REVEAL: Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction - Full Text View

Sponsor:	National Institute on Aging (NIA)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00378352

Purpose

The purpose of this study is to evaluate whether erythropoietin can help limit the damage to the heart in patients with acute heart attacks.

Condition	Intervention	Phase
Acute ST Elevation Myocardial Infarction	Drug: Erythropoietin (Epoetin alfa) Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effects of Erythropoietin on Infarct Size and Left Ventricular Remodeling in Survivors of Large Myocardial Infarctions

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack

Drug Information available for: Erythropoietin Epoetin alfa

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Changes in infarct size, as assessed by magnetic resonance imaging [ Time Frame: within 2-6 days of administration of study medication ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

End-systolic volume, end-diastolic volume, ejection fraction [ Time Frame: within 2-6 days of administration of study medication, and 3 months later ] [ Designated as safety issue: No ]
Number of circulating endothelial progenitor cells [ Time Frame: within 2-6 days of administration of study medication, and 3 months later ] [ Designated as safety issue: No ]
Changes in infarct size [ Time Frame: 3 months after administration of study medication ] [ Designated as safety issue: No ]
Changes in hemoglobin levels [ Time Frame: during the first two weeks following study medication administration ] [ Designated as safety issue: Yes ]
Occurrence of death or arterial or venous thrombotic events [ Time Frame: within 4 weeks following administration of study medication ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	210
Study Start Date:	September 2006
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 15,000 Units	Drug: Erythropoietin (Epoetin alfa) Single parenteral administration Other Name: Erythropoietin, Epoetin-Alpha, Procrit
Experimental: 2 30,000 Units	Drug: Erythropoietin (Epoetin alfa) Single parenteral administration Other Name: Erythropoietin, Epoetin-Alpha, Procrit
Experimental: 3 60,000 Units	Drug: Erythropoietin (Epoetin alfa) Single parenteral administration Other Name: Erythropoietin, Epoetin-Alpha, Procrit
Placebo Comparator: 4	Drug: Placebo single parenteral administration of saline placebo

Detailed Description:

REVEAL is a randomized, double-blinded, placebo-controlled, parallel phase II clinical study that will evaluate the effects of erythropoietin administration on infarct size, left ventricular remodeling and circulating endothelial progenitor cells in patients with large myocardial infarctions (MI). The study will be conducted in two phases: a dose-escalation safety phase and a single dose efficacy phase. Eligible patients who present to the hospital with an acute ST-elevation MI and who agree to participate in this study will be randomly assigned to receive a single infusion of study medication consisting either of erythropoietin or placebo. The size of the infarction and the dimensions of the heart will be assessed by cardiac magnetic resonance imaging (MRI) within 2-6 days of the infusion of the study medication, and again approximately 3 months later.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age > 21 years
Acute ST-elevation myocardial infarction
Referral for primary or rescue angioplasty
Revascularization procedure within 8 hours from the onset of ischemic symptoms
TIMI (Thrombolysis in myocardial infarction) flow grade 0 or 1 in the culprit coronary artery at the beginning of coronary angiography
Successful revascularization of infarct-related artery

Exclusion Criteria:

Clinical indication for erythropoietin
STEMI (ST-elevation myocardial infarction) due to occlusion of a branch vessel
Any history of prior MI, PCI (Percutaneous coronary intervention), CABG (Coronary artery bypass graft), cardiomyopathy, myocarditis, or CHF (congestive heart failure)
Hypersensitivity to human albumin, mammalian cell-derived products, or erythropoietin
Hematocrit > 42% in men or > 40% in women at the time of study drug administration
Uncontrolled hypertension at the time of study drug administration
Cardiogenic shock
Need for coronary surgical revascularization as determined at the time of the index coronary catheterization
History of hypercoagulable disorder, thromboembolic event, or venous thrombosis
History of stroke or TIA (transient ischemic attack)
History of seizures
Contraindication to MRI
Pregnancy or nursing mother

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378352

Locations

United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of Miami, School of Medicine
Miami, Florida, United States, 33136
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, Minnesota
Mayo Clinic-St. Mary's Hospital
Rochester, Minnesota, United States, 55902
United States, New York
New York Methodist Hospital
Brooklyn, New York, United States, 11215
Weill Medical College, Cornell University, NY Presbyterian Hospital
New York, New York, United States, 10021
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn State Heart & Vascular Institute
Hershey, Pennsylvania, United States, 17033
United States, Tennessee
Nashville Cardiovascular Magnetic Resonance Institute
Brentwood, Tennessee, United States, 37027
United States, Virginia
Virginia Commonwealth University Medical Center
Richmond, Virginia, United States, 23298

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Study Chair:	Edward Lakatta, MD	National Institute on Aging (NIA)
Principal Investigator:	Robert A. Harrington, MD,FACC,FSCAI	Duke University

More Information

Publications:

Maiese K, Li F, Chong ZZ. New avenues of exploration for erythropoietin. JAMA. 2005 Jan 5;293(1):90-5. Review.

Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res. 2004 Aug 1;63(2):208-16. Review.

Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest. 2003 Oct;112(7):999-1007.

Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta EG, Talan MI. Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11612-7. Epub 2003 Sep 19.

Moon C, Krawczyk M, Paik D, Lakatta EG, Talan MI. Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovasc Drugs Ther. 2005 Aug;19(4):243-50.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Najjar SS, Rao SV, Melloni C, Raman SV, Povsic TJ, Melton L, Barsness GW, Prather K, Heitner JF, Kilaru R, Gruberg L, Hasselblad V, Greenbaum AB, Patel M, Kim RJ, Talan M, Ferrucci L, Longo DL, Lakatta EG, Harrington RA; REVEAL Investigators. Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial. JAMA. 2011 May 11;305(18):1863-72.

Melloni C, Rao SV, Povsic TJ, Melton L, Kim RJ, Kilaru R, Patel MR, Talan M, Ferrucci L, Longo DL, Lakatta EG, Najjar SS, Harrington RA. Design and rationale of the Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin after Large Myocardial Infarction (REVEAL) trial. Am Heart J. 2010 Nov;160(5):795-803.e2.

Responsible Party:	Edward Lakatta, M.D., National Institute on Aging
ClinicalTrials.gov Identifier:	NCT00378352 History of Changes
Other Study ID Numbers:	AG0068, AG-260-05-10
Study First Received:	September 18, 2006
Last Updated:	October 15, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Ventricular Remodeling
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases

Cardiovascular Diseases
Vascular Diseases
Pathological Conditions, Anatomical
Epoetin Alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012