Trial in Subjects Undergoing Cardiac Catheterization With Planned Percutaneous Coronary Intervention With Stenting

Eli Lilly and Company201 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

201

Conditions

Coronary Artery Disease

Interventions

PrasugrelDRUG

Administered orally

ClopidogrelDRUG

Administered orally

Placebo for PrasugrelDRUG

Administered orally

Placebo for Clopidogrel

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. * At least one of the following (a through c): 1. Functional study (exercise, or pharmacologic) within the past 8 weeks consistent with ischemia as manifested by at least one of the following: 1. A reversible defect on nuclear imaging. 2. A reversible wall-motion abnormality by echocardiography. 3. Horizontal or down-sloping ST-depressions greater than 1 mm on electrocardiogram (ECG) (if no imaging performed). 2. Prior coronary revascularization \[percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)\]. 3. A cardiac catheterization with at least one coronary artery lesion amenable to PCI (not yet performed) within 14 days prior to enrollment. Exclusion Criteria: * 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

Locations (16)

Outcomes

Primary Outcomes

Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose

IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 6 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.

Time frame: 6 hours after loading dose

Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment

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.

Time frame: after 14 days of maintenance dosing

Secondary Outcomes

Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose

IPA was defined as (1 - \[maximal platelet aggregation (MPA) at 2 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.

Time frame: 2 hours after loading dose

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

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.

Time frame: after 14 days of treatment (before cross-over)

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

Data from ClinicalTrials.gov

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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.

Jacksonville, Florida, United States

Worcester, Massachusetts, United States

Ann Arbor, Michigan, United States

Rapid City, South Dakota, United States

Lille, France

Marseille, France

Paris, France

Tours, France

Bad Krozingen, Germany

Berlin, Germany

...and 6 more locations

Time frame: 14 days after cross-over

Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase

Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization

Time frame: after 14 days of treatment (before cross-over)

Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase

Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization

Time frame: 14 days after cross-over

Number of Hyporesponsive Participants at 6 Hours After the Loading Dose

Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%

Time frame: 6 hours after loading dose

Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase

Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%

Time frame: From loading dose to day 15

Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase

Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%

Time frame: 14 days after cross-over

Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the 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.

Time frame: 2 hours after loading dose

Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose

Time frame: 6 hours after loading dose

Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the 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.

Time frame: 18 to 24 hours after loading dose

Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment

Time frame: after 14 days of maintenance dosing

Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose

Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis

Time frame: 6 hours after loading dose

Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose

Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis.

Time frame: 18 to 24 hours after loading dose

Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose

Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis.

Time frame: 6 hours after loading dose

Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose

Mean troponin level at 18 to 24 hours after the loading dose. Troponin is a biomarker for myonecrosis.

Time frame: 18 to 24 hours after loading dose