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

NCT ID: NCT01043991

Last Updated: 2016-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-10-31

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.

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.

Conditions

Acute Myocardial Infarct

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

EPO

single bolus of EPO, 150 µg

Group Type: EXPERIMENTAL

Darbepoetin alfa

Intervention Type: DRUG

Placebo

NaCl

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Darbepoetin alfa

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

Exclusion Criteria

• Cardiogenic shock
• Cardiac arrest
• Currently receiving EPO
• Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe PIOT, Pr

Role: PRINCIPAL_INVESTIGATOR

Montpellier University Hospital

Locations

Montpellier University Hospital

Montpellier, , France

Countries

France

References

Roubille F, Micheau A, Combes S, Thibaut S, Souteyrand G, Cayla G, Bonello L, Lesavre N, Sportouch-Dukhan C, Klein F, Berboucha S, Cade S, Cung TT, Raczka F, Macia JC, Gervasoni R, Cransac F, Leclercq F, Barrere-Lemaire S, Paganelli F, Mottref P, Vernhet Kovacsik H, Ovize M, Piot C. Intracoronary administration of darbepoetin-alpha at onset of reperfusion in acute myocardial infarction: results of the randomized Intra-Co-EpoMI trial. Arch Cardiovasc Dis. 2013 Mar;106(3):135-45. doi: 10.1016/j.acvd.2012.12.001. Epub 2013 Feb 1.

Reference Type: DERIVED

PMID: 23582675 (View on PubMed)

Other Identifiers

8042

Identifier Type: -

Identifier Source: org_study_id