A Comparison of Platelet Inhibition Following Prasugrel or Clopidogrel Administration in Asian Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 720
- Locations
- 1
- Primary Endpoint
- Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-mediated Platelet Aggregation (P2Y12 Reaction Units; PRU) Using the Accumetrics VerifyNow (VN) P2Y12 Assay at 4 Hours Post-Loading Dose (LD) in Primary Cohort (≥60 kg and <75 Years)
Study Overview
Brief Summary
The study will compare the safety and efficacy of prasugrel, administered at different doses with clopidogrel in the treatment of Asian participants with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •A person who has been diagnosed with acute coronary syndrome (ACS) and is to undergo a percutaneous coronary intervention (PCI)
- •A person who is of East or Southeast Asian descent
- •A person who is of the legal age of 18 (or age 21 in Singapore) and is mentally competent to provide a signed written informed consent before entering the study
- •If a woman is of childbearing potential, she must test negative for pregnancy and agree to use a reliable method of birth control
Exclusion Criteria
- •A person who has a severe cardiovascular condition such as cardiogenic shock at the time of randomization, ventricular arrhythmias or congestive heart failure
- •A person who is at an increased risk of bleeding (e.g. active internal bleeding, history of bleeding disorder, recent fibrinolytic therapy before randomization into the study)
- •A person who has prior history of any one of the following: ischemic or hemorrhagic stroke; intracranial neoplasm, arteriovenous malformation, or aneurysm; prior history of transient ischemic attack (TIA)
- •A person who needs to take other antiplatelet therapy other than Aspirin for the duration of the study
- •A person who receives daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued
- •A person who has a severe liver disease, such as cirrhosis
- •A person who has a condition such as alcoholism, mental illness, or drug dependence
Arms & Interventions
Prasugrel 60/10 Primary
Loading dose 60 mg followed by maintenance dose 10 mg/day
Intervention: Prasugrel (Drug)
Prasugrel 30/7.5 Primary
Loading dose 30 mg followed by maintenance dose 7.5 mg/day
Intervention: Prasugrel (Drug)
Prasugrel 30/5 Primary
Loading dose 30 mg followed by maintenance dose 5 mg/day
Intervention: Prasugrel (Drug)
Clopidogrel 300/75 Primary
Loading dose 300 mg followed by maintenance dose 75 mg/day
Intervention: Clopidogrel (Drug)
Prasugrel 30/5 Low Weight/Elderly
Loading dose 30 mg followed by maintenance dose 5 mg/day
Intervention: Prasugrel (Drug)
Clopidogrel 300/75 Low Weight/Elderly
Loading dose 300 mg followed by maintenance dose 75 mg/day
Intervention: Clopidogrel (Drug)
Outcomes
Primary Outcomes
Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-mediated Platelet Aggregation (P2Y12 Reaction Units; PRU) Using the Accumetrics VerifyNow (VN) P2Y12 Assay at 4 Hours Post-Loading Dose (LD) in Primary Cohort (≥60 kg and <75 Years)
Time Frame: At 4 hours following LD administration
ADP-induced PRU represents the rate and extent of ADP-stimulated platelet aggregation and serves as a biomarker of clinical efficacy, with lower values indicating greater P2Y12 platelet inhibition. Observed PRU values are presented with statistical comparisons of difference in least squares mean (LS mean) PRU values between prasugrel and clopidogrel. Efficacy analyses are analyzed and presented separately for the LD and maintenance dose (MD) phase.
Adenosine Diphosphate (ADP)-Induced P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNow (VN) P2Y12 Assay at 30 Days During Maintenance Dose (MD) Administration in Primary Cohort
Time Frame: At 30 days during MD therapy
Efficacy analyses are analyzed and presented separately for the loading dose (LD) and MD phase. This primary outcome analysis compares PRU for the 3 prasugrel MDs (10 mg, 7.5 mg, and 5 mg) with the clopidogrel 75-mg MD at 30 days post-MD in the primary cohort (participants who weighed ≥60 kg and were \<75 years). ADP-induced PRU serves as a biomarker of clinical efficacy, with lower values indicating greater P2Y12 platelet inhibition. Observed PRU values are presented with statistical comparisons of LS mean difference between prasugrel and clopidogrel.
Secondary Outcomes
- Percent Inhibition of Adenosine Diphosphate (ADP)-Induced P2Y12 Reaction Units (PRU) During the Maintenance Dose (MD) Phase at 30 Days and 90 Days in Primary Cohort and Low Weight/Elderly Cohort(30 days and at 90 days during MD therapy)
- Adenosine Diphosphate (ADP)-Induced P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNow (VN) P2Y12 Assay at 30 Minutes, 2 and 4 Hours Post-Loading Dose (LD) in Primary (≥60 kg and <75 Years) and Low Weight/Elderly (<60 kg or ≥75 Years) Cohorts.(At 30 minutes, 2 hours, and 4 hours following LD administration)
- Adenosine Diphosphate (ADP)-Induced P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNow (VN) P2Y12 Assay at During Maintenance Dose (MD) Phase at 30 Days and 90 Days in Primary Cohort and Low Weight/Elderly Cohort(At 30 Days and 90 days during MD therapy)
- Percent Inhibition of Adenosine Diphosphate (ADP)-Induced P2Y12 Reaction Units (PRU) at 30 Minutes, 2 Hours, and 4 Hours Post-Loading Dose (LD) in Primary in Primary Cohort and Low Weight/Elderly Cohort(30 minutes, 2 hours, and 4 hours following LD administration)
- Summary of Myocardial Infarction (MI), Stroke, Stent Thrombosis and Urgent Target Vessel Revascularization (UTVR) in Primary Cohort and Low Weight/Elderly Cohort(Randomization through end of study (90 days))
- Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Non-fatal Stroke(30 days and 90 days)
- Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR)(30 days and 90 days)
- Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Recurrent Myocardial Ischemia Requiring Hospitalization(30 days and 90 days)
- Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Urgent Target Vessel Revascularization (UTVR), or Recurrent Myocardial Ischemia Requiring Hospitalization (Analyzed Individually)(30 days and 90 days)
- Risk of Definite or Probable Stent Thrombosis Per ARC (Academic Research Consortium) Definition(30 days and 90 days)
- Risk of Definite, Probable, or Possible Stent Thrombosis Per Academic Research Consortium (ARC) Definition(90 days)
- Risk of All-cause Death in Primary Cohort and Low Weight/Elderly Cohort(Randomization through end of study (90 days))
- Incidence of Non-coronary Artery Bypass Graft (CABG) Related Thrombolysis in Myocardial Infarction (TIMI) Life-threatening (a Subset of Non-CABG-related TIMI Major Bleeding), Major, Minor, and Minimal Bleeding(Randomization through end of study (90 days))
- Incidence of CABG-related TIMI Major or Minor Bleeding.(Randomization through end of study (90 days))
- Inpatient Healthcare Resource Utilization(Initial hospitalization, 30 days, 90 days)
- Genetic Variation Related to Drug Metabolism and Transport Substudy Result Summary(Baseline to 4 hours post-loading dose (LD), 30 days and 90 days during maintenance dose (MD) phase)
- Risk of CV Death, Nonfatal MI, Nonfatal Stroke, UTVR, or Recurrent Myocardial Ischemia Requiring Hospitalization (Analyzed Individually)(30 days and 90 days)