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

Study Overview
=================
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.

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

Conditions
-----------------
Acute ST Elevation Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Epoetin alfa


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Dose Escalation Safety<br>The objective of the first phase is to evaluate the safety of escalating doses of Epoetin alfa in patients with STEMIs. | Drug: Epoetin alfa<br>* Randomized<br>* Other names: PROCRIT;|
| Placebo Comparator: Single Dose Efficacy<br>Single parenteral administration of 60000 U of epoetin alfa. The objectives of the second phase are to investigate the effects of the highest safe dose on infarct size, left ventricular remodeling and endothelial progenitor cells. | Drug: Epoetin alfa<br>* Randomized<br>* Other names: PROCRIT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| LV Ejection Fraction |  | 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR) | 
| LV Volume Indexed to BSA |  | 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR) | 
| LV Mass Indexed to BSA |  | 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR) | 
| Vital Signs |  | baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days | 
| Hemoglobin Levels |  | baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days | 
| Reticulocyte Counts |  | baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days | 
| Number of Participants With Clinical Events |  | from randomization to second CMR | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Myocardial Infarction, Left Ventricular Remodeling, Cardiac Magnetic Resonance Imaging, Endothelial Progenitor Cells, Infarct Size