Trial in Subjects Undergoing Cardiac Catheterization With Planned Percutaneous Coronary Intervention With Stenting
- Conditions
- Coronary Artery Disease
- Interventions
- Registration Number
- NCT00357968
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to provide information of the relative potency of prasugrel and clopidogrel on platelet function studies, inflammation, and myocyte necrosis in subjects undergoing elective percutaneous coronary intervention (PCI).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 201
-
Subjects greater than or equal to 18 years of age undergoing cardiac catheterization with planned percutaneous coronary intervention (if coronary anatomy is suitable) for an indication of chest pain +/or anginal equivalent felt by the treating physician to be related to coronary ischemia.
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At least one of the following (a through c):
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Functional study (exercise, or pharmacologic) within the past 8 weeks consistent with ischemia as manifested by at least one of the following:
- A reversible defect on nuclear imaging.
- A reversible wall-motion abnormality by echocardiography.
- Horizontal or down-sloping ST-depressions greater than 1 mm on electrocardiogram (ECG) (if no imaging performed).
-
Prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)].
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A cardiac catheterization with at least one coronary artery lesion amenable to PCI (not yet performed) within 14 days prior to enrollment.
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- Known creatine kinase-myocardial bands (CK-MB)or cardiac troponin greater than the upper limit of normal at time of screening
- Planned PCI for acute myocardial infarction (MI) or planned PCI within 48 hours of fibrinolytic therapy for ST segment elevation myocardial infarction (STEMI)
- Have cardiogenic shock at the time of screening (systolic blood pressure 90 mm Hg associated with clinical evidence of end-organ hypoperfusion, or subjects requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion).
- Refractory ventricular arrhythmias
- Have New York Heart Association Class IV congestive heart failure
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Clopidogrel to Prasugrel Placebo for Clopidogrel One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days. Prasugrel to Clopidogrel Placebo for Prasugrel One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days. Prasugrel to Clopidogrel Placebo for Clopidogrel One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days. Clopidogrel to Prasugrel Placebo for Prasugrel One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days. Prasugrel to Clopidogrel Prasugrel One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days. Prasugrel to Clopidogrel Clopidogrel One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days. Clopidogrel to Prasugrel Prasugrel One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days. Clopidogrel to Prasugrel Clopidogrel One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days.
- Primary Outcome Measures
Name Time Method Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose 6 hours after loading dose IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 6 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment after 14 days of maintenance dosing Measures IPA during maintenance dosing before and after cross-over for each therapy.
IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 14 days after study drug treatment\]/\[MPA before drug treatment\]) x 100.
- Secondary Outcome Measures
Name Time Method Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose 2 hours after loading dose IPA was defined as (1 - \[maximal platelet aggregation (MPA) at 2 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the First Maintenance Dose Phase after 14 days of treatment (before cross-over) Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin \>=5 gm/dL.
Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin \>=3 gm/dL but \<5 gm/dL.Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the Crossover Maintenance Dose Phase 14 days after cross-over Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin \>=5 gm/dL.
Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin \>=3 gm/dL but \<5 gm/dL.Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase after 14 days of treatment (before cross-over) Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization
Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase 14 days after cross-over Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization
Number of Hyporesponsive Participants at 6 Hours After the Loading Dose 6 hours after loading dose Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%
Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase From loading dose to day 15 Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%
Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase 14 days after cross-over Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose 2 hours after loading dose VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose 6 hours after loading dose VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose 18 to 24 hours after loading dose VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean flourescence index. A lower PRI indicates greater antiplatelet effect.
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment after 14 days of maintenance dosing VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose 6 hours after loading dose Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose 18 to 24 hours after loading dose Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis.
Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose 6 hours after loading dose Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis.
Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose 18 to 24 hours after loading dose Mean troponin level at 18 to 24 hours after the loading dose. Troponin is a biomarker for myonecrosis.
Trial Locations
- Locations (1)
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇮🇱Tel Hashomer, Israel