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.

Trial registration: ClinicalTrials.gov NCT00378352.

Copyright © 2010 Mosby, Inc. All rights reserved.

Figures

Figure 1. Study flow

Epoetin alfa doses of 15,000, 30,000, and 60,000 units are planned for evaluation in the dose-escalation safety phase. Initiation of increasing doses is contingent on review of safety data by the DSMB. The single-dose efficacy phase will involve the highest dose deemed acceptable by the DSMB.

Figure 2. CMR evaluation

(A) Outline of CMR techniques, timing, and physiological parameters. (B) Example of a cine-CMR and DE-CMR short-axis image with planimetry for LVEF, LV volumes, and infarct size. Areas of microvascular obstruction will also be noted (green arrow). (C) Primary, secondary, and tertiary CMR endpoints are listed.

Figure 3. Study schedule