Myocardial Infarction
Conditions
Keywords
Platelet function tests, Erythropoietin, Myocardial infarction
Brief summary
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
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
Interventions
200 U/kg IV daily for 3 days vs. matched volume of normal saline IV daily for 3 days
DRUGPlacebo
Normal saline to match active drug (rHuEpo)
Sponsors
American Heart Association
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Time | Change from Day 3 to Day 10 | An integrated measure of in vivo platelet function and tissue hemostasis. |
| Platelet Function Assay Closure Time | Change from Day 3 to Day 10 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction | Day 1 and Day 10 | — |
| Serum Markers of Myocyte Damage | Baseline | 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. |
| Circulating Endothelial Progenitor Cells | Day 3 and Day 10 | — |
| Serum Markers of Apoptosis | Day 1 and Day 10 | Apoptosis is represented by Fas ligand (FasL or CD95L). FasL (CD95L) is measured in pg/mL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rHuEPO recombinant human erythropoietin 200 U/kg IV daily for 3 days | 29 |
| Placebo Normal saline volume to match active treatment IV daily for 3 days | 15 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | rHuEPO | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 7 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 22 Participants | 35 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 9 | 58 years STANDARD_DEVIATION 12 | 56 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 15 participants | 29 participants | 44 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 15 |
| other Total, other adverse events | 0 / 29 | 0 / 15 |
| serious Total, serious adverse events | 1 / 29 | 1 / 15 |
Outcome results
Primary
Bleeding Time
An integrated measure of in vivo platelet function and tissue hemostasis.
Time frame: Change from Day 3 to Day 10
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Bleeding Time | 1020 seconds |
| rHuEPO | Bleeding Time | 1020 seconds |
Primary
Platelet Function Assay Closure Time
Time frame: Change from Day 3 to Day 10
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Platelet Function Assay Closure Time | 251 seconds |
| rHuEPO | Platelet Function Assay Closure Time | 281 seconds |
Secondary
Circulating Endothelial Progenitor Cells
Time frame: Day 3 and Day 10
Population: Endothelial progenitor cells could not be isolated and are therefore not reported.
Secondary
Left Ventricular Ejection Fraction
Time frame: Day 1 and Day 10
Population: These data were not collected due to lack of funds.
Secondary
Serum Markers of Apoptosis
Apoptosis is represented by Fas ligand (FasL or CD95L). FasL (CD95L) is measured in pg/mL.
Time frame: Day 1 and Day 10
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Markers of Apoptosis | Day 1 | 45 pg/mL | Standard Deviation 12 |
| Placebo | Serum Markers of Apoptosis | Day 10 | 60 pg/mL | Standard Deviation 18 |
| rHuEPO | Serum Markers of Apoptosis | Day 1 | 56 pg/mL | Standard Deviation 19 |
| rHuEPO | Serum Markers of Apoptosis | Day 10 | 63 pg/mL | Standard Deviation 22 |
Secondary
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.
Time frame: Baseline
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Serum Markers of Myocyte Damage | 817 U/L |
| rHuEPO | Serum Markers of Myocyte Damage | 652 U/L |