Acute Myocardial Infarct Clinical Trial
Official title:
Intracoronary Injection of Epo During Reperfusion in Patients Hospitalized for First Acute Myocardial Infarct STEMI
Primary endpoint: Is intracoronary injection of a single dose of darbepoetin alpha, during
reperfusion in patients hospitalized for ST segment elevation myocardial infarction (STEMI),
able to reduce infarct size ?
In in vivo studies, many experiments evidenced infarct size reduction, due to anti-apoptotic
compounds, when given during reperfusion, after cardiac ischemia. In humans,
post-conditioning offers such a protection, as the investigators have previously showed
(Staat P et al. Post-conditioning the human heart. Circulation. 2005 112(14):2143-8).
Infarct size reduction could lead to a reduced rate of complications (heart failure,
rhythmic complications) and finally, morbidity and even mortality. This protection depends
on anti-apoptotic properties (Zhao ZQ et al. Inhibition of myocardial injury by ischemic
postconditioning during reperfusion: comparison with ischemic preconditioning. Am J
Physiology Heart Circ Physiology 2003 Aug; 285(2):H579-88). Many drugs have been proposed to
be able to mimic this phenomenon. Among them, many are efficient but toxic in vivo or
difficult to manage (insulin, morphin). One of the most promising agent could then be
erythropoietin (EPO) (Opie LH et al. Postconditioning for protection of the infarcting
heart. Lancet. 2006; 367(9509):456-8). In order to target ischemia-reperfusion injuries, EPO
impact is better and better demonstrated (e.g.: Mudalagiri NR. Erythropoietin protects the
human myocardium against hypoxia and reoxygenation injury via phosphatidylinositol-3 kinase
and ERK1-2 activation. Br J Pharmacol. 2007 Oct 22). The purpose of the study is to test
this hypothesis in humans, on the onset of the reperfusion, after myocardial ischemia (acute
myocardial infarct). EPO could contribute to protect myocardium against ischemia-reperfusion
injury. This impact could rely on anti-apoptotic properties.
Multiple Centers.:
5 centers located in France:
- Montpellier
- Clermont-Ferrand
- Lyon
- Marseille
- Nîmes
Study design: Open-label, placebo-controlled, single-blinded. Patient in treatment group
will receive intracoronary single bolus of EPO (150 µg), as soon as significant reperfusion
is obtained (as measured by TIMI flow 2 or 3). In control group, placebo will be used.
Placebo must be presented exactly the same as the drug.
Length of Treatment: One shot during reperfusion procedure.
Follow-up Period: 72nd hour post-admission for plasma kinetics of cardiac enzymes 5th to 7th
day after revascularization procedure for MRI measurements, and echocardiography3th month
post-MI MRI, echocardiography3th month: phone contact.
Sample Size: 27 patients in each arm, 54 patients total.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment