Download stem-ami outcome trial

STEM-AMI OUTCOME TRIAL
STem cElls Mobilization
in Acute Myocardial Infarction Outcome Trial
A national, multicentre, randomised, open-label, Phase III study
Dott. Luca Deferrari
U.O. Cardiologia
IRCCS San Martino, Genova
What is G-CSF?
• Granulocyte Colony Stimulating Factor
– Glycoprotein
– Growth factor
– Cytokine
• Produced by endothelium, macrophages and
other immune cells
• G-CSF receptor present on precursor cells in the
bone marrow
– Initiates proliferation and differentiation into mature
granulocytes
– Stimulates bone marrow cell release into circulation
Two important G-CSF uses
1.
MOST COMMON: Post chemotherapy febrile
neutropenia
2.
Potent inducer of hematopoietic stem cell
mobilization for stem cell transplantation
Side effects associated with G-CSF
STEM–AMI Outcome trial: rationale
STEM–AMI Outcome trial: rationale
STEM–AMI Outcome trial: rationale
STEM –AMI Outcome trial: rationale
STEM–AMI Outcome trial: rationale
STEM–AMI Outcome trial: rationale
STEM–AMI Outcome trial: rationale
STEM-AMI OUTCOME TRIAL
STUDY OBJECTIVES
To demonstrate that G-CSF in addition to state of the art
treatment is safe and significantly improves clinical
outcome in patients with reduced left ventricular EF
(≤45%) after successful reperfusion for large anterior
acute myocardial infarction
STEM-AMI OUTCOME TRIAL
DESIGN
Phase III, randomized, open label.
1530 Patients (50 centres) will be randomized to standard
therapy + G-CSF or standard therapy alone in 1:1 ratio.
Accrual time 3 years. Follow-up time 2 years.
TREATMENT
FILGRASTIM 5 µg/kg will be administered subcutaneously
bis in die for 6 days (from Day 1 to Day 6), starting within
24 h after PCI and reperfusion.
STEM-AMI OUTCOME TRIAL
PRIMARY EFFICACY END POINT
Clinical outcome will be assessed by the composite endpoint of:
• death or
• recurrence of MI or
• hospitalization due to heart failure
SAFETY ENDPOINTS
• Incidence and severity of bleeding complications
• Incidence of malignancy
• Incidence and intensity of AEs and SAEs
STEM-AMI OUTCOME TRIAL
INCLUSION CRITERIA
• Patients affected by acute anterior STEMI undergoing primary PCI
(or PCI-rescue with persistent occlusion of coronary artery)
• Time symptom-to-balloon ≥3 h and ≤12h (or ≤24 h if symptoms
persist)
• TIMI flow post PCI ≥2
• Evidence of LV dysfunction (EF biplane ≤ 45%) ≤ 24 h after
revascularization
• Men and women aged ≥18 years and ≤ 75 years,
• Informed consent must be signed before proceeding with any study
procedure.
STEM-AMI OUTCOME TRIAL
EXCLUSION CRITERIA
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Previous anterior MI
Recent MI (within 1 month)
ANAMNESI EXTRACARDIACA
Known previous LV dysfunction (EF <45%),
ANAMNESI
Angiographic evidence of coronary
anatomy notCARDIOLOGICA
suitable for PCI
mieloproliferative,
leucemia
Valve disease •Malattie
requiring surgical
correction
EMOCROMO
•Pregresso
IMA anteriore
History of previous cardiac surgery or PCI on LAD within 6 months
•Neoplasie
Previous or current•IMA
documented
history
of leukemia, myeloproliferative or myelodisplastic
nel mese
precedente
•
Hb
<10
g/dl
disorder, malignant
•HIVdisease
Haemoglobin <10 •Nota
mg/dl disfunzione VSx (FE ≤ 45% )
•Patologia
autoimmune
White blood cells
>25.000
mm3 >25.000/mm3
• (WBC)
Globuli
bianchi
•Valvulopatia
con indicazione CCH
Platelet <50.000 mm3
•Interstiziopatia polmonare
Sepsis
•Pregressa CCH nei 6 mesi
3 precedenti
•
Piastrine
<50.000/mm
Known HIV infection
•Gravidanza o allattamento
•Pregressa PCI su IVA nei 6 mesi precedenti
Immune system diseases
•Abuso di alcool e/o droghe
Interstitial lung disease
Serious concomitant
medical
conditions (other than ischemic heart disease)
•Scarsa
compliance
Pregnancy and breast feeding
Documented alcohol and drug abuse
Anticipated poor compliance
Current participation in a clinical trial with other investigational products or cell therapy
STEM-AMI OUTCOME TRIAL
Assessment
I
Assessment
II
Assessment
III
Assessment
IV
Assessment
V
Assessment
VI
Day -1/0
In hospital
phase
1 month
6 months
12 months
24 months
STEM-AMI OUTCOME TRIAL
ASSESMENT I DAY -1/0
Screening and randomization
•
•
•
•
•
•
•
•
•
Obtain written informed consent
Documented acute anterior STEMI
Documented primary PCI/PCI-rescue (symptom to ballon time)
TIMI flow post-PCI registration
Evidence of Echo Simpson biplane EF ≤45%, EDV and ESV
Hemochrome (hemoglobin, platelets, WBC)
Pregnancy test (if necessary)
Determine patient’s eligibility for enrollment
Randomization to study treatment group
STEM-AMI OUTCOME TRIAL
ASSESMENT II DAY 0-7
In Hospital phase
• G-CSF administration
• Hemochrome (WBC count)
• Documentation of ADRs/SAEs
• ECG
• ECHO: EF (Echo Simpson biplane), EDV and ESV
STEM-AMI OUTCOME TRIAL
ASSESMENT III DAY 30
1-month visit
• Clinical Evaluation
• Documentation of ADRs/SAEs
• ECG
STEM-AMI OUTCOME TRIAL
ASSESMENT IV DAY 180
6-months visit
• Clinical Evaluation
• Documentation of ADRs/SAEs
• ECG
• ECHO: EF (Echo Simpson biplane), EDV and ESV
STEM-AMI OUTCOME TRIAL
ASSESMENT V DAY 365
12-months visit
• Phone interview
• Documentation of ADRs/SAEs
STEM-AMI OUTCOME TRIAL
ASSESMENT V DAY 730
24-months visit
• Clinical Evaluation
• Documentation of ADRs/SAEs
• ECG
• ECHO: EF (Echo Simpson biplane), EDV and ESV
STEM-AMI OUTCOME TRIAL
Egregi Dottori,
Con la presente, comunichiamo che oggi, 8 novembre 2013, è stato
arruolato il primo paziente dello Studio STEM-AMI Outcome
dall'Ospedale San Gerardo di Monza.
Cordialmente
Segreteria Organizzativa
Centro di Coordinamento Centro Studi ANMCO
Grazie per l’attenzione