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

August 25, 2010 updated by: Eli Lilly and Company

Protocol H7T-MC-TABL(a) PRasugrel IN Comparison to Clopidogrel for Inhibition of PLatelet Activation and AggrEgation (PRINCIPLE) - TIMI 44

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 Overview

Study Type

Interventional

Enrollment (Actual)

201

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Lille, France, 59037
        • 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.
      • Marseille, France, 13385
        • 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.
      • Paris, France, 75013
        • 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.
      • Tours, France, 37044
        • 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.
      • Bad Krozingen, Germany, D-79189
        • 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.
      • Berlin, Germany, D-12203
        • 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.
      • Giessen, Germany, 35392
        • 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.
      • München, Germany, D-80636
        • 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.
      • Tubingen, Germany, 72076
        • 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.
      • Haifa, Israel, 31096
        • 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.
      • Jerusalem, Israel, 91120
        • 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, 52621
        • 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.
    • Florida
      • Jacksonville, Florida, United States, 32209
        • 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.
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • 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.
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • 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.
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • 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.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prasugrel to 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.
Administered orally
Other Names:
  • Effient
  • Efient
  • LY 640315
Administered orally
Administered orally
Administered orally
Active Comparator: Clopidogrel to 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.
Administered orally
Other Names:
  • Effient
  • Efient
  • LY 640315
Administered orally
Administered orally
Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose
Time Frame: 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.
6 hours after loading dose
Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment
Time Frame: 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.

after 14 days of maintenance dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose
Time Frame: 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.
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
Time Frame: 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.

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
Time Frame: 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.

14 days after cross-over
Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase
Time Frame: 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
after 14 days of treatment (before cross-over)
Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase
Time Frame: 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
14 days after cross-over
Number of Hyporesponsive Participants at 6 Hours After the Loading Dose
Time Frame: 6 hours after loading dose
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%
6 hours after loading dose
Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase
Time Frame: From loading dose to day 15
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%
From loading dose to day 15
Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase
Time Frame: 14 days after cross-over
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%
14 days after cross-over
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose
Time Frame: 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.
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
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.
6 hours after loading dose
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose
Time Frame: 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.
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
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.
after 14 days of maintenance dosing
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose
Time Frame: 6 hours after loading dose
Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis
6 hours after loading dose
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose
Time Frame: 18 to 24 hours after loading dose
Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis.
18 to 24 hours after loading dose
Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose
Time Frame: 6 hours after loading dose
Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis.
6 hours after loading dose
Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose
Time Frame: 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.
18 to 24 hours after loading dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimate)

July 28, 2006

Study Record Updates

Last Update Posted (Estimate)

August 31, 2010

Last Update Submitted That Met QC Criteria

August 25, 2010

Last Verified

August 1, 2010

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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