Intracoronary Injection of Epo After Myocardial Infarct "Intra-CO-EpoMI"
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Intracoronary Injection of Epo During Reperfusion in Patients Hospitalized for First Acute Myocardial Infarct STEMI|
- Magnetic resonance imaging (MRI) determination of infarct size [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Cardiac enzymes [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Echocardiography [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Study Completion Date:||October 2011|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
single bolus of EPO, 150 µg
|Drug: Darbepoetin alfa|
Placebo Comparator: Placebo
5 centers located in France:
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01043991
|Montpellier University Hospital|
|Montpellier, France, 34000|
|Principal Investigator:||Christophe PIOT, Pr||Montpellier University Hospital|