Acute Coronary Syndrome, Myocardial Ischemia
Conditions
Keywords
myocardial infarction, acute coronary syndrome, non-ST-segment elevation, eptifibatide, Integrilin, glycoprotein IIb/IIIa inhibitor (GP IIb/IIIa), percutaneous coronary intervention (PCI), coronary artery bypass graph surgery (CABG), catheterization, angina, ischemia, cardiac ischemia, cardiovascular disease
Brief summary
The purpose of this study is to see if early INTEGRILIN® (eptifibatide) therapy in patients with non-ST-segment elevation acute coronary syndrome (ACS) reduces the occurence of death, heart attack and urgent cardiac intervention (surgery) compared to placebo (with delayed provisional use of eptifibatide).
Detailed description
This study will enroll patients who experience symptoms of acute coronary syndrome (experiencing chest pain at rest with episodes lasting at least 10 minutes) and who are planned to undergo invasive surgical procedures after being given study drug for 12 to 96 hours. There are two different treatment groups in this study; approximately half of the patients will go to each group and the likelihood of receiving study drug vs. placebo is 50/50 (like tossing a coin). Medications that are standard of care will be provided to the patients (all patients will be given aspirin and standard hospital doses of one of two other blood thinning drugs - unfractionated heparin (UFH) or low-molecular-weight heparin). Which one patients receive is at the discretion of the Investigator.
Interventions
intravenous; 180 mcg/kg bolus followed by infusion of 2 mcg/kg/min for 12 to 96 hours (or longer if necessary to complete the 18- to 24-hour post-PCI infusion period, or up to 120 hours in patients who proceed to CABG \[coronary artery bypass graft\]); second bolus of 180 mcg/kg administered 10 minutes after first bolus.
DRUGPlacebo
intravenous; delivery to match eptifibatide to maintain blind
Sponsors
Duke Clinical Research Institute
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to give informed consent and comply with study procedures and follow-up through 1 year. * Plan to undergo an invasive strategy after receiving study drug for 12 to 96 hours. * Able to be randomized into the trial within 12 hours of having symptoms of acute coronary syndrome. * Experiencing symptoms of cardiac ischemia at rest (angina or anginal equivalent) with episode(s) lasting at least 10 minutes and have at least 2 of the following: * 60 years of age or more * Electrocardiogram changes (ECG) * Elevated troponin (protein released in the blood stream in people suffering from acute coronary syndrome) or CK-MB levels * Or have all 3 of the following: * Prior history of cardiovascular disease * Elevated troponin or CK-MB levels * 50-59 years of age
Exclusion criteria
* pregnancy (known or suspected) * renal dialysis within 30 days prior to randomizing in study * other serious illnesses or any condition that the investigator feels would pose a significant hazard to the patient if the investigational therapy was to be initiated * Stroke (hemorrhagic stroke at any time or non-hemorrhagic stroke within previous 7 days), central nervous system damage (such as neoplasm, aneurysm, intracranial surgery), bleeding disorders (including gastrointestinal bleeding), or recent major surgery or major trauma. * History of certain hematologic problems following treatment with heparin or eptifibatide. * Therapy with certain related drugs within a short time before randomization into the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of the Composite of Death, Myocardial Infarction (MI), Recurrent Ischemia Requiring Urgent Revascularization (RI-UR), and Thrombotic Bail-out. | 96 hours after randomization |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of the Composite of Death/MI. | 30 days after randomization |
Participant flow
Pre-assignment details
Patients in both treatment groups who were undergoing PCI could receive unblinded eptifibatide provisionally immediately before or during percutaneous coronary intervention (PCI) at the discretion of the investigator.
Participants by arm
| Arm | Count |
|---|---|
| Eptifibatide Eptifibatide in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin. | 4,722 |
| Placebo Placebo in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin. | 4,684 |
| Total | 9,406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Bleeding | 0 | 2 |
| Overall Study | Consent Withdrawn | 11 | 14 |
| Overall Study | Exclusion criteria met | 6 | 6 |
| Overall Study | Missing | 4 | 2 |
| Overall Study | Not otherwise specified | 4 | 8 |
| Overall Study | Physician Decision | 3 | 7 |
| Overall Study | Surgery | 0 | 1 |
| Overall Study | Technical reason | 7 | 2 |
Baseline characteristics
| Characteristic | Eptifibatide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 10.6 | 66.7 years STANDARD_DEVIATION 10.7 | 66.6 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 1513 Participants | 1462 Participants | 2975 Participants |
| Sex: Female, Male Male | 3209 Participants | 3222 Participants | 6431 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4,686 | 0 / 4,643 |
| serious Total, serious adverse events | 66 / 4,686 | 60 / 4,643 |
Outcome results
Primary
Incidence of the Composite of Death, Myocardial Infarction (MI), Recurrent Ischemia Requiring Urgent Revascularization (RI-UR), and Thrombotic Bail-out.
Time frame: 96 hours after randomization
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eptifibatide | Incidence of the Composite of Death, Myocardial Infarction (MI), Recurrent Ischemia Requiring Urgent Revascularization (RI-UR), and Thrombotic Bail-out. | 9.3 percentage of participants |
| Placebo | Incidence of the Composite of Death, Myocardial Infarction (MI), Recurrent Ischemia Requiring Urgent Revascularization (RI-UR), and Thrombotic Bail-out. | 10.0 percentage of participants |
Secondary
Incidence of the Composite of Death/MI.
Time frame: 30 days after randomization
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eptifibatide | Incidence of the Composite of Death/MI. | 11.2 percentage of participants |
| Placebo | Incidence of the Composite of Death/MI. | 12.3 percentage of participants |