Coronary Artery Disease (CAD)
Conditions
Keywords
Clopidogrel, VerifyNow, PRU Measurements, Drug Eluting Stents (DES), Heart Disease, Percutaneous Coronary Intervention (PCI), P2Y12, Platelets, Platelet Reactivity
Brief summary
To determine the efficacy of prasugrel versus clopidogrel for the reduction of adverse cardiovascular outcomes in patients with high platelet reactivity on clopidogrel after successful implantation of coronary drug-eluting stents. To determine the adverse event profile of prasugrel in patients with high platelet reactivity on clopidogrel after implantation of coronary drug-eluting stents. To determine the effect of prasugrel on inhibition of platelet activation in patients with high platelet reactivity on clopidogrel.
Interventions
DRUGPrasugrel
One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months.
DRUGClopidogrel
75 mg oral daily maintenance dose up to 6 months.
Sponsors
Daiichi Sankyo Co., Ltd.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have coronary artery disease and clinical indication for percutaneous coronary intervention (PCI) with implantation of at least one drug-eluting stent and where percutaneous coronary intervention of all treated lesions is successful. * Have been given standard-of-care clopidogrel 600-mg loading dose between 24 hours before and at the time of PCI. * Standard of Care Aspirin use prior to PCI - at least 250-mg \[intravenous (IV) or oral\] within 24 hours before PCI and at the time of PCI. * VerifyNow P2Y12 reaction units \> 208 measured 2-7 hours after clopidogrel maintenance dose the day after successful PCI.
Exclusion criteria
* Non-ST segment elevation myocardial infarction within 14 days prior to randomization * ST-segment elevation myocardial infarction within 14 days prior to randomization * Have known major complications after percutaneous coronary intervention and prior to randomization * Have a body weight \< 60 kilogram (kg) * Have cardiogenic shock at time of randomization * Have refractory ventricular arrhythmias * Have New York Heart Association Class IV congestive heart failure * Have received glycoprotein (GP) IIb/IIIa inhibitors eptifibatide or tirofiban within 24 hrs before or during percutaneous coronary intervention or abciximab within 10 days before or during percutaneous coronary intervention * Are receiving daily treatment with nonsteroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued or are anticipated to require \> 2 weeks of daily treatment during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite Endpoint of Cardiovascular Death or Myocardial Infarction (MI) | Baseline through 6 months | The endpoint in this measure is a combination of cardiovascular death or MI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stent Thrombosis (ST) | Baseline through 6 months | Academic Research Consortium (ARC) criteria was used to define ST. Definite ST is angiographic or pathologic confirmation of partial or total thrombotic occlusion within the peri-stent region, and at least one of the following additional criteria: acute ischemic symptoms; ischemic electrocardiogram changes; elevated cardiac biomarkers. Probable ST is any unexplained death within 30 days of stent implantation; any MI, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause. |
| Number of Participants With Composite Endpoint of All-Cause Death or Myocardial Infarction (MI) | Baseline through 6 months | The endpoint in this measure is a combination of all-cause death or MI. |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months | 212 |
| Clopidogrel 75 mg oral daily maintenance dose up to 6 months. | 211 |
| Total | 423 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Didn't receive any study drug | 2 | 1 |
| Overall Study | Sponsor Decision | 58 | 60 |
| Overall Study | Withdrawal by Subject | 16 | 13 |
Baseline characteristics
| Characteristic | Clopidogrel | Total | Prasugrel |
|---|---|---|---|
| Age Continuous | 66.3 years STANDARD_DEVIATION 8.6 | 66.1 years STANDARD_DEVIATION 8.4 | 65.8 years STANDARD_DEVIATION 8.3 |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized White | 207 participants | 418 participants | 211 participants |
| Region of Enrollment Germany | 198 participants | 398 participants | 200 participants |
| Region of Enrollment United States | 13 participants | 25 participants | 12 participants |
| Sex: Female, Male Female | 57 Participants | 116 Participants | 59 Participants |
| Sex: Female, Male Male | 154 Participants | 307 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 110 / 210 | 72 / 210 |
| serious Total, serious adverse events | 40 / 210 | 38 / 210 |
Outcome results
Primary
Number of Participants With Composite Endpoint of Cardiovascular Death or Myocardial Infarction (MI)
The endpoint in this measure is a combination of cardiovascular death or MI.
Time frame: Baseline through 6 months
Population: Participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Composite Endpoint of Cardiovascular Death or Myocardial Infarction (MI) | 0 participants |
| Clopidogrel | Number of Participants With Composite Endpoint of Cardiovascular Death or Myocardial Infarction (MI) | 1 participants |
Secondary
Number of Participants With Composite Endpoint of All-Cause Death or Myocardial Infarction (MI)
The endpoint in this measure is a combination of all-cause death or MI.
Time frame: Baseline through 6 months
Population: Participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Composite Endpoint of All-Cause Death or Myocardial Infarction (MI) | 0 participants |
| Clopidogrel | Number of Participants With Composite Endpoint of All-Cause Death or Myocardial Infarction (MI) | 2 participants |
Secondary
Number of Participants With Stent Thrombosis (ST)
Academic Research Consortium (ARC) criteria was used to define ST. Definite ST is angiographic or pathologic confirmation of partial or total thrombotic occlusion within the peri-stent region, and at least one of the following additional criteria: acute ischemic symptoms; ischemic electrocardiogram changes; elevated cardiac biomarkers. Probable ST is any unexplained death within 30 days of stent implantation; any MI, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause.
Time frame: Baseline through 6 months
Population: Participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Stent Thrombosis (ST) | 0 participants |
| Clopidogrel | Number of Participants With Stent Thrombosis (ST) | 0 participants |