Design and rationale of the Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin after Large Myocardial Infarction (REVEAL) trial.

Abstract

BACKGROUND:

Acute myocardial infarction (MI) remains a leading cause of death despite advances in pharmacologic and percutaneous therapies. Animal models of ischemia/reperfusion have demonstrated that single-dose erythropoietin may reduce infarct size, decrease apoptosis, and increase neovascularization, possibly through mobilization of endothelial progenitor cells.

STUDY DESIGN:

REVEAL is a randomized, double-blind, placebo-controlled, multicenter trial evaluating the effects of epoetin α on infarct size and left ventricular remodeling in patients with large MIs. The trial comprises a dose-escalation safety phase and a single-dose efficacy phase using the highest acceptable epoetin α dose up to 60,000 IU. Up to 250 ST-segment elevation myocardial infarction patients undergoing primary or rescue percutaneous coronary intervention will be randomized to intravenous epoetin α or placebo within 4 hours of successful reperfusion. The primary study end point is infarct size expressed as a percentage of left ventricular mass, as measured by cardiac magnetic resonance imaging 2 to 6 days post study medication administration. Secondary end points will assess changes in endothelial progenitor cell numbers and changes in indices of ventricular remodeling.

CONCLUSION:

The REVEAL trial will evaluate the safety and efficacy of the highest tolerated single dose of epoetin α in patients who have undergone successful rescue or primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction.

• Authors: Chiara Melloni, Sunil V Rao, Thomas J Povsic, Laura Melton, Raymond J Kim, Rakhi Kilaru, Manesh R Patel, Mark Talan, Luigi Ferrucci, Dan L Longo, Edward G Lakatta, Samer S Najjar, Robert A Harrington
• Journal: American heart journal (Am Heart J) Vol. 160 Issue 5 Pg. 795-803.e2 (Nov 2010) ISSN: 1097-6744 [Electronic] United States
• PMID: 21095264 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2010 Mosby, Inc. All rights reserved.

Chemical References

• Hematinics
• Recombinant Proteins
• Erythropoietin
• Epoetin Alfa

Topics

• Aged
• Dose-Response Relationship, Drug
• Double-Blind Method
• Electrocardiography (drug effects)
• Epoetin Alfa
• Erythropoietin (administration & dosage)
• Follow-Up Studies
• Heart Ventricles (drug effects, pathology, physiopathology)
• Hematinics (administration & dosage)
• Humans
• Injections, Intravenous
• Magnetic Resonance Imaging, Cine
• Myocardial Infarction (diagnosis, drug therapy, physiopathology)
• Recombinant Proteins
• Recovery of Function (drug effects)
• Treatment Outcome
• United States
• Ventricular Function, Left (drug effects, physiology)
• Ventricular Remodeling (drug effects, physiology)