A Comparison of Antiplatelet Therapies in Asian Subjects With Acute Coronary Syndrome

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00830960
First received: January 27, 2009
Last updated: September 22, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Prasugrel
Drug: Clopidogrel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Comparison of Platelet Inhibition Following Prasugrel or Clopidogrel Administration in Asian Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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. [ Time Frame: At 30 minutes, 2 hours, and 4 hours following LD administration ] [ Designated as safety issue: No ]

    Efficacy analyses analyzed and presented separately for LD and maintenance dose (MD) phase. Analysis compares PRU for prasugrel LDs (30 mg and 60 mg) with clopidogrel 300-mg LD at 30 minutes post-LD.

    Data for Primary Cohort at 4 hours post-LD, already presented in first Primary Outcome Measure, are also presented here.

    ADP-induced PRU serves as biomarker of clinical efficacy, with lower values indicating greater P2Y12 platelet inhibition.

    Observed PRU values presented with statistical comparisons of least-squares mean (LS mean) difference between prasugrel and clopidogrel.


  • 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 [ Time Frame: At 30 Days and 90 days during MD therapy ] [ Designated as safety issue: No ]

    Efficacy analyses analyzed and presented separately for loading dose (LD) and MD phase. Analysis compares PRU for 3 prasugrel MDs (10 mg, 7.5 mg, and 5 mg) with clopidogrel 75-mg MD at 30 days post-MD.

    Data for Primary Cohort at 30 days post-LD, already presented in second Primary Outcome Measure, are also presented here.

    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 least squares (LS) mean difference between prasugrel and clopidogrel.


  • 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 [ Time Frame: 30 minutes, 2 hours, and 4 hours following LD administration ] [ Designated as safety issue: No ]
    A higher percentage (percent inhibition least squares mean [LS mean]) represents greater platelet inhibition.

  • 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 [ Time Frame: 30 days and at 90 days during MD therapy ] [ Designated as safety issue: No ]
    A higher percentage (percent inhibition least squares mean [LS mean]) represents greater platelet inhibition.

  • Summary of Myocardial Infarction (MI), Stroke, Stent Thrombosis and Urgent Target Vessel Revascularization (UTVR) in Primary Cohort and Low Weight/Elderly Cohort [ Time Frame: Randomization through end of study (90 days) ] [ Designated as safety issue: No ]

    Nonfatal MI: American College of Cardiology (ACC) definition Nonfatal stroke: rapid onset of new, persistent neurologic deficit lasting >24 hours; classified as either ischemic or hemorrhagic based on imaging data, if available, or uncertain cause if imaging data was not available.

    Stent thrombosis: defined as definite, probable, or possible, based on Academic Research Consortium definitions.

    UTVR: percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for recurrent ischemia. Revascularization must have included the vessel(s) dilated at the initial procedure


  • Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Non-fatal Stroke [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]

    Risk was defined as the number of participants with events of CV death, nonfatal MI, or nonfatal stroke.

    CV death: death caused by CV event or not clearly attributable to non-CV causes.

    Nonfatal MI: per adapted American College of Cardiology definition.

    Nonfatal stroke: rapid onset of new, persistent neurologic deficit lasting more than 24 hours; either ischemic or hemorrhagic based on imaging data, if available, or uncertain cause if imaging data was not available.

    As a consequence of the overall low number of reported clinical events, composite endpoints were not analyzed.


  • Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]

    Risk was defined as the number of participants with events of CV death, nonfatal MI, or UTVR.

    UTVR: percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for recurrent ischemia. Revascularization must have included the vessel(s) dilated at the initial procedure.

    As a consequence of the overall low number of reported clinical events, composite endpoints were not analyzed.


  • Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Recurrent Myocardial Ischemia Requiring Hospitalization [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]

    Risk was defined as the number of events of CV death, nonfatal MI, nonfatal stroke or recurrent myocardial ischemia requiring hospitalization.

    Recurrent myocardial ischemia requiring hospitalization: rehospitalization for symptoms of myocardial ischemia at rest with either new ST-segment deviation ≥1 mm, or performance of a coronary revascularization procedure percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) during the same hospital stay.

    As a consequence of the overall low number of reported clinical events, composite endpoints were not analyzed.


  • Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Urgent Target Vessel Revascularization (UTVR), or Recurrent Myocardial Ischemia Requiring Hospitalization (Analyzed Individually) [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]
    Risk was defined as the number of participants with events of CV death, nonfatal MI, nonfatal stroke, UTVR, or recurrent myocardial ischemia requiring hospitalization.

  • Risk of Definite or Probable Stent Thrombosis Per ARC (Academic Research Consortium) Definition [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]

    Risk was defined as the number of participants with events of definite or probable stent thrombosis.

    As a consequence of the overall low number of reported clinical events, composite endpoints were not analyzed.


  • Risk of Definite, Probable, or Possible Stent Thrombosis Per Academic Research Consortium (ARC) Definition [ Time Frame: 90 days ] [ Designated as safety issue: No ]

    Risk was defined as the number of participants with events of definite, probable, or possible stent thrombosis.

    As a consequence of the overall low number of reported clinical events, composite endpoints were not analyzed.


  • Risk of All-cause Death in Primary Cohort and Low Weight/Elderly Cohort [ Time Frame: Randomization through end of study (90 days) ] [ Designated as safety issue: No ]
    Risk was defined as the number of participants with events of all-cause death.

  • 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 [ Time Frame: Randomization through end of study (90 days) ] [ Designated as safety issue: Yes ]

    Bleeding events were classified and analyzed in accordance with the TIMI criteria definitions.

    Major bleeding: any intracranial hemorrhage (ICR) OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 grams/deciliter (gm/dL) from baseline.

    Minor bleeding: any clinically overt bleeding associated with a fall in Hgb of ≥3 but <5 gm/dL from baseline.

    Insignificant bleeding: any bleeding event that does not meet criteria for a Major or Minor bleed.


  • Incidence of CABG-related TIMI Major or Minor Bleeding. [ Time Frame: Randomization through end of study (90 days) ] [ Designated as safety issue: Yes ]
  • Inpatient Healthcare Resource Utilization [ Time Frame: Initial hospitalization, 30 days, 90 days ] [ Designated as safety issue: No ]
    Healthcare resource utilization data were modeled from historical analyses to determine initial hospitalization costs, total 30-day medical care costs, and total 90-day medical care costs.

  • Genetic Variation Related to Drug Metabolism and Transport Substudy Result Summary [ Time Frame: Baseline to 4 hours post-loading dose (LD), 30 days and 90 days during maintenance dose (MD) phase ] [ Designated as safety issue: No ]

    The primary hypothesis for the genetics substudy was that CYP2C19 genetic variation has a significant effect on pharmacodynamic (PD) response to clopidogrel but not on PD response to prasugrel per change in PRU as measured by the Accumetrics VerifyNow P2Y12 device.

    Participants were classified by CYP2C19 genotype into predicted metabolic phenotypes according to literature-based functional predictions. These classifications were clustered into 2 groups: extensive metabolizer (EM) and reduced metabolizer (RM).

    A higher value for change in PRU indicates a greater level of platelet inhibition.


  • Risk of CV Death, Nonfatal MI, Nonfatal Stroke, UTVR, or Recurrent Myocardial Ischemia Requiring Hospitalization (Analyzed Individually) [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]
    Risk of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Urgent Target Vessel Revascularization (UTVR), or Recurrent Myocardial Ischemia Requiring Hospitalization (Analyzed Individually)


Enrollment: 720
Study Start Date: February 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prasugrel 60/10 Primary
Loading dose 60 mg followed by maintenance dose 10 mg/day
Drug: Prasugrel
Oral, daily, 90 days
Other Names:
  • LY640315
  • Effient
  • Efient
  • CS-747
Experimental: Prasugrel 30/7.5 Primary
Loading dose 30 mg followed by maintenance dose 7.5 mg/day
Drug: Prasugrel
Oral, daily, 90 days
Other Names:
  • LY640315
  • Effient
  • Efient
  • CS-747
Experimental: Prasugrel 30/5 Primary
Loading dose 30 mg followed by maintenance dose 5 mg/day
Drug: Prasugrel
Oral, daily, 90 days
Other Names:
  • LY640315
  • Effient
  • Efient
  • CS-747
Active Comparator: Clopidogrel 300/75 Primary
Loading dose 300 mg followed by maintenance dose 75 mg/day
Drug: Clopidogrel
Oral, daily, 90 days
Other Name: Plavix
Experimental: Prasugrel 30/5 Low Weight/Elderly
Loading dose 30 mg followed by maintenance dose 5 mg/day
Drug: Prasugrel
Oral, daily, 90 days
Other Names:
  • LY640315
  • Effient
  • Efient
  • CS-747
Active Comparator: Clopidogrel 300/75 Low Weight/Elderly
Loading dose 300 mg followed by maintenance dose 75 mg/day
Drug: Clopidogrel
Oral, daily, 90 days
Other Name: Plavix

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00830960

Locations
China
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Beijing, China, 100853
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Guang Zhou, China, 510080
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Hangzhou, China, 310009
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Nanjing, China, 210008
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Shanghai, China, 200433
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Shenyang, China, 110016
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Wenzhou, China, 325027
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Xi'An, China, 710061
Korea, Republic of
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Daegu, Korea, Republic of, 700-721
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Kwang Ju, Korea, Republic of, 501-757
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Seongnam-Si, Korea, Republic of, 463-707
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Seoul, Korea, Republic of, 135 720
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Suwon-City, Korea, Republic of, 442-721
Taiwan
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Taichung, Taiwan, 404
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Taichung City, Taiwan, 40201
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Taipei, Taiwan, 112
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Tao-Yuan, Taiwan, 333
Thailand
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Bangkok, Thailand, 10400
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Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Eli Lilly and Company
Daiichi Sankyo Co., Ltd.
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00830960     History of Changes
Other Study ID Numbers: 11299, H7T-MC-TACE
Study First Received: January 27, 2009
Results First Received: June 17, 2011
Last Updated: September 22, 2011
Health Authority: China: Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Department of Health
Thailand: Food and Drug Administration
Singapore: Health Sciences Authority

Additional relevant MeSH terms:
Acute Coronary Syndrome
Syndrome
Angina Pectoris
Cardiovascular Diseases
Chest Pain
Disease
Heart Diseases
Myocardial Ischemia
Pain
Pathologic Processes
Signs and Symptoms
Vascular Diseases
Clopidogrel
Prasugrel
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014