more for either medication. Given recruitment curtailment, power for the primary
outcome is ≈65% for the design hazard rate reduction, and > 80% for the most important secondary outcome,
the first to occur of death, ischemic stroke, ICH, MI, or HF hospitalization. Safety is evaluated by assessing the
risk of major hemorrhagic and other serious adverse events. Given the greater costs and demands of warfarin
therapy, ASA will be declared preferable unless warfarin is found to be significantly superior on the primary
outcome.
Results: Recruitment ended in March 2010 with 2,305 patients randomized. Follow-up phase is ongoing until
May 2011.
Conclusions: No conclusive evidence identifies a preferred antithrombotic regimen for patients with low LVEF
in sinus rhythm. WARCEF is the only trial directly comparing anticoagulant and antiplatelet therapies in this
population. Any of the three possible outcomes (warfarin superior; ASA superior; neither superior) will lead to
an important treatment recommendation for patient care.
Author Disclosure Block: J. Thompson: None. S. Homma: None.
Presentation Number: CT P27
PI Coordinator Affiliation: University of California, San Diego
PI Coordinator Name: Patrick D. Lyden, MD
Trial Abbreviation: ICTuS 2/3
Trial Contact Information: [email protected]
Trial Email: [email protected]
Trial Name: The Intravascular Cooling in the Treatment of Stroke 2/3
Trial Registry Number ID: NCT01123161
Trial Sponsor: NINDS SPOTRIAS P50NS044148
Trial Web Site: http://clinicaltrials.gov/ct2/show/NCT01123161?term=ictus&rank=2
Publishing Title: Phase 2/3 Study of Intravenous Thrombolysis and Hypothermia for Acute Treatment of
Ischemic Stroke
Author Block: Thomas M Hemmen, Rema Raman, UCSD MEDICAL CENTER, San Diego, CA; David
Brown, Hoag Memorial Hosp Presbyterian, Newport Beach, CA; Fen-Lei Chang, Parkview Hosp, Fort Wayne,
IN; Gregor Broessner, Medische Univ Innsbruck, Innsbruck, Austria; Salvador Cruz-Florez, St Louis Univ, St
Louis, MO; Rainer Kollmar, Univsklinikum Erlangen, Erlangen, Germany; Gilda M Tafreshi, Scripps Mercy
Hosp, San Diego, CA; Mauricio Concha, Sarasota Memorial Hosp, Sarasota, FL; Irfan Altafullah, North
Memorial Hosp, Robbinsdale, MN; Patrick Michel, Univ de Lausanne, Lausanne, Switzerland; Sven Poli,
UnivsKlinikum Heidelberg, Heidelberg, Germany; Andrei V Alexandrov, Univ of Alabama, Birmingham, AL;
Karen S Rapp, UCSD MEDICAL CENTER, San Diego, CA; George A Lopez, James C Grotta, Univ of Texas
Medical Sch, Houston, TX; Patrick D Lyden, Cedars-Sinai Medical Ctr, Los Angeles, CA
Abstract Body:
Introduction: The purpose of this study is to determine whether the combination of thrombolysis and
hypothermia is superior to thrombolysis alone for the treatment of acute ischemic stroke. The study will be
conducted in two stages: a Phase 2 study to assess the safety of various protocol changes, to demonstrate
sufficient recruitment, and to allow an interim analysis for futility; a Phase 3 efficacy study will follow if prespecified milestones are achieved.
Methods: This is a prospective, randomized, single-blind, multi-center Phase 2/3 study. We aim to include
1600 ischemic stroke patients (400 in phase 2, 1200 in phase 3) treated within 3 hours of symptom onset with
IV tPA (according to FDA or EMEA protocol), NIHSS ≥7 and ≤20, age 22-80. Patients will be randomly
assigned to either hypothermia permissively targeted to 33ºC or normothermia. Favorable outcome is defined
as a 90-day Modified Rankin score (mRS) of 0 or 1. Secondary outcome measures are: 90-day NIHSS, Barthel
Index (BI), mortality, shift analysis of the mRS, global odds ratio of mRS, BI, NIHSS, incidence of symptomatic
intracranial hemorrhage and 90-day Montreal Cognitive Assessment. Interim analyses for futility are planned
after phase 2 and 800 patients, which include frequency of target temperature reached within 6 hours from
symptom, pneumonia rate, safety profile of iced saline infusion and study-wide average enrollment of at least
0.4 patients/site/month.
Status: The study team obtained a conditional IDE from the FDA. The sponsor, NINDS constituted a Data
Safety Monitoring Board and a study-wide safety physician was recruited to assist in study oversight. First
subject enrolment is planned for December 2010.
Sponsor: NINDS SPOTRIAS 3P50NS044227 and 5P50NS044148
Clinicaltrials.gov ID: NCT01123161
Cooling systems and catheters are provided by Philips/Innercool.
Author Disclosure Block: T.M. Hemmen: None. R. Raman: None. D. Brown: None. F. Chang: None. G.
Broessner: None. S. Cruz-Florez: None. R. Kollmar: None. G.M. Tafreshi: None. M. Concha: None. I.
Altafullah: None. P. Michel: None. S. Poli: None. A.V. Alexandrov: None. K.S. Rapp: None. G.A. Lopez:
None. J.C. Grotta: None. P.D. Lyden: None.
Presentation Number: CT P28
PI Coordinator Affiliation: University of Miami Miller School of Medicine
PI Coordinator Name: Myron D. Ginsberg, MD
Trial Abbreviation: ALIAS - Part 2
Trial Contact Information: ALIAS Part 2 Trial, [email protected], 305-243-6449
Trial Email: [email protected]
Trial Name: Albumin in Acute Stroke - Part 2
Trial Registry Number ID: NCT00235495
Trial Sponsor: NIH
Trial Web Site: https://webdcu.musc.edu/alias2/
Publishing Title: ALIAS-Part 2 Phase III Multicenter Clinical Trial of Albumin Therapy for Neuroprotection in
Acute Ischemic Stroke
Author Block: Myron D. Ginsberg, Univ of Miami Miller Sch of Med, Miami, FL; Michael D. Hill, Univ of
Calgary, Calgary, AB, Canada; Yuko Y. Palesch, Renee H. Martin, Sharon Yeatts, Medical Univ of South
Carolina, Charleston, SC; Claudia S. Moy, Natl Inst of Neurological Disorders and Stroke, Rockville, MD; Diego
Tamariz, Univ of Miami Miller Sch of Med, Miami, FL; Karla J. Ryckborst, Univ of Calgary, Calgary, AB,
Canada
Abstract Body:
Background
In extensive preclinical studies, human albumin conferred high-grade neuroprotection in focal cerebral
ischemia, with a therapeutic window extending to four hours.
An NIH-supported pilot-phase clinical trial of 25% human albumin (ALB) therapy in subjects with acute
ischemic stroke (duration =<16 h) was subsequently completed (Stroke 37:2100-6 and 37:2107-14, 2006). This
was a multiple-tier, dose-escalation safety trial comprising a standard-of-care IV tPA cohort (<3 h) and a nontPA cohort. Results: 82 subjects were enrolled (mean age 65 years; 52% male; 51% received tPA). Safety:
The only adverse event related to ALB therapy was mild-moderate pulmonary edema in 13% of subjects; this
was readily managed by furosemide, which was recommended prophylactically at the higher ALB dose-tiers.
Probing for efficacy: In the tPA cohort, 72% of subjects receiving ALB at dose-tiers IV-VI (average time 6.6 h
after stroke onset) had a favorable outcome at 3 months (defined as NIH Stroke Scale 0-1 and/or modified
Rankin Scale 0-1), compared to 36% of historical subjects who received tPA (but not ALB) in the NINDS tPA
Trial.
The NIH-funded ALIAS Phase III Multicenter Trial began subject enrollment in 2005. As of December 2007,
434 subjects had been enrolled at ~60 North American clinical sites. Mean age was 70 (SD 14, maximum 97);
mean time from stroke onset to study drug, 3.4 h (SD 0.7 h). Baseline NIHSS score was 13 (SD 6). Of these
subjects, 349 received thrombolysis. Neurological deterioration within 48 h occurred in 15%; death from any
cause within 90 days occurred in 17%; and pulmonary edema in 7.6%. In December, 2007, the DSMB placed
the trial on hold to review a safety concern. Revisions were then made to the protocol and analysis plan, and a
comprehensive site-training plan was constructed. The DSMB and NINDS then gave permission to re-start the
trial as “ALIAS Trial Part 2”.
Objective
The primary objective of ALIAS is to ascertain whether high-dose human ALB therapy (2.0 g/kg) increases the
proportion of acute ischemic stroke patients with favorable outcome compared to placebo therapy at 3 months
from randomization, as defined as NIH Stroke Scale score of 0-1 and/or modified Rankin Scale score of 0-1.
Design
ALIAS Part-1 was configured as two separate, concurrently implemented double-blinded, placebo-controlled,
multicenter Phase III clinical trials; separate randomization to ALB or placebo was carried out in a cohort
receiving standard-of-care thrombolysis and in a cohort not receiving thrombolytic therapy. By contrast, in the
currently ongoing ALIAS Part-2 Trial, these two cohorts are combined, and the primary analysis will adjust for
the effect of thrombolysis.
Study Population
ALIAS Part-2 requires a sample size of approximately 1,100 subjects, randomized 1:1 to ALB or placebo. This
sample size ensures 90% power in detecting an absolute treatment effect of 10% with alpha = 0.05, and
sufficient (80%) power to detect a thrombolysis x treatment interaction. Inclusion criteria in ALIAS Part-2: age
at least 18 and no older than 83 years (new in Part-2); baseline NIHSS score of 6 or greater; initiation of
ALB/placebo therapy within 5 h of stroke onset; and informed consent. Major exclusion criteria: congestive
heart failure (CHF), cardiac surgery or myocardial infarction in the previous 6 months; myocardial infarction or
CHF on admission; acute arrhythmia with hemodynamic instability; evidence of pulmonary edema; and acute
or chronic lung disease requiring O2 therapy. In Part-2, a normal serum troponin level is required for inclusion.
Intervention
Either ALB (25% solution; total dose 2.0 g/kg, not to exceed 750 ml) or saline solution is infused over 2 h. The
study drug infusion must start within 60 min of the start of thrombolysis or (in non-thrombolytic subjects) within
60 min of randomization. Other Protocol modifications in Part 2: A mandatory upper limit of 4,200 ml has been
imposed on the volume of IV fluids to be administered over the first 48 hours. Administration of a loop diuretic
(typically, furosemide 20 mg IV) is now mandatory between 12 and 24 hours after start of study-drug
administration. Reporting of IV fluid intake is mandatory during the first 48 h. More frequent cardiac monitoring
is required. Careful training and credentialing of all site investigators, sub-investigators, and coordinators is
emphasized.
Outcome Measures
Each subject is followed for one year. The primary efficacy outcome is assessed at 3 months at a clinic visit.
Brief (<30 minutes) telephone interviews for clinical and quality-of-life assessments are conducted at 1, 6, 9
and 12 months. Secondary analyses are conducted adjusting for possible confounding factors, using
generalized linear regression models.
Trial Status
ALIAS is being conducted at clinical sites throughout the United States and Canada, including sites
participating via the NIH-funded Neurological Emergencies Treatment Trials (NETT) Network. Approximately
75 sites are currently activated. Subject enrollment in ALIAS Part-2 began in February, 2009.
Author Disclosure Block: M.D. Ginsberg: Research Grant; Significant; NS40406. M.D. Hill: None. Y.Y.
Palesch: Research Grant; Significant; NS054630. R.H. Martin: None. S. Yeatts: None. C.S. Moy: None. D.
Tamariz: None. K.J. Ryckborst: None.
Presentation Number: CT P29
PI Coordinator Affiliation: National Stroke Research Institute
PI Coordinator Name: Julie Bernhardt
Trial Abbreviation: AVERT
Trial Contact Information: Principal Investigator, Julie Bernhardt, [email protected],
nsri.org.au/avert, fax +61394962650
Trial Email: [email protected]
Trial Name: A Very Early Rehabilitation Trial
Trial Registry Number ID: ACTRNO1260600185561
Trial Sponsor: NHMRC, Stroke Association UK, Chest Heart and Stroke Scotland, Northern Ireland Chest
Heart and Stroke, Signapore Health
Trial Web Site: www.nsri.org.au/AVERT
Publishing Title: A Very Early Rehabilitation Trial (AVERT): Ongoing Phase III Trial of Efficacy and Cost
Effectiveness of Early Mobility Training after Stroke
Author Block: Julie Bernhardt, Natl Stroke Res Inst, Heidelberg Heights, Australia; on behalf of the AVERT
Trialist Collaboration
Abstract Body:
Introduction: Getting patients out of bed very early after stroke (<24 hours) may be an important component
of effective stroke unit care but this requires testing in a randomized controlled trial. We hypothesize that very
early and frequent mobilization (VEM) will reduce death and disability and be cost effective. Methods: Study
design: Phase III, international, multi-centre, single-blind, randomized controlled trial. Inclusion criteria: Patients
over 18 years, admitted within 24 hrs of confirmed cerebral infarct or haemorrhage, whose physiological
parameters fall within set limits. Exclusion Criteria: Patients with severe premorbid disability, severe
comorbidities or requiring palliative care. Treatment with rtPA is not an exclusion. Randomisation: Web-based,
blocked randomisation by site and stroke severity (NIHSS). Intervention: The VEM protocol, delivered by a
nurse/physiotherapy team, begins within 24hrs of stroke and continues at least twice daily for up to 14 days.
Control patients receive standard care. Primary outcome is modified Rankin Scale at 3 months. Sample size is
2104 patients (n=1052 per group). Analyses will be intention to treat. A cost effectiveness analysis forms part
of the study design. Safety outcomes: Deaths and serious adverse events (SAEs), including serious falls, at 3
months are extracted from the medical record by a blinded assessor. Results: Phase III commenced in July
2006 in 7 sites in Australia but the trial has now expanded to include 37 sites from 5 countries (Australia, New
Zealand, Malaysia, Singapore and UK), with further UK expansion planned for 2011. At October 2010, 823
patients have been recruited, with a current average recruitment rate of 30 patients per month. The proportion
of screened versus recruited patients ranges from 1.4% - 19.0% (mean 6.4%) across sites. Mean age is 70.5
years (SD 13.1), 80.2% with first ever stroke, 86.4% infarct, mean NIHSS score of 9.3 (SD 6.8) at time of
randomization 17 (SD 5.9) hours post stroke. Almost half of our patient sample (48.0%) have an NIHSS > 7
(moderate and severe stroke) . To date 140 patients (17.0%) have been treated with rtPA. Sixty one patients
(8.3%) have died within 3 months of stroke, and there have been only 7 drop outs (<1% of patients). In
conclusion, the trial is progressing well. Recent expansion of trial sites should see recruitment completed by
end of 2012.
Author Disclosure Block: J. Bernhardt: Research Grant; Modest; National Health and Medical Research
Council Grant funds this project.
Presentation Number: CT P30
PI Coordinator Affiliation: Klikikum Coburg
PI Coordinator Name: Johannes Brachmann
Trial Abbreviation: CRYSTAL-AF
Trial Contact Information: Frank Beckers
Trial Email: [email protected]
Trial Name: Cryptogenic Stroke and Underlying Atrial Fibrillation Trial
Trial Registry Number ID: NCT00924638
Trial Sponsor: Medtronic, Inc.
Trial Web Site: http://clinicaltrials.gov/ct2/show/NCT00924638?term=CRYSTAL-AF&rank=1
Publishing Title: Cryptogenic Stroke And Underlying Af Trial (crystal Af): Design, Status And Clinical
Significance To Patients, Physicians, And Hospitals
Author Block: Richard A Bernstein, Northwestern Univ, Glenview, IL; Johannes Brachmann, Klinikum
Coburg, Coburg, Germany; Hans-Christoph Diener, Univ Hosp Essen, Essen, Germany; Carlos A Morillo MD,
McMaster Univ, Hamilton, ON, Canada; Tommaso Sanna MD, Vincenzo DiLazzaro MD, Catholic Univ of the
Sacred Heart, Rome, Italy; Rod Passman, Northwestern Univ, Chicago, IL; Marilyn Rymer, St Lukes Hosp,
Kansas City, MO
Abstract Body:
Background:
Stroke is the third leading cause of mortality in the US and the leading cause of long-term disability. Stroke of
undetermined cause (cryptogenic) accounts for approximately 25-30% of ischemic strokes and it is assumed
that asymptomatic paroxysmal atrial fibrillation (AF) may be an important underlying cause.
The American and European stroke guidelines recommend patients with cryptogenic stroke to take
antiplatelets for secondary stroke prevention (stroke recurrence). However, when a stroke patient is found to
have AF, the guidelines recommend anticoagulation due to its superior efficacy over antiplatelets for stroke
prevention. Several studies have shown that oral anticoagulation reduced the risk of stroke in AF patients by
up to 80%. Stroke in combination with AF is associated with greater disability and mortality than in the absence
of AF. It is thus clinically important to detect underlying AF. The technologies currently used to identify
episodes of AF appear to be inadequate.
The CRYSTAL AF study seeks to provide clinical evidence, demonstrating that long term monitoring by the
Reveal XT insertable cardiac monitor in patients with cryptogenic stroke has AF diagnostic superiority
compared to usual care and to investigate the true incidence of AF in this population.
Study design:
CRYSTAL AF is a 1:1 randomized, prospective, multicenter study in which approximately 450 patients will be
included in about 60 active sites in Europe, US and Canada. Patients are eligible for inclusion after diagnosis
of cryptogenic stroke or Transient Ischemic Attack (TIA). Each patient will be followed until study closure with a
minimum of 12 months.
Objectives: The primary objective is the time to first documented event of AF by 6 months of continuous rhythm
monitoring versus standard arrhythmia diagnostics in subjects with a recent cryptogenic stroke or TIA without
previously documented history of AF. The most important secondary objective is the time to first documented
AF event by 12 months of continuous rhythm monitoring. Other secondary objectives are:
- To compare the incidence of recurrent stroke or TIA in patients with a recent cryptogenic stroke or TIA
randomized to long-term rhythm monitoring versus standard of care treatment.
- To compare the change, and reasons for change, in use of oral anticoagulation and anti-arrhythmic drugs
over time in both arms.
- To compare the hazard rate for the amount and duration of cardiovascular related hospitalization in both arms
- To describe health outcomes, economic and clinical disease burden and the care pathways of enrolled
patients
- To evaluate the role of the Patient Assistant device in time to diagnosis in patients implanted with the Reveal
XT. The patient follow-up in the Reveal implanted arm will use CareLink remote monitoring system.
Current status:
As of 26 October 2010, there were 39 centers enrolling 129 patients in the study.
Study milestone schedule:
Data collection will be closed 12 months after enrollment of the last patient. The study enrolled the first patient
on 17 June 2009 and a publication is expected in early 2013.
Author Disclosure Block: R.A. Bernstein: Research Grant; Modest; Medtronic. Speakers; Modest;
Medtronic. Consultant/Advisory Board; Modest; Medtronic. J. Brachmann: None. H. Diener: None. C.A.
Morillo: None. T. Sanna: None. V. DiLazzaro: None. R. Passman: None. M. Rymer: None.
Presentation Number: CT P31
PI Coordinator Affiliation: University of Nottingham, United Kingdom
PI Coordinator Name: Professor Philip Bath
Trial Abbreviation: ENOS
Trial Contact Information: Mrs Sally Utton/[email protected] /Tel: +44 (0)115 82 30287/Fax: +44
(0)115 82 31771
Trial Email: [email protected]
Trial Name: Efficacy of Nitric Oxide in Stroke
Trial Registry Number ID: ISRCTN99414122
Trial Sponsor: University of Nottingham, United Kingdom
Trial Web Site: www.enos.ac.uk
Publishing Title: Efficacy of Nitric Oxide in Stroke (ENOS) Trial - A Prospective Randomised Controlled Trial
in Acute Stroke
Author Block: Sandeep Ankolekar, Cheryl Hogg, Sally Utton, Philip M Bath, Univ of Nottingham, Nottingham,
United Kingdom
Abstract Body:
Rationale: Acute hypertension is associated with a poor outcome after stroke. No large trials have assessed
the effect of altering BP during the acute phase of stroke on outcome. We are testing whether nitric oxide, a
multimodal molecule given as glyceryl trinitrate (GTN), is safe and effective in improving outcome after acute
stroke. Furthermore, around half of all patients admitted with acute stroke are taking antihypertensive therapy
immediately prior to the stroke. No data exist as to whether it is beneficial or safe to stop or continue this
treatment during the acute phase.
Design: ENOS is a prospective, international, multicentre, randomised, parallel-group, blinded, controlled trial.
5,000 ischaemic or haemorrhagic stroke patients with systolic BP 140-220 mmHg, and within 48 hours of onset
will be included. Subjects will be randomised to 7 days of single-blind treatment with transdermal GTN or
control. Those patients taking prior antihypertensive therapy will also be randomised to continue or temporarily
stop this for 7 days. ENOS is conducted over a secure internet site. The primary outcome is modified Rankin
Scale at 90 days which is carried out by a blinded assessor. The analysis will be by intention to treat.
Trial status: As at 28th October, 2010, 2043 patients had been recruited from 116 centres (Australia, Canada,
China, Egypt, Hong Kong, India, Italy, Malaysia, New Zealand, Philippines, Poland, Republic of Ireland,
Romania, Singapore, Spain, Sri Lanka and UK). More centres welcome to join.
Author Disclosure Block: S. Ankolekar: None. C. Hogg: None. S. Utton: None. P.M.W. Bath: None.
Presentation Number: CT P32
PI Coordinator Affiliation: UCLA Stroke Center
PI Coordinator Name: Jeffrey Saver, MD (not PI- Stroke CDE Working Group Chair)
Trial Abbreviation: NINDS CDE Project
Trial Contact Information: [email protected]
Trial Email: [email protected]
Trial Name: National Institute of Neurological Disorders and Stroke Common Data Element Project
Trial Registry Number ID: N/A
Trial Sponsor: NINDS, NIH
Trial Web Site: http://www.commondataelements.ninds.nih.gov/
Publishing Title: Version 1.0 of the Stroke Common Data Elements Available for Public Use from the National
Institute of Neurological Disorders and Stroke, National Institutes of Health Common Data Element Project
Author Block: Lisa Hunegs, Stacie Grinnon, KAI Res, Inc., Rockville, MD; Joanne Odenkirchen, Natl Inst of
Neurological Disorders and Stroke (NINDS), Rockville, MD
Abstract Body:
Rationale: To assist investigators conducting clinical studies and accelerate data sharing, the NINDS with its
contractor, KAI Research, Inc., continues to foster its Common Data Element (CDE) Project. At the past two
International Stroke Conferences, the Project convened a Working Group of experts in stroke clinical research
to advise the Institute on the development of Stroke CDEs and accompanying resources.
Methods: The sixty-three member Stroke CDE Working Group (WG) divided into subgroups who met
periodically to identify and define elements for nine specific domains of data (e.g., stroke types and subtypes;
outcomes and endpoints; etc.). After each subgroup identified and defined elements for their domain, they
vetted their recommendations through the entire WG. The recommendations include the following:
• Catalog of approximately 600 Stroke CDEs with detailed specifications for each CDE;
• List of approximately 35 standardized instruments with explanations of when each instrument is
recommended for use.
A beta version of the Stroke CDEs was posted to the CDE Web site
(http://www.commondataelements.ninds.nih.gov/) for public review in August 2010. During this one-month
review period, select organizations and the larger research community were asked to review the CDEs and
provide feedback about their utility. The Working Group is currently addressing the feedback. By the end of
November 2010, Version 1.0 of the Stroke CDEs will be published on the Web site for public use.
Results: The poster presentation will provide an update about the status of the Stroke CDEs, including:
• Report of those researchers who have already begun to use the Stroke CDE;
• Examples of how user feedback was used to improve the Stroke CDEs;
• Explanation of how the Stroke CDEs can be used by a clinical study; and
• Next steps to ensure the Stroke CDEs meet the evolving needs of stroke researchers.
Conclusions: The NINDS recognizes that the best way to ensure the Stroke CDEs are useful tools and the
CDE Project accomplishes its goals is to continuously revise and add to the CDEs based upon the feedback of
researchers. Thus, the Institute strongly encourages investigators conducting clinical research studies to use
the CDEs and welcomes users to submit feedback regarding its CDEs through the CDE Web site.
Author Disclosure Block: L. Hunegs: None. S. Grinnon: None. J. Odenkirchen: None.
Presentation Number: CT P33
PI Coordinator Affiliation: Georgetown University/National Rehabilitation Hospital
PI Coordinator Name: Alexander W. Dromerick MD/Chelsea S. Kidwell MD/Deeonna Farr MPH
Trial Abbreviation: PROTECT DC
Trial Contact Information: Deeonna Farr MPH, [email protected]
Trial Email: [email protected]
Trial Name: Preventing Recurrence of Thromboembolic Events through Coordinated Treatment in the District
of Columbia
Trial Registry Number ID: NCT00703274
Trial Sponsor: NINDS U54 057405
Trial Web Site: http://clinicaltrials.gov/ct2/show/NCT00703274?term=protect+dc&rank=1
Publishing Title: A Phase II RCT of Stroke Navigators to Improve Compliance with Secondary Stroke
Prevention: PROTECT DC
Author Block: Alexander W Dromerick, Natl Rehabilitation Hosp, Washington, DC; M. Christopher Gibbons,
Johns Hopkins Sch of Med, Baltimore, MD; Dorothy F Edwards, Univ of Wisconsin, Madison, WI; Deeonna
Farr, Natl Rehabilitation Hosp, Washington, DC; Annapurni Jayam-Trouth, Howard Univ Sch of Med,
Washington, DC; Nawar M Shara, Georgetown Univ/Medstar Health Res Inst, Washington, DC; Brisa M
Sanchez, Univ of Michigan, Ann Arbor, MI; Ali Fokar, Medstar Health Res Inst, Hyattsville, MD; Regina Coles,
Georgetown Univ, Washington, DC; Judson D Richardson, Natl Rehabilitation Hosp, Washington, DC; Bruce
Ovbiagele, UCLA Sch of Med, Los Angeles, CA; Chelsea S Kidwell, Georgetown Univ, Washington, DC
Abstract Body:
Trial Abbreviation: PROTECT DC
Trial Registry Number: NCT00703274
Background: Despite significant advances in the prevention and treatment of cerebrovascular disease, stroke
remains the third leading cause of death and a leading cause of adult disability. The initiation of effective
secondary prevention strategies is most effective when implemented early (before disabling stroke occurs),
monitored frequently, and maintained long-term after a cerebrovascular event. PROTECT DC facilitates the
initiation of secondary prevention behaviors in an attempt to prevent the recurrence of stroke among
participants. The program trains a lay person, called a stroke navigator, to provide participants with education
on secondary prevention behavior and to navigate the health and human service system, which will assist
participants in obtaining the necessary services and programs to engage in secondary prevention behaviors.
Population (n=250):
1. Age ≥ 18 years
2. Hospitalized due to ischemic stroke or intercurrent ischemic stroke event within the past 30 days
3. Large vessel, small vessel, or cryptogenic with stroke risk factor etiologies as defined by TOAST criteria
4. Community dwelling prior to stroke
5. Resides within the District of Columbia or closely in its suburbs
6. Expected to reside after hospital discharge within the District of Columbia or closely in its suburbs
7. Caregiver or interested party available, if moderately or severely disabled (not required to actually reside
with participant)
8. Sufficient number of collateral contacts to assure follow-up.
9. NIHSS <20
Objective: To determine whether stroke navigators can improve compliance with secondary stroke prevention
measures in an urban underserved population with atherogenic ischemic stroke.
Design: Phase II, single-blind, randomized controlled trial
Interventions:
Experimental: Stroke navigation for a one year period.
Control: Usual and customary care for one year
Outcome Measures:
Primary: Composite score of compliance with objective measures of risk factor control (e.g. systolic blood
pressure, HbA1c, LDL, INR, antithrombotic pill count) at one year after stroke onset.
Secondary: Stroke knowledge, exercise, dietary modification, smoking cessation at one year.
Analysis: Intention to treat
Trial status: Actively enrolling since July 1, 2008; As of October 15, 2010, 150 of the target 250 participants
have been enrolled, with 75 randomized to the experimental condition and 75 randomized to the control
condition. Thus far, 73 participants have completed the primary 1-year time point. Mean age of the enrolled
participants is 61 years (SD=12, range 33 - 90), 91% are African-American, 44% are male and the median
NIHSS score is 3 (range 0 - 16).
PI/Coordinator Name: Alexander W. Dromerick MD/Chelsea S. Kidwell MD/Deeonna E. Farr MPH
PI/Coordinator Affiliation: Georgetown University/National Rehabilitation Hospital
Trial Sponsor: National Institute of Neurological Disorders and Stroke
Contact Information: [email protected]; Voice: 202-877-1931
Author Disclosure Block: A.W. Dromerick: None. M.C. Gibbons: None. D.F. Edwards: None. D. Farr:
None. A. Jayam-Trouth: None. N.M. Shara: None. B.M. Sanchez: None. A. Fokar: None. R. Coles:
None. J.D. Richardson: None. B. Ovbiagele: None. C.S. Kidwell: None.
Presentation Number: CT P34
PI Coordinator Affiliation: University of Cincinnati
PI Coordinator Name: Arthur M. Pancioli, MD
Trial Abbreviation: The CLEAR-ER Stroke Trial
Trial Contact Information: Pamela A. Schmit RN BSN [email protected] 513-558-6142
Trial Email: [email protected]
Trial Name: The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke
Enhanced Regimen
Trial Registry Number ID: P50-NS044283
Trial Sponsor: NINDS
Trial Web Site: www.clear-er.org
Publishing Title: The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke
Enhanced Regimen (The CLEAR-ER Stroke Trial): An Ongoing Phase IIb Trial
Author Block: Arthur M. Pancioli, U CINCINNATI MEDICAL CTR, Cincinnati, OH; for the CLEAR-ER
Investigators
Abstract Body:
INTRODUCTION AND HYPOTHESIS:
The CLEAR-ER trial is a NIH-funded, Phase IIb, randomized, multi-center, double-blind, controlled trial of the
combination of medium dose rt-PA plus eptifibatide versus standard dose rt-PA in acute ischemic stroke
patients that can have rt-PA treatment begun within 3 hours of symptom onset.
METHODS:
A total of 126 subjects with a NIHSSS> 5 will be enrolled over the next 3 years at 10 centers in the United
States. Patients are randomized to a combined intravenous medium-dose rt-PA (0.6mg/kg, 60 mg max) and
eptifibatide (135 mcg/kg IV bolus and a 2 hour infusion of 0.75 mcg/kg/min) or standard dose (0.9 mg/kg, 90
mg max, 10% as bolus) rt-PA in a 5 to 1 ratio. This will result in a total of 105 patients treated with the
combined regimen, and 21 patients treated with standard dose IV rt-PA alone. The primary safety outcome
measure is symptomatic ICH within 36 hours of initiation of therapy. The study will determine if there is a signal
of efficacy such that a Phase III Trial of this combination is warranted. The primary measure of clinical outcome
is the percentage of patients meeting a modified Rankin Scale score of 0 or 1 or return to their baseline at 90
days post treatment.
CONCLUSIONS: The CLEAR-ER Trial will obtain reliable estimates of the safety of an enhanced dosing
regimen of eptifibatide in combination with medium-dose rt-PA in acute stroke patients in whom treatment is
begun within three hours of onset. As of November 1, 2010, 39 subjects have been randomized into the trial.
Author Disclosure Block: A.M. Pancioli: Research Grant; Significant; NINDS, EKR Therapeutics. Other
Research Support; Significant; Genentech, Schering Plough. Consultant/Advisory Board; Modest; NTI.
Presentation Number: CT P35
PI Coordinator Affiliation: University of Edinburgh
PI Coordinator Name: JM Wardlaw, PAG Sandercock, RI Lindley
Trial Abbreviation: IST3 Perfusion+Angiography Study
Trial Contact Information: Joanna Wardlaw, Department of Clinical Neurosciences, Western General
Hospital, Edinburgh EH4 2XU, United Kingdom. Fax ++ 44 (0)131 332 5150 email: [email protected]
Trial Email: [email protected]
Trial Name: Third International Stroke Trial Perfusion and Angiography Study
Trial Registry Number ID: ISRCTN25765518
Trial Sponsor: University of Edinburgh and NHS Lothian, co-sponsors
Trial Web Site: www.ist3.com
Publishing Title: The Third International Stroke Trial (IST-3) A Large Randomised Controlled Trial of rt-PA in
Acute Ischemic Stroke: Perfusion and Angiography Study: Current Progress and Recruitment
Author Block: Joanna Wardlaw Sr., Peter Sandercock Sr, Trevor Carpenter Jr, Univ of Edinburgh,
Edinburgh, United Kingdom; Rudiger von Kummer Sr, Univ of Dresden, Dresden, Germany; Anders von Heijn,
Veronica Murray, Karolinska Inst, Stockholm, Sweden; Andre Peeters, St Luc Hosp, Louvain, Belgium; Mark
Parsons, John Hunter and Calvary Mater Hosp, Newcastle, Australia; Adam Kobayashi, Univ of Warsaw,
Warsaw, Poland; Max Wintermark, Univ of Virginia, Charlottesville, VA; Richard Lindley, Univ of Sydney,
Sydney, Australia; IST3 Perfusion and Angiography Study Group
Abstract Body:
Background: MR and CT Perfusion (MRP, CTP) and Angiography (MRA, CTA) are used increasingly in
clinical practice but their role in stroke diagnosis and to guide thrombolytic therapy remains unclear. Opinion on
which perfusion parameter to use and whether only patients with an occluded artery or perfusion deficit should
receive rt-PA varies widely.
Objective: To determine the effect of rt-PA 0.9mg/kg on lesion growth and functional outcome in the
presence/absence of a perfusion deficit or occluded artery and which perfusion parameter best predicts lesion
growth and functional outcome.
Study Design: IST-3 is a randomised controlled trial of rt-PA given up to six hours after acute ischemic stroke
with blinded prospective outcome assessment. CTP/MRP and/or CTA/MRA are acquired at randomisation
and/or 24 hours after trial treatment.
Eligibility: Patients with acute ischemic stroke (CT or MR imaging having excluded hemorrhage) who can start
treatment within 6 hours of stroke. No definite indication for rt-PA, perfusion or angiography imaging. No
contraindication to rt-PA, contrast agents or MR imaging.
Trial procedures: In addition to those of IST3 core trial, patients have CTP/MRP and/or CTA/MRA pre and/or
24 hours post rt-PA treatment. Data are analysed centrally using dedicated software.
Trial outcome measures: Infarct growth from pre-randomisation to 24 hours; functional outcome on the
modified Rankin Scale at 6 months; hemorrhagic transformation.
Sample size: At 80% power (alpha of 0.05) 100 patients would detect a 27% difference and 400 a 15%
difference in infarct growth between patients allocated rt-PA and control according to perfusion defect or
arterial occlusion. We aim to recruit a total of 300 patients.
Analysis: 12 quantitative and qualitative perfusion parameters and thresholds are being assessed with
bespoke and commercial software. Arterial patency is quantified using TIMI and MORI scores. Analysis will
adjust for patient, image, and stroke variables.
Trial Status: 45 centres in 10 countries are participating. The IST3 Perfusion and Angiography study has
perfusion data on 104 patients from 21 centres (mostly CTP) and angiography data from 29 centres on 221
patients (mostly CTA). Recruitment continues until 30th June 2011. The results will be reported in 2012.
Author Disclosure Block: J. Wardlaw: Research Grant; Significant; EME study funding, MRC trial funding.
P. Sandercock: ; EME study funding, MRC trial funding. T. Carpenter: ; EME study funding. R. von Kummer:
None. A. von Heijn: None. V. Murray: None. A. Peeters: None. M. Parsons: None. A. Kobayashi: None. M.
Wintermark: None. R. Lindley: None.
Presentation Number: CT P36
PI Coordinator Affiliation: Massachusetts General Hospital
PI Coordinator Name: Albert Yoo, MD
Trial Abbreviation: PICS
Trial Contact Information: Siu Po Sit, PhD, [email protected], 510-748-3221
Trial Email: [email protected]
Trial Name: Penumbra Imaging Collaborative Study
Trial Registry Number ID: NCT00785161
Trial Sponsor: Penumbra, Inc.
Trial Web Site: www.penumbrainc.com
Publishing Title: Final (post-treatment) ASPECTS Score Is An Independent Predictor Of Clinical Outcome
Following Endovascular Treatment Of Acute Anterior Circulation Ischemic Stroke: Analysis Of The PICS
Database
Author Block: Albert Yoo, Massachusetts General Hosp, Boston, MA; Michael Brant-Zawadzki, Hoag Hosp,
Newport Beach, CA; Donald Frei, Swedish Medical Ctr, Englewood, CO; Donald Heck, Forsyth Medical Ctr,
Winsten-Salem, NC; Tim Malisch, Alexian Brothers Medical Ctr, Elk Grove Village, IL; Sean Meagher, OSF
Saint Francis Medical Ctr, Peoria, IL; Darryn Shaff, Lehigh Valley Health Network, Allentown, PA; Benjamin
Crandall, Abbott Northwestern Hosp, Minneapolis, MN; Osama Zaidat, Medical Coll of Wisconsin, Milwaukee,
WI; Michael Alexander, Cedars-Sinai Medical Ctr, Los Angeles, CA; Laszlo Miskolczi, Holy Cross Hosp, Fort
Lauderdale, FL; Brian Chong, Mayo Clinic, Phoenix, AZ; Robert Tarr, Univ Hosp of Cleveland, Cleveland, OH;
Aaron Daniel Sasson, Maimonides Medical Ctr, Brooklyn, NY; Avi Setton, North Shore Univ Hosp, Manhasset,
NY; Aquilla Turk III, MUSC, Charleston, SC; Christopher Zylak, Sacred Heart Medical Ctr, Spokane, WA; R.
Gilberto Gonzalez, Zeshan A. Chaudhry, Massachusetts General Hosp, Boston, MA; Elan Mualem, Penumbra,
Inc, Alameda, CA; Arani Bose, Siu Po Sit, Penumbra, Inc., Alameda, CA; For the PICS Investigators
Abstract Body:
Purpose: Preliminary data suggests that pre-treatment ASPECTS score predicts the clinical response to
reperfusion in patients with anterior circulation proximal artery occlusions (PAO) treated with endovascular
therapy. We sought to validate the clinical importance of ASPECTS-determined infarct size in this patient
population by analyzing final infarct extent using post-treatment imaging.
Methods: PICS is a prospective multicenter registry of clinical and imaging data in PAO patients treated with
the Penumbra Stroke System. Anterior circulation stroke patients were identified for inclusion into this analysis.
ASPECTS scores were determined by a central core imaging laboratory on available pre-treatment (pre-) CT
scans and post-treatment (post-) CT and MRI studies. Imaging analysis was performed blinded to all clinical
data, except stroke side. Statistical analysis was performed to determine the clinical and imaging predictors of
functional outcome. Variables with a univariate p-value <0.2 were included in a multivariate model. Statistical
significance was considered at p<0.05.
Results: A total of 102 anterior circulation PAO patients were identified, which included 55 (53.9%) left-sided
strokes and 56/101 (55.4%) females. The mean age was 66.0 ± 15.8 years; the median NIHSSS was 16.0
(IQR 12-22). The mean time from stroke onset to presentation was 3.0 ± 3.5 hours. The mean time from groin
puncture to termination of thromboaspiration was 91.4 ± 54.3 minutes. The rate of TIMI 2/3 revascularization
was 83.3%. Thirty-nine (38.2%) patients achieved 90-day mRS 0-2, and 22 (21.6%) patients died.
The median pre-ASPECTS score (n=92) was 8.0 (IQR 7-10), and median post-ASPECTS score (n=67) was
6.0 (IQR 5-8). Patients with good clinical outcome (mRS 0-2) had a higher median post-ASPECTS score than
those with mRS 3-6 (7 [IQR 6-8] versus 5 [IQR 4-7]; p=0.01). In Receiving Operating Characteristic (ROC)
analysis, a post-ASPECTS threshold of >5 optimized sensitivity and specificity for good outcome. Among
patients with post-ASPECTS >5, 53.7% (22/41) had a good outcome, compared with 20.0% (5/25) of patients
with post-ASPECTS ≤5 (p=0.01). In multivariate analysis, only post-ASPECTS >5 (OR 5.77, p=0.005) and age
<80 (OR 4.65, p=0.02) were independent predictors of good outcome (Table).
Reperfusion status was the best predictor of the change in ASPECTS between pre-and post-treatment scans
(multivariate p=0.049). Patients with TIMI 2-3 revascularization had a smaller median decrease in ASPECTS
(less infarct growth; 2 [IQR 0-3] vs. 3 [IQR 1.5-6], p=0.08) and higher post-ASPECTS scores (6 [IQR 5-8] vs. 4
[IQR 3-7], p= 0.04) compared to those without reperfusion, despite similar pre-ASPECTS scores (median of 8
for both).
Conclusions: Final infarct size quantified using ASPECTS is an important determinant of clinical outcome
following endovascular stroke therapy. Reperfusion limits infarct growth between the pre- and post-treatment
ASPECTS.
Author Disclosure Block: A. Yoo: Research Grant; Significant; Penumbra, Inc. M. Brant-Zawadzki:
Honoraria; Modest; Penumbra, Inc. D. Frei: ; Penumbra, Inc. D. Heck: ; Penumbra, Inc. T. Malisch: ;
Penumbra, Inc.. S. Meagher: None. D. Shaff: None. B. Crandall: None. O. Zaidat: ; Penumbra, Inc.. M.
Alexander: None. L. Miskolczi: None. B. Chong: None. R. Tarr: None. A.D. Sasson: None. A. Setton:
None. A. Turk: ; Penumbra, Inc.. C. Zylak: None. R. Gonzalez: None. Z.A. Chaudhry: None. E. Mualem:
Employment; Significant; Penumbra, Inc. A. Bose: ; Penumbra, Inc. S. Sit: ; Penumbra, Inc..
Presentation Number: CT P37
PI Coordinator Affiliation: TBD
PI Coordinator Name: TBD
Trial Abbreviation: None
Trial Contact Information: Pfizer CT.gov Call Center 1-800-718-1021
Trial Email: TBD
Trial Name: A Phase 2 Multicenter, Randomized, Double-blind, Placebo Controlled Study of the Safety and
Efficacy of PF-03049423 in Subjects with Ischemic Stroke
Trial Registry Number ID: NCT01208233
Trial Sponsor: Pfizer Inc
Trial Web Site: www.clinicaltrials.gov ID # NCT01208233
Publishing Title: A Phase 2 Multicenter, Randomized, Double-blind, Placebo Controlled Study of the Safety
and Efficacy of PF-03049423 in Subjects with Ischemic Stroke
Author Block: Martin M Bednar, Pfizer Inc, Groton, CT; Steven C Cramer, U. California, Irvine, CA; Seth P
Finklestein, Biotrofix Inc, Waltham, MA; Joseph Park, Lucio Ferreira, Pfizer Inc, Groton, CT; Ruth McKernan,
Pfizer Inc, Cambridge, United Kingdom; Larry D Altstiel, James W Kupiec, Pfizer Inc, Groton, CT; Natalie
Mount, Pfizer Inc, Cambridge, United Kingdom; Paul Maruff, CogState Inc, Melbourne, Australia
Abstract Body:
BACKGROUND: There are no approved therapies for reducing disability from stroke that are initiated beyond
the first few hours. Furthermore, in most studies where patients do receive an approved hyperacute stroke
therapy, most patients are left with significant disability despite overall efficacy. Therapies based on brain
repair have the potential to improve outcomes with a relatively wide time window. Preclinical studies of PF03049423 suggest efficacy for this approach with improvement in motor outcome when therapy is initiated up
to 3 days post stroke.
Moreover, clinical stroke trial designs have been criticized for their lack of concordance on key translational
endpoints demonstrated in animal stroke models. Thus, the design of the current clinical trial seeks to
specifically emulate the translational aspects of motor function consistently demonstrated in preclinical
neurorecovery stroke models.
OBJECTIVE: The objectives of this study are to evaluate the safety and tolerability of PF-03049423 following
multiple dose administration to subjects with ischemic stroke, including the relationship between PF-03049423
concentration and blood pressure. The study will also evaluate the efficacy of PF-03049423, relative to
placebo, in subjects with ischemic stroke following 90 days of therapy.
DESIGN: This is a multicenter, double-blind, placebo controlled, randomized, international study.
POPULATION STUDIED: A total of 240 stroke patients will be enrolled with dosing initiated 24-72 hours after
stroke onset.
Inclusion criteria NIHSS 6-20; the stroke must be radiologically confirmed by MRI to be ischemic and in the
territory of either the MCA, ACA, or PCA; age 18-85 years.
Exclusion criteria include severe acute or chronic medical or psychiatric condition apart from the index stroke,
women of child bearing potential, and uncontrolled hypertension.
Gender, introduction of thrombolytic therapy, and choice of antiplatelet therapy do not influence study eligibility.
INTERVENTION: Each patient will be randomized to receive placebo or PF-03049423 (1, 3, or 6 mg), p.o.
daily, for 90 days.
OUTCOME MEASURES: The primary outcome measure for Part 1 of the trial is safety and tolerability, as
determined from data, adverse events, vital signs, brain MRI, ECG, physical/neurological exam, NIHSS scores,
and laboratory tests over 14 days. In Part 2, the primary endpoint is the proportion of subjects with modified
Rankin Scale (mRS) score ≤2; over 90 days. Secondary outcome measures include plasma concentrations of
PF-03049423; Additionally, specific assessment of motor scores will provide a translational comparison from
the preclinical animal models to clinical, using Box & Blocks Test, Hand Grip Strength Test and gait velocity.
Additional endpoints include the proportion of subjects with day 90 mRS score ≤1, NIH Stroke Scale score ≤1,
Barthel Index (BI) ≥95 and BI=100. This trial will also assess scores on individual cognitive domains of interest
including RBANS Coding Sub Test, RBANS Naming Sub Test, Line Cancellation Test, and Recognition
Memory Test.
ANALYSIS: Adverse events and safety findings will be tabulated and examined. Estimates of the effect of PF03049423 at each dose relative to placebo will be calculated for behavioral/outcome measures. The proportion
of subjects with mRS ≤ 2 on Day 90 will be analyzed with a logistic regression including treatment, t-PA usage
for current stroke, geographical region as fixed effects and baseline NIHSS total score as a continuous
covariate.
TRIAL STATUS: Worldwide trial in 6 countries (~ 35 sites) with first enrollment expected in November, 2010.
Author Disclosure Block: M.M. Bednar: Employment; Modest; Significant. Employment; Significant;
Employee of Pfizer Inc. S.C. Cramer: Consultant/Advisory Board; Significant; Pfizer Inc. S.P. Finklestein: ;
Pfizer Inc. J. Park: Employment; Significant; Pfizer Inc. L. Ferreira: ; Pfizer Inc. R. McKernan: ; Pfizer Inc.
L.D. Altstiel: ; Pfizer Inc. J.W. Kupiec: ; Pfizer Inc. N. Mount: ; Pfizer Inc. P. Maruff: Other; Significant;
Contracted Organization.
Presentation Number: CT P38
PI Coordinator Affiliation: University of Nottingham, UK
PI Coordinator Name: Professor Philip Bath
Trial Abbreviation: PODCAST
Trial Contact Information: Mrs Lynn Stokes / [email protected] / Tel: +44 (0)115 8231671 / Fax:
+44 (0)115 8230273
Trial Email: [email protected]
Trial Name: Prevention Of Decline in Cognition After Stroke Trial
Trial Registry Number ID: ISRCTN85562386
Trial Sponsor: University of Nottingham, UK
Trial Web Site: www.podcast-trial.org/
Publishing Title: Podcast: Prevention Of Decline In Cognition After Stroke Trial: A Factorial Randomised Trial
Of Blood Pressure And Lipid Lowering
Author Block: Sandeep Ankolekar, Lynn Stokes, Philip M Bath, Univ of Nottingham, UK, Nottingham, United
Kingdom
Abstract Body:
Rationale: Stroke and dementia are common, economically costly to society, and devastating to patients and
their family. Elevated BP and cholesterol are common after stroke and may be associated with increasing
cognitive decline. Although BP-lowering post-stroke may reduce cognitive decline, there is little evidence to
date that lipid lowering is effective in preventing cognitive decline. Critically, it is unknown whether BP and
cholesterol should be lowered intensively, or moderately as per current guidelines. The aim of the proposed
trial is to determine if intensive BP and/or lipid lowering therapy after stroke is better in preventing cognitive
decline, compared to current guideline treatment.
Design: PODCAST is a prospective, randomised, open-label, blinded end-point, controlled, partial factorial,
phase IV trial. The start up phase will assess feasibility of the study over 3 years in 600 patients. The main
phase will then assess the efficacy of intensive treatment in a further 2,800 patients over 8 years in total. The
target SBP is <125 mm Hg for the intensive BP lowering group and <140 mm Hg for the guideline group. For
the intensive lipid lowering group the target LDL-C is <2 mmol/L and <3 mmol/L for the guideline group. The
primary outcome is Addenbrooke’s Cognitive Examination. Secondary outcomes include quality of life,
vascular events, functional outcome, depression and death.
Trial Status: The trial has Ethics and NHS R&D approvals and commenced recruitment in September 2010.
Author Disclosure Block: S. Ankolekar: None. L. Stokes: None. P.M.W. Bath: None.
Presentation Number: CT P39
PI Coordinator Affiliation: Stanford University Stroke Center
PI Coordinator Name: Gregory Albers
Trial Abbreviation: DIAS-4
Trial Contact Information: H. Lundbeck A/S
Trial Email: [email protected]
Trial Name: Desmoteplase In Acute Ischemic Stroke
Trial Registry Number ID: NCT00856661
Trial Sponsor: H. Lundbeck A/S, Copenhagen, Denmark
Trial Web Site: www.lundbeck-dias.com
Publishing Title: Desmoteplase in Acute Ischemic Stroke (DIAS) Clinical Trial Program: Regional Hub-Spoke
Recruitment in DIAS-4 in the United States
Author Block: Philip B Gorelick, Dept of Neurology, Univ of Illinois Coll of Med, Chicago, IL; Gregory W
Albers, Stanford Univ Stroke Ctr, Palo Alto, CA; Rüdiger von Kummer, Univ of Technology, Dresden, Germany
Abstract Body:
Introduction
The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program is designed to assess the safety and
efficacy of desmoteplase, a novel, highly fibrin-specific thrombolytic agent in Phase III of clinical development.
Currently, three studies are active: DIAS-3, DIAS-4, and DIAS-Japan. DIAS-3 and DIAS-4 were initiated in
2009 to evaluate the efficacy and safety of a single intravenous bolus of 90 µg/kg desmoteplase given 3-9
hours after onset of ischemic stroke (NIHSS Score 4-24, age 18-85 y). Patients (n=800) are selected with
occlusion or high-grade stenosis (TIMI scores 0-1) in proximal cerebral arteries as assessed by magnetic
resonance or computed tomography (CT) angiography. Recruitment in DIAS-3 is mainly focused on Asia and
Europe; while in DIAS-4 most sites are located in the United States.
DIAS-4 Hub-Spoke Model
The hub-spoke model is a well-known system that is successfully used in telemedicine-delivered stroke care.
In the DIAS-4 trial, it is implemented to support the recruitment and retention of acute ischemic stroke (AIS)
patients. Overall, the coordination of the system is done by the Central Coordinating Center (CCC) based at
the Center for Stroke Research at the University of Illinois College of Medicine, led by the first author of this
abstract. The CCC oversees six hubs in the United States: Midwest, Northeast, South/Southeast, Mid-Atlantic,
Southwest, and West. Each hub has a designated director, who is responsible for selection of and coordinating
their network of hospitals, patient recruitment and retention, and peer support for principal investigators. Each
of the six hubs will have 15-20 local sites, anticipating to recruit one to four patients per year per site. Sites are
selected based on willingness to commit to DIAS-4; competition for patients from current ongoing or
anticipated trials and from local interventionalists; availability of technology (e.g., CT angiography) and
personnel to begin study enrollment in a timely manner; adequate number of AIS patients; and track record of
success in the field. It is estimated that recruitment of 200 patients can be completed at US sites in 1.5-2
years. Recruitment is heightened by careful CCC surveillance and frequent communications via teleconference
or face-to-face meetings. Moreover, the CCC strives to maintain consistent messages to monitors, hub
directors, and local site staff. In addition, the CCC will review and discuss trial recruitment, patient/site
retention, and any other issues weekly with hub directors and H. Lundbeck, the sponsor of the DIAS program.
The hub-spoke model in the DIAS-4 trial will facilitate the progress of the DIAS program, which is important
because desmoteplase is the only thrombolytic agent in late-stage development despite the high unmet
treatment need in AIS. Many patients are not eligible for treatment because they fall outside the approved
therapeutic window (0-3 h): 50%-80% of patients arrive after 6 hours in many tertiary care centers. In addition,
US trials have largely excluded small- to medium-sized hospitals, where patients often arrive for initial
assessment.
Conclusion
The DIAS-4 trial initiative represents an academic-industrial collaboration of the type that is needed to move
the field of AIS treatment forward and to provide the US Food and Drug Administration, European Medicines
Agency, other regulatory agencies, and physicians with confidence in desmoteplase treatment outcomes. It
provides a network of both tertiary and community-based acute stroke centers representing standard clinical
practice for a majority of potential stroke patients. The initiative will provide an opportunity to extend medical
treatment to patients who would ordinarily not have access to thrombolytic therapy, and the results will be
important for physicians and patients in need of a safer, effective treatment for AIS.
Author Disclosure Block: P.B. Gorelick: Speakers; Modest; Boehringer Ingelheim. Honoraria; Modest;
Bayer, Takeda, Abbott, Roche/Parexel, Savient, H. Lundbeck A/S. Consultant/Advisory Board; Modest;
Boehringer Ingelheim. G.W. Albers: Honoraria; Modest; H. Lundbeck A/S, Boerhinger Ingelheim. R. von
Kummer: ; H. Lundbeck A/S.
Presentation Number: CT P40
PI Coordinator Affiliation: Reza Jahan
PI Coordinator Name: Jeffrey Saver
Trial Abbreviation: SWIFT Study
Trial Contact Information: ev3
Trial Email: None
Trial Name: Solitaire™ FR With The Intention For Thrombectomy (SWIFT) Study
Trial Registry Number ID: NCT01054560
Trial Sponsor: ev3
Trial Web Site: None
Publishing Title: Solitaire™ FR With The Intention For Thrombectomy (SWIFT) Study
Author Block: Jeffrey Saver, Reza Jahan, UCLA, Los Angeles, CA; Wayne Clark, Oregon Health & Science
Inst, Portland, OR; Elad Levy, Millard Fillmore Gates Circle Hosp, Buffalo, NY; Ronald Budzik, Riverside
Methodist Hosp, Columbus, OH; Tudor Jovin, Univ of Pittsburgh Medical Ctr, Pittsburgh, PA; Raul Nogueria,
Emory Univ, Atlanta, GA; Blaise Baxter, Erlanger Hosp, Chattanooga, TN; for the SWIFT Investigators
Abstract Body:
Background and Objective: The SOLITAIRE™ Revascularization Device is a retrievable stent designed to
restore blood flow in patients experiencing ischemic stroke due to large intracranial vessel occlusion. This trial
is intended to demonstrate substantial equivalence by obtaining prospective clinical data on the safety and
efficacy of the SOLITAIRE TM Device compared to MERCI® Device for patients diagnosed with acute ischemic
stroke.
Design: The SWIFT Study is a multi-center IDE, randomized, prospectively controlled study in clot retrieval for
patients diagnosed with an acute ischemic stroke. 200 patients will be enrolled in the study
Intervention: Patients who are ineligible for or who have failed IV t-PA are randomized to embolectomy
employing the Concentric Retriever or Solitaire FR within 8 hours of system onset.
Outcome Measures: The primary outcome is arterial recanalization of occluded target vessel measured by
TIMI score of 2 or 3 following the use of the SOLITAIRE™ or MERCI® Device without any symptomatic
intracranial hemorrhage. Secondary outcomes include time to initial recanalization, measurement of patient’s
neurological condition including NIHSS, Barthel Index and mRS at 30 and 90 days post procedure, rates of
morbidity and mortality, and incidence of intracranial hemorrhage
Analysis: The primary hypothesis is that the proportion of patients with TIMI flow of 2 or 3 will be non-inferior in
the SOLITAIRETM Device treated group compared to the control group, the MERCI® Device Study population,
using a clinically relevant non-inferiority margin Δ which is defined a priori to be 10%.
Trial Status: Actively recruiting. As of October 2010, 84 patients have been enrolled and 21 total sites are
participating.
Author Disclosure Block: J. Saver: Research Grant; Modest; ev3. Consultant/Advisory Board; Modest; ev3,
Concentric. R. Jahan: Consultant/Advisory Board; Significant; ev3. W. Clark: Research Grant; Significant;
ev3. E. Levy: ; ev3. Consultant/Advisory Board; Modest; ev3, Concentric. R. Budzik: Research Grant;
Significant; ev3. Consultant/Advisory Board; Modest; Concentric. T. Jovin: Research Grant; Significant; ev3.
Consultant/Advisory Board; Modest; ev3, Concentric. R. Nogueria: Research Grant; Modest; ev3.
Consultant/Advisory Board; Modest; ev3, Concentric. B. Baxter: Research Grant; Modest; ev3. Honoraria;
Significant; Concentric. Consultant/Advisory Board; Modest; ev3, Concentric.
Presentation Number: CT P41
PI Coordinator Affiliation: University of Southern California
PI Coordinator Name: Gene Sung
Trial Abbreviation: Advancing Telestroke Care
Trial Contact Information: Gene Sung, [email protected], 323.409.8686
Trial Email: [email protected]
Trial Name: Western States Stroke Consortium Telemedicne Project
Trial Registry Number ID: NCT012268862
Trial Sponsor: National Stroke Association
Trial Web Site: N/A
Publishing Title: Western States Stroke Consortium Telemedicine for Stroke Project
Author Block: Gene Y Sung, Univ of Southern California, Los Angeles, CA; Bart Demaerschalk, Mayo ClinicScottsdale, Phoenix, AZ; Chris Fanale, Swedish Medical Ctr, Denver, CO; Paul Katz, Renown Regional
Medical Ctr, Reno, NV; Jennifer Majersik, Univ of Utah, Salt Lake City, UT; David Tong, California Pacific
Medical Ctr, San Francisco, CA
Abstract Body:
On-Going Clinical Trial ABSTRACT
WSSC Teletroke Study
Western States Stroke Consortium Telemedicine for Stroke Study
NCT01226862
BACKGROUND
The use of telemedicine is rapidly expanding in the United States. It has been proven to be a useful tool in the
delivery of health care to rural and underserved areas. Although researchers estimate that up to 30% of stroke
patients could have improved outcomes based on use of iv-thrombolysis, actual rates of use remain
disappointingly low. This is especially true for stroke patients who live in more rural settings, where distances
to hospitals can be significant, and where there is typically no neurological presence to guide diagnosis and
treatment. Similar problems are encountered in some suburban “community” hospitals where bed-size (e.g. <
200 beds) is associated with the absence of 24/7 neurology support, a key requirement for guidelines-based
stroke care. Studies have reported accurate stroke diagnosis and increased use of tPA based on the use of a
variety of telemedicine solutions.
This study of telestroke across networks and systems boundaries is unique, previously published telestroke
studies have tended to focus on the results of a single network with common technological underpinnings. The
Advancing Telestroke Care study will establish treatment and outcomes in three distinct study cohorts: hub
telemedicine hospital, spoke telemedicine hospital and non-telemedicine control hospital.
OBJECTIVES
The objectives of the study are to:
· Determine if the use of telemedicine consultations for stroke patients will improve their care per guidelines
compared to stroke patients treated by control hospitals
· Determine if the care per guidelines provided via telemedicine consultations for stroke patients will be similar
or equivalent to care per guidelines provided to stroke patients treated at hub hospitals
DESIGN
This is a prospective observational study. 600 subjects meeting inclusion and exclusion criteria will be enrolled
consecutively over approximately 12 months and followed for 90 days post-stroke. The sites will be divided into
the following three cohorts:
· Hub hospital cohort: JCAHO-certified Primary Stroke Centers where patients are treated using hospital-based
stroke teams and pathways; these hospital personnel also provide telemedicine consultation to satellite
hospitals
· Spoke hospital cohort: non-stroke center certified sites, where patients are treated at an in-network telestroke
community hospital using telemedicine technology with consultation provided by physicians from a hub hospital
· Control hospital cohort: non-stroke center certified sites with no telemedicine services
·
The hub hospitals are five member hospitals of the Western States Stroke Consortium (WSSC): California
Pacific Medical Center, Mayo Clinic-Scottsdale, Renown Medical Center-Reno, Swedish Medical CenterDenver and the University of Utah. Each of the hub hospitals has affiliated spoke hospitals and has recruited
participating community hospitals as controls. The study will avoid selection bias by having many study sites,
which will include urban, suburban and rural hospitals.
To maintain patient demographic balance, enrollment of subjects will occur in blocks of 20 for each group at
each network. For instance, after 20 subjects are enrolled at a hub hospital, no more subjects can be enrolled
until there have also been 20 subjects enrolled at the affiliated spoke hospitals and 20 subjects enrolled at the
affiliated community hospitals.
Inclusion criteria:
Subjects will be eligible if the following criteria are met:
· Age ≥18 years old
· Acute stroke within 12 hours of symptom onset
Exclusion criteria:
Subjects who meet any of the following criteria will be excluded from this study:
· Life expectancy less than 90 days
· Patient unwilling to participate in study
The sample size provides sufficient power to detect differences in the primary endpoint across cohorts. The
statistical power and sample size were based on consecutive AIS patients in the 0 to 12 hour window resulting
in a high correct tPA decision rate at control hospitals since many patients were excluded from tPA due to
timing. Assuming correct tPA decision rates (as per tPA eligibility according to the ASA/AHA guidelines) of
88% in community hospitals with telestroke and 77% in community hospitals without telestroke, a sample size
was calculated to be 187 subjects per group (80% power) to detect an 11% telestroke effect size with 0.05 twosided significance level. In anticipation of a 6.5% attrition rate, a total of 600 subjects (200 in each group) will
be recruited to achieve a sample size goal of 187 subjects per group.
ASSESSMENTS AND OUTCOMES
•
Demographic data (age, race, gender)
•
Comorbidity data (heart disease, diabetes, cancer, concurrent medications)
•
Clinical evaluation (NIHSS, mRS, vital signs, radiologic and laboratory data)
Additional Assessment
Study investigators recognize the importance of being able to compare the costs of care across all study
cohorts. Each telestroke site will provide detailed descriptions of equipment and associated costs (including
operating and setup costs) of their respective telestroke networks. All sites will 1) describe the care provided:
what happens, how it happens, where it happens and 2) itemize cost elements such as tPA utilization (and
coding accuracy), hospital length of stay (LOS), and EMS road and air-ambulance transfer.
ANALYSIS
Data analysis will focus on the primary outcome measure, accurate decision making for IV tPA administration
in acute stroke as defined by ASA/AHA/ guidelines compared across cohorts.
Patient data will be analyzed within the study cohort their care originated. For example, if a patient entered
treatment through a spoke hospital and subsequently was transported to a hub hospital for further treatment,
patient data will be analyzed as part of the spoke hospital data. Investigators may conduct a secondary
analysis to examine the impact of assigning transported patients to receiving hospitals (and therefore, a
different study arm). This type of secondary analysis would only be considered for patients that were
transported in less than 24 hours after care was initiated. Patient data will also be analyzed between study
cohorts.
Detailed descriptions of equipment used in telestroke will be summarized and associated costs will be
tabulated. Such details will enable a directional view of the cost differences between stroke care provided via
hub/spoke hospitals and stroke care in control hospitals. Further, cost element detail will enable additional
health economic analyses in the future, should a formal cost effectiveness analysis be undertaken. Again,
formal health economic analysis of telestroke and telestroke networks of care is outside the scope of this
study.
Statistical analysis for the primary outcome will be performed using a random-effects logistic regression model
(PROC GLIMIXED in SAS). The accurate decision making of IV tPA administration will be modeled as a
function of the hospital cohort (spoke, control vs. hub hospital). The hospital cohort will be modeled as a fixed
effect, and the clinical site will be modeled as a random effect with an exchangeable correlation structure.
Potential confounding factors (e.g. time of symptom onset to treatment, NIHSS) will be included as covariates.
As we mentioned above in Section 4.4.4, patient data will be analyzed within the study cohort their care
originated. For example, if a patient entered treatment through a spoke hospital and subsequently was
transported to a hub hospital for further treatment, patient data will be analyzed as part of the spoke hospital
data. Patient data will also be analyzed between study cohorts. All analyses will be conducted using Statistical
Analysis System version 9.2 software (SAS Institute, Cary, NC). Statistical significance will be accepted at twosided p < 0.05.
Trial Status: Recruiting Patients
Author Disclosure Block: G.Y. Sung: None. B. Demaerschalk: None. C. Fanale: None. P. Katz: None. J.
Majersik: None. D. Tong: None.
Presentation Number: CT P42
PI Coordinator Affiliation: National University of Singapore, Singapore
PI Coordinator Name: Dr. Christopher Chen
Trial Abbreviation: CHIMES
Trial Contact Information: Chen, [email protected], +65 6516 5885
Trial Email: [email protected]
Trial Name: Double-Blind, Placebo Controlled, Randomized, Multicenter Study to Investigate CHInese
medicine NeuroAid Efficacy on Stroke Recovery
Trial Registry Number ID: NCT00554723
Trial Sponsor: National Medical Research Council of Singapore
Trial Web Site: http://chimes-society.org/
Publishing Title: The CHInese Medicine (MLC 601, NeuroAid®) Efficacy on Stroke recovery (CHIMES) Trial :
Progress and Safety Update.
Author Block: Christopher Chen, Chimes Society, Singapore, Singapore
Abstract Body:
Background and Aims : Stroke is a leading cause of death and disability worldwide. Despite improvements in
acute stroke treatment, many patients only make a partial or poor recovery. During the early days to weeks
following stroke, repair spontaneously occurs and the neurobiology of these events suggests a number of
therapeutic targets to further promote recovery. Traditional Chinese Medicine (TCM) is commonly used to
enhance the recovery process after stroke in China but lacks a reliable evidence base.
Methods : MLC 601, a TCM widely used in China to improve recovery after stroke, has recently been shown to
restore neurological and cellular function in animal models of stroke by processes involved in repair. Previous
clinical trials have shown that MLC601 shows good tolerability and superiority over another TCM in terms of
neurological disability and functional outcome. A large double blind randomized placebo controlled clinical trial
is underway to further assess the safety and efficacy of MLC 601.
Results : 665 patients (out of a planned total of 1100) have been randomised as of October 2010 from 16 sites
in 5 Asian countries. We assessed the safety of MLC 601 in a substudy of CHIMES. Longer term laboratory
safety data shows no differences between MLC601 and placebo, confirming MLC601’s safety in acute stroke
patients receiving a 3-month treatment.
Conclusions : Because TCM may be potentially beneficial with an encouraging safety profile, large
randomised, double blind, placebo controlled clinical trials using TCM focused on stroke rehabilitation and
repair, such as CHIMES are important.
Author Disclosure Block: C. Chen: Research Grant; Modest; funding support from the National Medical
Research Council of Singapore for CHIMES. Speakers; Modest; sponsorship from Moleac for travel to attend
the European Stroke Congress.
Presentation Number: CT P43
PI Coordinator Affiliation: University of Nottingham, United Kingdom
PI Coordinator Name: Professor Philip Bath
Trial Abbreviation: TARDIS
Trial Contact Information: Mrs Margaret Adrian/[email protected] /Tel: +44 (0)115 82
30210/Fax: +44 (0)115 82 30273
Trial Email: [email protected]
Trial Name: Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke
Trial Registry Number ID: ISRCTN47823388
Trial Sponsor: University of Nottingham, United Kingdom
Trial Web Site: www.tardistrial.org
Publishing Title: Triple Antiplatelets For Reducing Dependency After Ischaemic Stroke (tardis). Safety And
Tolerability Of Clopidogrel When Added To Aspirin And Dipyridamole In High Risk Patients With Recent
Ischaemic Stroke: A Randomised Controlled Trial
Author Block: Sandeep Ankolekar, Margaret J Adrian, Philip M Bath, Univ of Nottingham, Nottingham,
United Kingdom
Abstract Body:
Rationale: The risk of recurrence is greatest immediately after stroke or TIA. Existing prevention strategies
(antithrombotic, lipid/blood pressure lowering, endarterectomy) reduce, not abolish, further events. Dual
antiplatelet therapy - aspirin & clopidogrel (AC) for IHD, aspirin & dipyridamole (AD) for stroke, is superior to
aspirin monotherapy. We hypothesise that triple antiplatelet therapy (ACD) will be superior to AD in patients at
high-risk of recurrence, providing bleeding does not become excessive.
Design: TARDIS is a multicentre, parallel-group, prospective, randomised, open-label, blinded-endpoint,
controlled trial. In the start-up phase, we will assess over 3 years the safety, tolerability and feasibility of triple
therapy (ACD) versus dual therapy (AD) given for 1 month in 350 patients with acute stroke/TIA. The main
phase will then assess the safety and efficacy of ACD in up to 5000 patients. The primary outcome is ordinal
stroke (fatal/severe non-fatal/mild/TIA/none) at 90 days. Secondary outcomes include death, MI, vascular
events, function, bleeding, serious adverse events; sub-studies will assess cerebral emboli and platelet
function.
Trial Status: The trial started in April 2009. As of 02 November 2010, 249 patients have been recruited from 34
centres within the UK Stroke Research Network.
Author Disclosure Block: S. Ankolekar: None. M.J. Adrian: None. P.M.W. Bath: None.
Presentation Number: CT P44
PI Coordinator Affiliation: Univ of Wisconsin
PI Coordinator Name: Jon Matsumura
Trial Abbreviation: ACT I
Trial Contact Information: Sandy Lee, [email protected]
Trial Email: [email protected]
Trial Name: Asymptomatic Carotid Trial I
Trial Registry Number ID: NCT00106938
Trial Sponsor: Abbott Vascular
Trial Web Site: www.act1trial.com
Publishing Title: Asymptomatic Carotid Trial I
Author Block: Seemant Chaturvedi, WAYNE STATE UNIVERSITY, Detroit, MI; Lawrence Wechsler, Univ of
Pittsburgh, Pittsburgh, PA; Jon Matsumura, Univ of Wisconsin, Madison, WI; Kenneth Rosenfield,
Massachusetts General Hosp, Boston, MA; Gary Ansel, Riverside Hosp, Columbus, OH; Thomas Riles, NYU,
New York, NY
Asymptomatic Carotid Trial 1 (ACT 1)
NCT00106938
Objective:
To demonstrate non-inferiority of carotid artery stenting (CAS) using the Emboshield® Embolic Protection
System with the Xact® RX Carotid Stent System, when compared with carotid endarterectomy (CEA) for the
treatment of asymptomatic extra-cranial carotid stenotic disease.
Study Design
•
Prospective, randomized, parallel, 2-arm, multi-center trial
•
3:1 randomization ratio of CAS to CEA
•
Lead-in enrollment of up to 400 subjects
•
Maximum of 1658 pivotal subjects
•
Up to 100 sites in North America
•
Subjects followed at 1, 6, and 12 months post-procedure
and annually for 5 years
Eligible Patients
•
Asymptomatic
•
Standard risk for CEA
•
Single de novo lesion within the ICA, with or without
involvement of the common carotid artery
•
Stenosis ≥70% and ≤99% by angiography or
duplex ultrasound
Key Inclusion Criteria
•
Subject ≥18 and <80 years of age
•
Subject asymptomatic
No stroke or TIA (hemispheric or ocular)
within the 180 days prior to the procedure
Neurologist must confirm status
Key Exclusion Criteria
•
Symptomatic_stroke or TIA within 180 days
•
Bilateral carotid stenosis (contralateral stenosis
>60% by ultrasound or angiography)
•
High-risk surgical candidate
•
Known cardiac sources of emboli, including
paroxysmal or sustained atrial fibrillation
(treated or untreated)
•
Aortic arch anatomy unacceptable for carotid stent placement
•
Presence of carotid artery dissection, aneurysm, pseudo- aneurysm, arteritis, or fibromuscular dysplasia (FMD)
in
target vessel
•
Occlusion (TIMI 0 flow) or string sign of ipsilateral common
or internal carotid artery
•
Excessive calcification at lesion
•
Tortuosity* and/or occlusive disease that might preclude the safe introduction of a guiding catheter/sheath,
cerebral protection device, or stent
Primary Endpoint
•
Composite of Death, Stroke, MI at 30 days post procedure
PLUS
•
Ipsilateral Stroke from 31 to 365 days post procedure
Follow-up for endpoints
•
An independent CEC reviews and adjudicates the following events:
Cause of Death through 30 days (Attempt to determine if neurological, cardiac, other)
Suspected Stroke (All through 30 days, Ipsilateral between 31 days and 365 days (post-procedure)
Suspected MI (All suspected Q wave and non-Q wave through 30 days of procedure)
Study Progress
As of Sept 1, 2010:
Total Randomized Subjects: 1138
-
Total number of lead-ins to date: 189
Total number of sites initiated: 57
Lead in patient characteristics (n=180) as of 6/30/10:
Mean age 68.2 years
% male: 59%
Diabetes: 35.0%
HTN: 81.1%
Hyperlipidemia: 84.4%
CAD: 53.3%
Previous MI: 20.0%
Current smoker: 28.9%
Current contralateral disease: 50.6%
Previous coronary stent or angioplasty: 29.4%
Previous CABG: 23.3%
History of PAD: 28.9%
Lead in patient Outcomes (n=160) as of 6/30/10:
Death/stroke/MI 1.7%
All stroke 1.7%
Major stroke 0%
Minor stroke 1.7%
MI 0%
Conclusions
•
Level I evidence defines standards of clinical care
•
ACT I is a randomized trial comparing patients at standard risk for CEA and CAS
Only includes asymptomatic non-octogenarians patients
High levels of operator and interventional skills/experience
Routine embolic protection and dual antiplatelet therapy
•
All patients have modern medical therapy
•
Lead-in data suggests CAS event rates comparable to CEA
Author Disclosure Block: S. Chaturvedi: Consultant/Advisory Board; Significant; Abbott Vascular. L.
Wechsler: Consultant/Advisory Board; Significant; Abbott Vascular. J. Matsumura: Consultant/Advisory
Board; Significant; Abbott Vascular. K. Rosenfield: Consultant/Advisory Board; Significant; Abbott Vascular.
G. Ansel: Consultant/Advisory Board; Significant; Abbott Vascular. T. Riles: Consultant/Advisory Board;
Significant; Abbott Vascular.
Presentation Number: CT P45
PI Coordinator Affiliation: University of Massachusette Medical School
PI Coordinator Name: Susanne Muehlschlegel, M.D., M.P.H.
Trial Abbreviation: Safety Study of Dantrolene in Subarachnoid Hemorrhage
Trial Contact Information: Susanne Muehlschlegel, M.D., M.P.H.,
[email protected]
Trial Email: [email protected]
Trial Name: Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid
Hemorrhage – a Phase II Trial
Trial Registry Number ID: NCT01024972
Trial Sponsor: American Heart Association
Trial Web Site: n/a
Publishing Title: Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid
Hemorrhage - a Phase II Trial
Author Block: Susanne Muehlschlegel, Bridget Garland, Raphael Carandang, Wiley Hall, Univ of
Massachusetts Medical Sch, Worcester, MA; John R. Sims, Massachusetts General Hosp, Harvard Medical
Sch, Boston, MA
Abstract Body:
Rationale:
Subarachnoid hemorrhage (SAH) is one of the most devastating forms of stroke affecting primarily young
patients before the age of 65, and has a fatality of 50% in the first 30 days. For survivors of the initial insult,
cerebral vasospasm (CVSP) is the leading cause of disability and death, and therefore points to an inviting
therapeutic target. CVSP occurs in 70% of patients with SAH, and one third develops neurologic deficits.
Available treatments for CVSP are limited, and new treatments are needed.
Although CVSP is a multi-factorial disease process, the common pathway of vasoconstriction is the continuous
elevation of intracellular Ca2+-levels due to a combination of influx from extracellular Ca2+, and release from the
largest intracellular Ca2+ store, the endo/sarcoplasmatic reticulum mediated by the ryanodine receptor (RyR).
Nimodipine and nicardipine, both L-type specific Ca2+-channel blockers, have been used for CVSP, but are
only partially effective, possibly because they affect only the influx of extracellular Ca2+, and have no effect on
RyR-mediated intracellular Ca2+-release. Dantrolene is an F.D.A. approved RyR inhibitor. It is neuroprotective,
has been shown to inhibit cerebral vasoconstriction alone as well as in combination with nimodipine in an exvivo rat model, and two small human studies have suggested that dantrolene may attenuate CVSP after SAH.
Important potential side-effects that require study in a clinical trial in SAH patients include hyponatremia (its
chemical structure requires solution in free water and 5% mannitol), and liver toxicity (black box warning for
chronic dantrolene use).
Design:
Double-blind, placebo-controlled Phase II trial comparing intravenous dantrolene 1.25 mg IV every 6 hours x 7
days to placebo.
Eligibility:
Inclusion criteria are age ≥ 18 years, no upper age limit; documented aneurysmal SAH by CT/CT angiography
or cerebral angiography ≤ 5 days after aneurysmal SAH; this time window was chosen because it is highly
unlikely to have developed cerebral vasospasm before then; the aneurysm must have been secured either by
clipping or coiling; baseline serum sodium before enrollment ≥ 135 mmol/L. Exclusion criteria are patients with
severe clinical grade SAH (Hunt & Hess Grade 5 or World Federation of Neurological Surgeons Grade 5) due
to the high risk of developing brain edema and/or dying early from severity of SAH; radiological grade of
modified Fisher Scale of 1 or 0 due to the extremely low risk of developing cerebral vasospasm; patients
receiving mannitol, hypertonic saline or florinef prior to enrollment (both alter serum sodium); pregnant patients
(unknown risk of dantrolene to the unborn fetus). No restrictions to race will be made.
Recruitment Update:
A total n=30 (n=15 per group) will be recruited at a single center over a three year period. Currently, 15
patients have been enrolled (Sept 2009 - Oct 2010). Three patients did not complete the study: two patients
dropped out of the study by their own will (reasons: anxiety and nausea), one patient was given a dose of
23.4% saline by the clinical team for headache for suspicion of brain edema. One patient died several days
after the completion of the infusion period due to vessel rupture during cerebral angioplasty for vasospasm. An
interim analysis is in preparation (after half of all subjects have been recruited) and will be presented to the
data safety monitoring board.
Author Disclosure Block: S. Muehlschlegel: Research Grant; Significant; American Heart Association
Scientist Development Grant 09SDG2030022, Worcester Research Foundation Grant 2010. Other Research
Support; Significant; J.H.P. Pharmaceuticals (Parsippany, NJ) provides the study drug, but has no influence on
study design, execution or analysis.. B. Garland: None. R. Carandang: None. W. Hall: None. J.R. Sims:
None.
Presentation Number: CT P46
PI Coordinator Affiliation: Hospital das Clínicas/São Paulo University
PI Coordinator Name: Adriana B. Conforto
Trial Abbreviation: rTMS-Stroke
Trial Contact Information: Adriana Conforto, [email protected]
Trial Email: [email protected]
Trial Name: Low-frequency Transcranial Magnetic Stimulation To Enhance Motor Recovery In The Subacute
Phase After Stroke
Trial Registry Number ID: 2006/55504-0
Trial Sponsor: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Trial Web Site: None
Publishing Title: Low-frequency Transcranial Magnetic Stimulation To Enhance Motor Recovery In The
Subacute Phase After Stroke
Author Block: Adriana Conforto, Eduardo Mello, Erina Nagaya, Waldyr Santos Jr., Eduardo Melo, Milberto
Scaff, Hosp das Clinicas/Sao Paulo Univ, Sao Paulo, Brazil; Leonardo Cohen, Human Cortical Physiology
Section, NINDS, NIH, Bethesda, MD
Abstract Body:
Rationale: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere
(UH) transiently improves motor function in patients in the chronic phase after stroke. The goal of this study is
to investigate effects on motor recovery of low-frequency rTMS of the UH, administered in the subacute phase
after stroke.
Design: Randomized, double-blind clinical trial.
Intervention: Patients are randomized to either active or sham low-frequency rTMS of the UH followed by
physical therapy, five days a week, for two weeks.
Outcome measures:
Primary outcome: Motor function of the paretic hand evaluated with the Jebsen-Taylor test.
Secondary outcomes: Force of the paretic hand, Fugl-Meyer evaluation of motor performance (upper limb),
modified Rankin scale, Functional Independence Measure, NIH Stroke Scale, measures of corticomotor
excitability evaluated with transcranial magnetic stimulation.
Outcomes are evaluated at baseline, at end of treatment and one, three and six months after end of treatment.
Eligibility criteria:
Inclusion Criteria: First-ever ischemic stroke in the internal carotid artery territory confirmed by CT or MRI, 5-45
days before, leading to contralateral hand weakness; age, 18-80 years.
Exclusion criteria: cardiac pacemaker; pregnancy; implantable medication pump; intracranial hypertension;
history of seizures; metal in the head; decompressive surgery; other neurological diseases; shoulder pain; joint
deformity in the paretic upper limb; severe chronic disease such as end-stage cancer or end-stage renal
failure; inability to provide informed consent due to severe language or cognitive impairment.
Analysis: Intent to treat.
Status: Actively recruiting since February, 2008. As of October 25th, 2010, 27 patients have been enrolled.
Author Disclosure Block: A. Conforto: None. E. Mello: None. E. Nagaya: None. W. Santos: None. E.
Melo: None. M. Scaff: None. L. Cohen: None.
Presentation Number: CT P47
PI Coordinator Affiliation: Peking Union Medical College Hospital
PI Coordinator Name: LY Cui
Trial Abbreviation:
Trial Contact Information: [email protected]
Trial Email: [email protected]
TrialName:
Trial Registry Number ID: NCT00664846
TrialSponsor:
Trial Web Site: www.sps-pumch.com
Publishing Title: Interim Analysis of a Multi-center Trial in Secondary Ischemic Stroke Prevention in China
Author Block: Bin Peng, Yicheng Zhu, Jun Ni, Weihai Xu, Lixin Zhou, Ming Yao, Jianming Wang, Peking
Union Medical Coll Hospit, Beijing, China; Jiang Wu, Jilin Univ, Changchun, China; Chuanqiang Pu, 301 Hosp,
Beijing, China; Yongjun Wang, Beijing Tiantan Hosp, Beijing, China; Liying Cui, Peking Union Medical Coll
Hospit, Beijing, China; SMART Study Group
Abstract Body:
Background: Few information are available about the status of secondary ischemic stroke prevention in
China. We conducted a multicentre, paralleled, randomized, open label, controlled trial (SMART trial) to
evaluate the efficacy and safety of the standard medical management in secondary stroke prevention.
Methods: Patients were randomized to two groups: standard medical management group and usual care
group. In the interim analysis,we reviewed the baseline data of the two groups to evaluate the current status of
secondary ischemic stroke, no difference in intervention between two groups.
Results: At the time submission, 3904 patients were enrolled into the trial. Baseline characteristics of 3154
patients were available, 1504 patients in standard medical treatment group, 1631 patients in usual care group.
Among the 3154 patients, 68.26% were male, 26.07% have history of ischemic stroke, 7.18% of TIA, 2.26% of
intracerebral hemorrhage, 63.99% of hypertension, 22.55% of diabetes mellitus, 15.69% of dyslipidemia, 4.4%
of atrial fibrillation and 14.55% of coronary heart disease. Percentage of medicine usage for risk factor control
3 months before stroke onset were as following: 46.06% of antihypertension agents, 17.83% of antiplatelet,
16.67% of anticoagulant, 28.86% of lipid lowering agent, and 60.39% of antihyperglycemic agents.
Discussion: In China, hypertension is the first risk factor of ischemic stroke. Low use of medications for
control of risk factors indicates that patients are at high risk of ischemic stroke. Strategies of standard medical
intervention in secondary ischemic stroke are warranted.
Funding Supported by Key projects in the National Science & Technology Pillar Program in the Eleventh Fiveyear Plan Period
Contact Information:
PI (Corresponding author): LY Cui
Department of Neurology
Peking Union Medical College Hospital
Beijing, China PR 100730
Email: [email protected]
Website: www.sps-pumch.com
ClinicalTrial.gov Indentifier: NCT00664846
We have no conflict of interest.
Author Disclosure Block: B. Peng: None. Y. Zhu: None. J. Ni: None. W. Xu: None. L. Zhou: None. M.
Yao: None. J. Wang: None. J. Wu: None. C. Pu: None. Y. Wang: None. L. Cui: None.