Acute ST Elevation Myocardial Infarction
Conditions
Keywords
Acute Myocardial Infarction, Left Ventricular Remodeling, Cardiac Magnetic Resonance Imaging, Endothelial Progenitor Cells, Infarct Size
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.
Interventions
DRUGEpoetin alfa
Randomized
Sponsors
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infarct Size in the Territory of the Infarct Related Artery | performed 2 to 6 days after study medication administration (first CMR) | Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Infarct Size in the Territory of the Infarct Related Artery | 12 ± 2 weeks after study medication | Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging. |
| 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 | — |
| Vital Signs | baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days | — |
Countries
United States
Participant flow
Recruitment details
Conducted at 28 US sites between October 2006 and February 2010 and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy
Participants by arm
| Arm | Count |
|---|---|
| Epoetin Alfa Dose escalation and efficacy phases | 123 |
| Placebo Dose escalation and efficacy phases | 99 |
| Total | 222 |
Baseline characteristics
| Characteristic | Epoetin Alfa | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 12.4 | 55.6 years STANDARD_DEVIATION 12.5 | 56 years STANDARD_DEVIATION 12 |
| Age, Customized Greater than or equal to 70 years | 20 Participants | 18 Participants | 38 Participants |
| Age, Customized Less than 70 years | 103 Participants | 81 Participants | 184 Participants |
| Region of Enrollment United States | 123 participants | 99 participants | 222 participants |
| Sex: Female, Male Female | 23 Participants | 21 Participants | 44 Participants |
| Sex: Female, Male Male | 100 Participants | 78 Participants | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 125 | 36 / 97 |
| serious Total, serious adverse events | 25 / 125 | 10 / 97 |
Outcome results
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.
Time frame: performed 2 to 6 days after study medication administration (first CMR)
Population: Analysis only performed on subjects who completed the CMR examination
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa | Infarct Size in the Territory of the Infarct Related Artery | 15.8 percentage of LV mass | Standard Deviation 10.3 |
| Placebo | Infarct Size in the Territory of the Infarct Related Artery | 15.0 percentage of LV mass | Standard Deviation 10 |
Secondary
Hemoglobin Levels
Time frame: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoetin Alfa | Hemoglobin Levels | Baseline | 13.8 g/dL | Standard Deviation 1.4 |
| Epoetin Alfa | Hemoglobin Levels | 14 days | 14.1 g/dL | Standard Deviation 1.4 |
| Epoetin Alfa | Hemoglobin Levels | 48 hours | 13.3 g/dL | Standard Deviation 1.7 |
| Epoetin Alfa | Hemoglobin Levels | 30 days | 14.2 g/dL | Standard Deviation 1.4 |
| Epoetin Alfa | Hemoglobin Levels | 24 hours | 13.4 g/dL | Standard Deviation 1.5 |
| Placebo | Hemoglobin Levels | 30 days | 13.7 g/dL | Standard Deviation 1.5 |
| Placebo | Hemoglobin Levels | 24 hours | 13.1 g/dL | Standard Deviation 1.7 |
| Placebo | Hemoglobin Levels | Baseline | 13.6 g/dL | Standard Deviation 1.7 |
| Placebo | Hemoglobin Levels | 48 hours | 13.1 g/dL | Standard Deviation 1.8 |
| Placebo | Hemoglobin Levels | 14 days | 13.5 g/dL | Standard Deviation 1.5 |
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.
Time frame: 12 ± 2 weeks after study medication
Population: Analysis only performed on subjects who completed the CMR examination
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa | Infarct Size in the Territory of the Infarct Related Artery | 10.6 percentage of LV mass | Standard Deviation 8.6 |
| Placebo | Infarct Size in the Territory of the Infarct Related Artery | 10.4 percentage of LV mass | Standard Deviation 7.6 |
Secondary
LV Ejection Fraction
Time frame: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
Population: Analysis only performed on subjects who completed this component of the CMR examination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoetin Alfa | LV Ejection Fraction | First CMR | 48.2 percent | Standard Deviation 9.1 |
| Epoetin Alfa | LV Ejection Fraction | Second CMR | 52.5 percent | Standard Deviation 9.3 |
| Placebo | LV Ejection Fraction | First CMR | 48.9 percent | Standard Deviation 8.7 |
| Placebo | LV Ejection Fraction | Second CMR | 52.0 percent | Standard Deviation 8.8 |
Secondary
LV Mass Indexed to BSA
Time frame: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
Population: Analysis only performed on subjects who completed this component of the CMR examination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoetin Alfa | LV Mass Indexed to BSA | First CMR | 74.2 g/m^2 | Standard Deviation 15.2 |
| Epoetin Alfa | LV Mass Indexed to BSA | Second CMR | 67.3 g/m^2 | Standard Deviation 14.7 |
| Placebo | LV Mass Indexed to BSA | First CMR | 69.2 g/m^2 | Standard Deviation 13 |
| Placebo | LV Mass Indexed to BSA | Second CMR | 61.8 g/m^2 | Standard Deviation 14.1 |
Secondary
LV Volume Indexed to BSA
Time frame: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)
Population: Analysis only performed on subjects who completed this component of the CMR examination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoetin Alfa | LV Volume Indexed to BSA | End systolic, First CMR | 34.7 ml/m^2 | Standard Deviation 14.7 |
| Epoetin Alfa | LV Volume Indexed to BSA | End systolic, Second CMR | 34.1 ml/m^2 | Standard Deviation 14 |
| Epoetin Alfa | LV Volume Indexed to BSA | End diastolic, First CMR | 65.6 ml/m^2 | Standard Deviation 18.2 |
| Epoetin Alfa | LV Volume Indexed to BSA | End diastolic, Second CMR | 70.0 ml/m^2 | Standard Deviation 17.1 |
| Placebo | LV Volume Indexed to BSA | End diastolic, Second CMR | 66.6 ml/m^2 | Standard Deviation 19.1 |
| Placebo | LV Volume Indexed to BSA | End systolic, First CMR | 32.6 ml/m^2 | Standard Deviation 10.6 |
| Placebo | LV Volume Indexed to BSA | End diastolic, First CMR | 63.4 ml/m^2 | Standard Deviation 15.4 |
| Placebo | LV Volume Indexed to BSA | End systolic, Second CMR | 32.0 ml/m^2 | Standard Deviation 11.7 |
Secondary
Number of Participants With Clinical Events
Time frame: from randomization to second CMR
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoetin Alfa | Number of Participants With Clinical Events | New or worsening Congestive Heart Failur | 5 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Death | 1 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Recurrent myocardial infarction | 2 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Unstaged Percutaneous Coronary Intervention | 6 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Coronary Artery Bypass Graft | 0 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Stroke | 1 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Stent thrombosis | 3 Participants |
| Epoetin Alfa | Number of Participants With Clinical Events | Left Ventricular thrombus | 3 Participants |
| Placebo | Number of Participants With Clinical Events | Left Ventricular thrombus | 2 Participants |
| Placebo | Number of Participants With Clinical Events | New or worsening Congestive Heart Failur | 2 Participants |
| Placebo | Number of Participants With Clinical Events | Coronary Artery Bypass Graft | 1 Participants |
| Placebo | Number of Participants With Clinical Events | Death | 0 Participants |
| Placebo | Number of Participants With Clinical Events | Stent thrombosis | 0 Participants |
| Placebo | Number of Participants With Clinical Events | Recurrent myocardial infarction | 0 Participants |
| Placebo | Number of Participants With Clinical Events | Stroke | 0 Participants |
| Placebo | Number of Participants With Clinical Events | Unstaged Percutaneous Coronary Intervention | 0 Participants |
Secondary
Reticulocyte Counts
Time frame: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoetin Alfa | Reticulocyte Counts | 24 hours | 1.6 percentage of red blood cells | Standard Deviation 0.5 |
| Epoetin Alfa | Reticulocyte Counts | 14 days | 1.4 percentage of red blood cells | Standard Deviation 0.6 |
| Epoetin Alfa | Reticulocyte Counts | 48 hours | 1.8 percentage of red blood cells | Standard Deviation 0.5 |
| Epoetin Alfa | Reticulocyte Counts | 30 days | 1.2 percentage of red blood cells | Standard Deviation 0.6 |
| Epoetin Alfa | Reticulocyte Counts | Baseline | 1.4 percentage of red blood cells | Standard Deviation 0.5 |
| Placebo | Reticulocyte Counts | 30 days | 1.3 percentage of red blood cells | Standard Deviation 0.7 |
| Placebo | Reticulocyte Counts | Baseline | 1.3 percentage of red blood cells | Standard Deviation 0.5 |
| Placebo | Reticulocyte Counts | 24 hours | 1.3 percentage of red blood cells | Standard Deviation 0.6 |
| Placebo | Reticulocyte Counts | 48 hours | 1.3 percentage of red blood cells | Standard Deviation 0.5 |
| Placebo | Reticulocyte Counts | 14 days | 1.4 percentage of red blood cells | Standard Deviation 0.8 |
Secondary
Vital Signs
Time frame: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoetin Alfa | Vital Signs | SBP, baseline | 129.7 mmHg | Standard Deviation 17.9 |
| Epoetin Alfa | Vital Signs | SBP at 24 hours | 118.7 mmHg | Standard Deviation 19.1 |
| Epoetin Alfa | Vital Signs | SBP at 48 hours | 114.3 mmHg | Standard Deviation 18.3 |
| Epoetin Alfa | Vital Signs | SBP, 14 days | 119.2 mmHg | Standard Deviation 18.9 |
| Epoetin Alfa | Vital Signs | SBP, 30 days | 117.4 mmHg | Standard Deviation 16.3 |
| Epoetin Alfa | Vital Signs | DBP, baseline | 78.5 mmHg | Standard Deviation 12.7 |
| Epoetin Alfa | Vital Signs | DBP, 24 hours | 70.5 mmHg | Standard Deviation 12.9 |
| Epoetin Alfa | Vital Signs | DBP, 48 hours | 68.0 mmHg | Standard Deviation 11.5 |
| Epoetin Alfa | Vital Signs | DBP, 14 days | 71.2 mmHg | Standard Deviation 10.9 |
| Epoetin Alfa | Vital Signs | DBP, 30 days | 71.0 mmHg | Standard Deviation 10.3 |
| Placebo | Vital Signs | DBP, 48 hours | 67.9 mmHg | Standard Deviation 11.5 |
| Placebo | Vital Signs | SBP, baseline | 126.2 mmHg | Standard Deviation 18.7 |
| Placebo | Vital Signs | DBP, baseline | 75.8 mmHg | Standard Deviation 13.8 |
| Placebo | Vital Signs | SBP at 24 hours | 112.9 mmHg | Standard Deviation 16.7 |
| Placebo | Vital Signs | DBP, 30 days | 71.3 mmHg | Standard Deviation 10.8 |
| Placebo | Vital Signs | SBP at 48 hours | 114.3 mmHg | Standard Deviation 16.3 |
| Placebo | Vital Signs | DBP, 24 hours | 66.3 mmHg | Standard Deviation 11 |
| Placebo | Vital Signs | SBP, 14 days | 115.2 mmHg | Standard Deviation 14.3 |
| Placebo | Vital Signs | DBP, 14 days | 69.2 mmHg | Standard Deviation 9.8 |
| Placebo | Vital Signs | SBP, 30 days | 117.9 mmHg | Standard Deviation 16.5 |