Clinical trial NCT00378352: REVEAL: Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction
Official title: Effects of Erythropoietin on Infarct Size and Left Ventricular Remodeling in Survivors of Large Myocardial Infarctions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute ST Elevation Myocardial Infarction
Keywords: Acute Myocardial Infarction
Left Ventricular Remodeling
Cardiac Magnetic Resonance Imaging
Endothelial Progenitor Cells
Infarct Size
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-09-20
Enrollment: 223
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 criteria: * INCLUSION CRITERIA:

Age greater than 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 greater than 42% in men or greater than 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

Primary outcomes:
measure: Infarct Size in the Territory of the Infarct Related Artery
timeFrame: performed 2 to 6 days after study medication administration (first CMR)
Secondary outcomes:
measure: Infarct Size in the Territory of the Infarct Related Artery
timeFrame: 12 ± 2 weeks after study medication
measure: LV Ejection Fraction
timeFrame: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
measure: LV Volume Indexed to BSA
timeFrame: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
measure: LV Mass Indexed to BSA
timeFrame: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
measure: Vital Signs
timeFrame: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
measure: Hemoglobin Levels
timeFrame: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
measure: Reticulocyte Counts
timeFrame: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
measure: Number of Participants With Clinical Events
timeFrame: from randomization to second CMR
Other outcomes:
Locations:
city: Washington, D.C.
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami, School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: New York
country: United States
facility: NY Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Weill Medical College
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Heart and Vascular Institute
state: Pennsylvania
city: Brentwood
country: United States
facility: Nashville Cardiovascular Magnetic Resonance Institute
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
Study officials:
affiliation: National Institute on Aging (NIA)
name: Edward G Lakatta, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/j.cardiores.2004.03.017.
citation: 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. doi: 10.1172/JCI18200.
citation: Maiese K, Li F, Chong ZZ. New avenues of exploration for erythropoietin. JAMA. 2005 Jan 5;293(1):90-5. doi: 10.1001/jama.293.1.90.
citation: Povsic TJ, Najjar SS, Prather K, Zhou J, Adams SD, Zavodni KL, Kelly F, Melton LG, Hasselblad V, Heitner JF, Raman SV, Barsness GW, Patel MR, Kim RJ, Lakatta EG, Harrington RA, Rao SV. EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy. J Thromb Thrombolysis. 2013 Nov;36(4):375-83. doi: 10.1007/s11239-013-0944-6.
citation: 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. doi: 10.1001/jama.2011.592.
citation: 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. doi: 10.1016/j.ahj.2010.09.007.