Reduction of composite cardio-vascular end-point in patients who have successfully undergone elective percutaneous coronary intervention with placement of at least one drug-eluting stent.
Conditions
Interventions
Product Name: Prasugrel
Product Code: LY640315
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Prasugrel
CAS Number: 389574-19-0
Current Sponsor code: LY640315
Other descriptive name: CS-
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Subjects with coronary artery disease and clinical indication for PCI with implantation of at least one DES, and in whom PCI of all treated lesions is successful (diameter stenosis 208, measured 2 to 7 hours after a clopidogrel MD received the morning after successful PCI. [4] Aspirin use prior to PCI: A non-study-related dose of at least 250-mg (IV or oral) within 24 hours prior to PCI, and the time of PCI. [5] Only stents that are CE marked for approval may be used in this study. [6] PCI must have been performed with unfractionated or low molecular weight heparin, or bivalirudin as the procedural antithrombin. [7] Are of a legal age (and at least 18 years of age) and competent mental condition to provide written informed consent before entering the study. Informed consent must be signed by the study participant or authorized representative, according to local rules and regulations. [8] For women of child-bearing potential only (that is, women who are not surgically or chemically sterilized and who are between menarche and 1 year postmenopause), test negative for pregnancy (based on a urine or serum pregnancy test to be performed before randomization) and agree to use a reliable method of birth control (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [9] Subjects with non-ST-segment elevation myocardial infarction (NSTEMI) within 14 days prior to randomization. NSTEMI is defined as a history of chest discomfort or ischemic symptoms of =10 minutes duration at rest, with no evidence of persistent ST-segment elevation and with troponin T or I greater than the upper limit of normal (ULN). [10] Subjects with ST-segment elevation myocardial infarction (STEMI) within 14 days prior to randomization. STEMI is defined as a history of chest discomfort or ischemic symptoms of >20 minutes duration at rest with one of the following present on at least one ECG prior to PCI: (a) ST-segment elevation =1 mm in two or more contiguous ECG leads. (b) New or presumably new left bundle branch block (LBBB). (c) ST-segment depression =1 mm in two anterior precordial leads (V1 through V4) with clinical history and evidence suggestive of true posterior infarction. [11] Subjects with known major complications after PCI and prior to randomization defined as: (a) ST-segment elevation myocardial infarction (STEMI). (b) Stent thrombosis. (c) Large non-ST-segment elevation myocardial infarction (NSTEMI) defined as an increase in CK >5 x ULN with concomitant rise in CK-MB. (d) Major bleeding at the vascular access site (drop in Hgb of =5g/dL or requiring transfusion). (e) False aneurysma. [12] Have cardiogenic shock at the time of randomization (systolic blood pressure 1.5 at the time of evaluation. [22] Have a platelet count of 80 years. [26] Have received GPIIb/IIIa inhibitors eptifibatide or tirofiban within 24 hours before or during PCI or abciximab within 10 days before or during PCI. [27] Are receiving or will receive oral anticoagulation or other antiplatelet therapy besides aspirin that cannot be safely discontinued for the duration of the study. [28] Are receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued or are anticipated to require >2 weeks of daily treatment with NSAID or COX2 inhibitors during the study. [29] Are employed by Eli Lilly and Company, Ube Industries Limited, or Daiichi Sankyo Company, Ltd. [30] Investigator site, ARO or CRO personnel directly affiliated with this study and/or their immediate families.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the relative risk of the composite endpoint of Clinical Events Committee (CEC) adjudicated cardiovascular (CV) death or myocardial infarction (MI) through 6 months of maintenance treatment with prasugrel plus aspirin compared to clopidogrel plus aspirin after loading with 600-mg clopidogrel and successful elective PCI with placement of at least one drug-eluting stent (DES) in subjects with high platelet reactivity as assessed by the VerifyNow® device (P2Y12 reaction units [PRU] >208) after the first MD (75-mg) of clopidogrel. The intent of this study is to demonstrate that prasugrel is superior to clopidogrel in preventing the composite endpoint in this population. ;Secondary Objective: Efficacy To compare prasugrel with clopidogrel through 6 months: risk of CV death, MI, or UTVR; CV death, MI, or stroke; CV death, MI, stroke, or rehospitalization for cardiac ischemic events; definite or probable stent thrombosis according to ARC criteria; all cause death or MI; all cause death, MI, or UTVR... Safety To evaluate the incidence of non-CABG surgery-related TIMI Study Group major bleeding, of life-threatening bleeding, of non-CABG-related TIMI major or TIMI minor bleeding, to evaluate safety based on clinical findings, laboratory values, and the occurrence of TEAEs Pharmacodynamic To demonstrate a lower risk of the composite endpoint of CV death or MI in subjects with lower platelet reactivity To compare intrasubject and intersubject variability in platelet aggregation. To assess the incidence of bleeding events by degree of platelet aggregation Genetic Variation in DNA related to drug metabolism and transport ;Primary end point(s): The primary endpoint is the composite of CV death or MI in the ITT population(defined as all randomized subjects). The primary analysis will be the time from randomization to the onset of the first occurrence of the primary endpoint using a two-sided log-rank test. Corresponding survival curves will be esti | — |
Countries
Germany
Outcome results
None listed