Intracoronary Injection of Epo After Myocardial Infarct "Intra-CO-EpoMI"

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Completed

CT.gov ID

NCT01043991

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myocardial Infarct	Drug: Darbepoetin alfa Drug: Placebo	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Intracoronary Injection of Epo During Reperfusion in Patients Hospitalized for First Acute Myocardial Infarct STEMI

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Jul 1, 2010

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EPO single bolus of EPO, 150 µg	Drug: Darbepoetin alfa
Placebo Comparator: Placebo NaCl	Drug: Placebo

Arm

Intervention/Treatment

Experimental: EPO

single bolus of EPO, 150 µg

Drug: Darbepoetin alfa

Placebo Comparator: Placebo

NaCl

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Magnetic resonance imaging (MRI) determination of infarct size [12 weeks]

Secondary Outcome Measures

Cardiac enzymes [12 weeks]
Echocardiography [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ACS with persistent ST elevation
First episode
Symptoms onset < 12 hours
Eligible for angioplasty
Culprit coronary artery occluded (TIMI flow 0-1) at admission, and then adequately reperfused (TIMI flow 2-3) prior to EPO injection