Download MR RESCUE

MR RESCUE: Mechanical Retrieval and Recanalization of
Stroke Clots Using Embolectomy 3.1b
Objectives
1. To test the hypothesis that the presence of substantial ischemic penumbral tissue
visualized on multimodal imaging (MRI or CT) predicts patients most likely to
respond to mechanical embolectomy for treatment of acute ischemic stroke due
to a large vessel occlusion up to 8 hours from symptom onset.
This hypothesis will be tested by analyzing whether pretreatment imaging
pattern has a significant interaction with treatment as a determinant of functional
outcome. The primary study endpoint employed to test this hypothesis will be
the distribution of scores on the modified Rankin Scale measure of global
handicap assessed 90 days post-stroke.
2. To test the nested hypothesis that patients with a penumbral imaging pattern
have improved functional outcome when treated with mechanical embolectomy
vs. standard medical care.
The primary study endpoint employed to test this hypothesis in a treatment
superiority analysis will be the distribution of scores on the modified Rankin
Scale measure of global handicap assessed 90 days post-stroke between the
embolectomy and control groups among patients with a penumbral imaging
pattern at entry.
3. To test the nested hypothesis that patients without a penumbral imaging pattern
do not have improved functional outcomes when treated with mechanical
embolectomy vs. standard medical management, and to determine in an
exploratory manner if there is a signal of potential moderate efficacy or harm.
The primary study endpoint employed to test this hypothesis in a treatment
equivalency analysis will be the distribution of scores on the modified Rankin
Scale measure of global handicap assessed 90 days post-stroke between the
embolectomy and control groups among patients with a non-penumbral imaging
pattern at entry.
4. To test the hypothesis that patients treated with mechanical embolectomy have
improved functional outcome vs. standard medical management (to be tested if
the primary hypothesis of interaction is negative). The endpoint employed to test
this hypothesis in a treatment superiority analysis will be the distribution of
scores on the modified Rankin Scale measure of global handicap assessed 90
days post-stroke between the embolectomy and control groups among patients.
Study Design
Adult male or female patients, presenting within 8 hours of symptoms onset and
meeting inclusion criteria at each of the study sites will be assessed for possible
enrollment into the study.
Patients will be screened for eligibility by a study investigator as soon as possible after
arrival to the hospital or, for patients who have a stroke in the hospital, as soon as
possible after onset of symptoms. The screening process will involve the following:
 Medical history and physical examination
 Premorbid mRS and BI
 Scoring of neurologic deficit, using the NIHSS
 Pretreatment multimodal MRI or multimodal CT confirming acute cerebral
ischemia with a large vessel occlusion on MR or CT angiography
 Laboratory tests (hemoglobin, hematocrit, white blood cell count, platelet count,
INR, activated partial thromboplastin time, prothrombin time, serum creatinine,
blood glucose, pregnancy test for women of childbearing age and EKG)
Once inclusion/exclusion criteria are satisfied, the imaging data will be transferred to
the dedicated MR RESCUE computer for image post-processing. The computer
program will automatically generate a 4 digit randomization code. The investigator
must call the MR RESCUE on-call physician prior to study enrollment – the name and
contact number of the MR RESCUE on call physician can be located on the MR RESCUE
website: http://mrrescue.ucla.edu. The patient will then be enrolled employing explicit
consent procedures. The consent provider will be the patient if he or she is competent or
the patient's legally authorized representative if the patient is not competent. Once
informed consent has been obtained, the study investigator enters the patient’s data into
the dedicated MR RESCUE website: http://mrrescue.ucla.edu. The investigator must
also enter the code for penumbral pattern. Based on this information, the website will
generate a randomization number and treatment assignment for the patient.
Treatment
If randomized to embolectomy therapy, the patient will be immediately transported to
the neurointerventional angiographic suite following the MRI or CT for mechanical
embolectomy
Patients randomized to the control group will receive best conventional medical
therapy for acute ischemic stroke as determined by the attending stroke physician.
Number of Subjects: Total up to 120 subjects will be enrolled.
Inclusion/Exclusion Criteria
Inclusion Criteria:
1. New focal disabling neurologic deficit consistent with acute cerebral ischemia
(NIHSS  6 with at least six points attributed to current stroke)
2. Age  18 ≤ 85
3. Clot retrieval procedure can be initiated within 8 hours from onset
4. Large vessel proximal anterior circulation occlusion on MR or CT angiography
(internal carotid, M1 or M2 MCA)
5. Signed informed consent obtained from the patient or patient’s legally
authorized representative
6. Pretreatment multimodal MRI or CT performed according to MR RESCUE
protocol
7. Premorbid modified Rankin score of 0-2
8. Allowed but not required: patients treated with IV tPA up to 4.5 hours from
symptom onset with persistent target occlusion on post-treatment MR RESCUE
MR or CT protocol performed at the completion of drug infusion (Note: Rapidly
improving neurological signs prior to randomization is an exclusion).
Exclusion Criteria:
NIHSS  30
Acute intracranial hemorrhage
Coma
Rapidly improving neurological signs prior to randomization
Pre-existing medical, neurological or psychiatric disease that would confound
the neurological, functional, or imaging evaluations
6. Pregnancy
7. Known allergy to iodine previously refractory to pretreatment medications
8. Current participation in another experimental treatment protocol
9. Contrast-Enhanced Neck MRA or CTA suggests proximal ICA occlusion,
proximal carotid stenosis > 67%, or dissection
10. INR > 3.0
11. PTT > 3 x Normal
12. Imaging data cannot be processed by MR RESCUE computer
13. Renal failure: serum creatinine > 2.0 or GFR < 30
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MRI Exclusion Criteria:
Contraindication to MRI (pacemaker etc)
CT Exclusion Criteria
Contraindication to iodinated contrast**
**Examples of possible iodinated contrast contraindications include:
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Hyperthyroidism
History of severe allergic reaction to iodinated contrast material
History of severe kidney disease as an adult, including tumor or transplant
surgery, or family history of kidney failure
Paraproteinemia syndromes or multiple myeloma
Collagen vascular disease
Severe cardiac insufficiency
Severely compromised liver function
Current therapy with metformin, aminoglycosides