Effects of Recombinant Human Erythropoietin on Platelet Function in Patients With Acute Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of this study is to see if a naturally-occurring hormone called erythropoietin changes the action of platelets in the blood. Patients with heart attacks are treated with medicines to reduce the clotting action of platelets. This study is trying to determine whether erythropoietin alters the clotting action of platelets in patients receiving anti-platelet medicines. It is important to understand the effects of erythropoietin on platelets since preliminary studies in animals suggest that erythropoietin may protect the heart from damage during a heart attack.

Detailed Description
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Anti-apoptotic effects of erythropoietin in experimental myocardial infarction (MI) and ischemia-reperfusion injury suggest potential for therapeutic benefit in patients with acute MI. Before the therapeutic potential of recombinant human erythropoietin (rHuEpo) in acute MI can be tested in large clinical trials, more information on the effects of short-term rHuEpo on platelet function are needed. Accordingly, the current proposal aims to determine the effects of rHuEpo (at a dose previously shown not to inhibit the anti-platelet effects of aspirin and clopidogrel in healthy subjects) on platelet function and other safety measures and measure of infarct size in patients with acute coronary syndromes receiving clinically-indicated standard anti-platelet therapy with aspirin, clopidogrel and glycoprotein Iib-IIIa inhibitors. Specific Aim 1: To determine the effects of intravenous rHuEpo 400 U/kg daily for 3 days vs. placebo on in vivo and in vitro platelet function in patients with acute MI undergoing percutaneous revascularization. Specific Aim 2: To obtain pilot data to estimate the effects of administration of rHuEpo 400 U/kg daily for 3 days vs. placebo on biochemical markers of myocardial infarction size and left ventricular ejection fraction in patients with acute MI undergoing percutaneous revascularization

Official Title
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Effects of Recombinant Human Erythropoietin on Platelet Function in Patients With Acute Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Recombinant human erythropoietin alfa (drug)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21-75 years Clinical evidence of acute myocardial infarction (MI) with total or sub-total occlusion on angiogram Status post percutaneous revascularization procedure for acute MI with TIMI 3 flow Ongoing clinically-indicated treatment with aspirin, thienopyridines Exclusion Criteria: Hemodynamic instability/shock or severe congestive heart failure Time from onset of chest pain to revascularization procedure > 16 hours Use of intravenous thrombolytic agents for treatment of MI Known need for additional revascularization procedures

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>recombinant human erythropoietin 200 U/kg IV daily for 3 days | Drug: Recombinant human erythropoietin alfa (drug)<br>* 200 U/kg IV daily for 3 days vs. matched volume of normal saline IV daily for 3 days<br>|
| Placebo Comparator: B<br>Normal saline volume to match active treatment IV daily for 3 days | Drug: Placebo<br>* Normal saline to match active drug (rHuEpo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Time | An integrated measure of in vivo platelet function and tissue hemostasis. | Change from Day 3 to Day 10 | 
| Platelet Function Assay Closure Time |  | Change from Day 3 to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction |  | Day 1 and Day 10 | 
| Serum Markers of Myocyte Damage | Myocyte Damage is represented by Creatine phosphokinase (CPK). CPK is measured in U/L, as scalar measure of the enzyme activity. CPK was measured for clinical indications laboratory. | Baseline | 
| Circulating Endothelial Progenitor Cells |  | Day 3 and Day 10 | 
| Serum Markers of Apoptosis | Apoptosis is represented by Fas ligand (FasL or CD95L). FasL (CD95L) is measured in pg/mL. | Day 1 and Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet function tests, Erythropoietin, Myocardial infarction