REVEAL: Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction

Acute ST Elevation Myocardial Infarction Clinical Trial

Official title:

Effects of Erythropoietin on Infarct Size and Left Ventricular Remodeling in Survivors of Large Myocardial Infarctions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00378352
• Other study ID #: 999905255
• Secondary ID: 05-AG-N255
• Status: Completed
• Phase: Phase 2
• First received: September 18, 2006
• Last updated: May 8, 2017
• Start date: September 2005
• Est. completion date: January 2011

Study information

• Verified date: May 2017
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: January 2011
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Acute ST Elevation Myocardial Infarction
• Infarction
• Myocardial Infarction
• Ventricular Remodeling

Intervention

Drug:
• Epoetin alfa
Randomized

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Nashville Cardiovascular Magnetic Resonance Institute	Brentwood	Tennessee
United States	New York Methodist Hospital	Brooklyn	New York
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Penn State Heart and Vascular Institute	Hershey	Pennsylvania
United States	University of Miami, School of Medicine	Miami	Florida
United States	Cornell University	New York	New York
United States	NY Presbyterian Hospital	New York	New York
United States	Weill Medical College	New York	New York
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Mayo Clinic, Rochester	Rochester	Minnesota
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Washington Hospital Center	Washington, D.C.	District of Columbia
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infarct Size in the Territory of the Infarct Related Artery	Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging.	performed 2 to 6 days after study medication administration (first CMR)
Secondary	Infarct Size in the Territory of the Infarct Related Artery	Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging.	12 ± 2 weeks after study medication
Secondary	LV Ejection Fraction		2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
Secondary	LV Volume Indexed to BSA		2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
Secondary	LV Mass Indexed to BSA		2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
Secondary	Vital Signs		baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
Secondary	Hemoglobin Levels		baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
Secondary	Reticulocyte Counts		baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
Secondary	Number of Participants With Clinical Events		from randomization to second CMR