Clopidogrel to Prasugrel in Acute Coronary Syndrome (ACS) Patients

November 15, 2012 updated by: Eli Lilly and Company

TRansferring From ClopIdogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome PatiEnTs: TRIPLET

This study will evaluate the use of a prasugrel 60 mg loading dose (LD) administered during percutaneous coronary intervention (PCI) with and without a prior LD of clopidogrel on platelet inhibition in patients presenting with acute coronary syndrome (ACS). Platelet inhibition following a prasugrel LD in clopidogrel pretreated patients' will be determined in a time-dependent manner for two different prasugrel loading doses (30 mg and 60 mg). Understanding the effects of this combination on platelet inhibition will provide guidance to physicians on the use of prasugrel in patients who have already been pretreated with clopidogrel.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

282

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

  • India
      • Bangalore, India, 560099
        • 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.
      • Hyderabaad, India, 500 001
        • 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.
      • New Delhi, India, 110 060
        • 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

14 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants hospitalized with acute coronary syndrome (ACS) [unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI)] as determined by the investigator, and who are anticipated to undergo percutaneous coronary intervention (PCI) as a treatment for the ACS event within 24 hours of the clopidogrel/placebo loading dose
  • Participants provide signed informed consent form (ICF)
  • Participants weigh at least 60 kilograms (kg) at the time of screening
  • Women of child-bearing potential (that is, women who are not surgically or chemically sterilized and who are between menarche and 1-year postmenopause), test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test

Exclusion Criteria:

  • Have cardiogenic shock at the time of randomization (systolic blood pressure greater than 90 millimeters of mercury (mm Hg) associated with clinical evidence of end-organ hypoperfusion, or participants requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion
  • Have refractory ventricular arrhythmias
  • Have New York Heart Association (NYHA) Class IV congestive heart failure
  • Have systolic blood pressure greater than 180 mm Hg, or diastolic blood pressure greater than 100 mm Hg on more than 1 assessment at any time from participant presentation of ACS treatment to enrollment
  • Have received fibrin-specific fibrinolytic therapy less than 24 hours prior to randomization
  • Have received nonfibrin-specific fibrinolytic therapy less than 48 hours prior to randomization
  • Have active internal bleeding or history of bleeding diathesis
  • Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding
  • Prior history of ischemic or hemorrhagic stroke
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Prior history of transient ischemic attack (TIA)
  • Have an International Normalized Ratio (INR) known to be greater than 1.5 at the time of evaluation
  • Have a platelet count of less than 100,000 per cubic millimeter (mm^3) at the time of evaluation
  • Have anemia [hemoglobin (Hgb) less than 10 grams per deciliter (g/dL)] at the time of evaluation
  • Have received 1 or more doses of a thienopyridine (ticlopidine, clopidogrel, or prasugrel) or other adenosine diphosphate (ADP) receptor inhibitor within 10 days prior to screening
  • Have been administered glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor within the past 7 days or planned use of a GPIIb/IIIa inhibitor during PCI
  • Are receiving or will receive oral anticoagulation or other antiplatelet therapy, other than aspirin (ASA), which cannot be safely discontinued for the duration of the study.
  • Are receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued during the study
  • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Have previously completed or withdrawn from this study or any other study investigating prasugrel
  • Are women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding
  • Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator, is associated with reduced survival over the expected treatment period
  • Have known severe hepatic dysfunction (that is, with cirrhosis or portal hypertension)
  • Have a history of intolerance or allergy to aspirin or approved thienopyridines (ticlopidine, clopidogrel or prasugrel)
  • May be unable to cooperate with protocol requirements and follow-up procedures

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: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo and 60 milligram (mg) Prasugrel
Placebo loading dose administered once orally before percutaneous coronary intervention (PCI) and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
Drug: Prasugrel
Loading dose administered once orally and maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
Other Names:
  • LY640315
Drug: Placebo
Loading dose administered once orally
Experimental: 600 mg Clopidogrel and 60 mg Prasugrel
600-mg clopidogrel loading dose administered once orally before PCI and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
Drug: Prasugrel
Loading dose administered once orally and maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
Other Names:
  • LY640315
Drug: Clopidogrel
Loading dose administered once orally.
Experimental: 600 mg Clopidogrel and 30 mg Prasugrel
600-mg clopidogrel loading dose administered once orally before PCI and 30-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
Drug: Prasugrel
Loading dose administered once orally and maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
Other Names:
  • LY640315
Drug: Clopidogrel
Loading dose administered once orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation 6 Hours After Prasugrel Loading Dose (LD)
Time Frame: 6 hours after prasugrel loading dose
ADP-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
6 hours after prasugrel loading dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation at Baseline, 2, 24 and 72 Hours After Prasugrel Loading Dose (LD)
Time Frame: Baseline and 2 hours and 24 hours and 72 hours after prasugrel loading dose
ADP-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
Baseline and 2 hours and 24 hours and 72 hours after prasugrel loading dose
Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hematocrit
Time Frame: Baseline, 72 hours
Baseline, 72 hours
Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hemoglobin
Time Frame: Baseline, 72 hours
Baseline, 72 hours
Percentage of Inhibition of Platelet Aggregation
Time Frame: Baseline and 2 and 6 and 24 and 72 hours after loading dose
Adenosine Diphosphate (ADP)-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. The internal BASE standard is an independent measurement and serves as an estimate of the participant's baseline platelet aggregation independent of P2Y12 receptor inhibition. Percent Inhibition of Platelet Aggregation=(1-[PRU/BASE) x 100%, high numbers represent increased platelet inhibition. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
Baseline and 2 and 6 and 24 and 72 hours after loading dose
Percentage of Poor Responders
Time Frame: Baseline and 2 and 6 and 24 and 72 hours after loading dose
Poor responders are those who had P2Y12 Reaction Units (PRU)≥ 240.
Baseline and 2 and 6 and 24 and 72 hours after loading dose
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: Baseline through 72 hours after prasugrel loading dose
TEAE is a worsening or new occurrence of adverse event (AE) during treatment compared to baseline. A summary of serious adverse events (SAE) and other nonserious AE are located in the Reported Adverse Events section.
Baseline through 72 hours after prasugrel loading dose
P2Y12 Reaction Units (PRU) of Clopidogrel Treated Participants at Baseline by Cytochrome P450 2C19 (CYP2C19)-Predicted Functional Groups - CYP2C19 Extensive Metabolizers (EM) and Reduced Metabolizers (RM)
Time Frame: Baseline
CYP2C19 is a drug metabolizing enzyme. CYP2C19 Extensive metabolizers (EM) are individuals with two fully active / normal function CYP2C19 alleles (*1/*1, *1/*17). CYP2C19 Reduced metabolizers (RM) are individuals with at least one reduced-function CYP2C19 allele (*2/*2, *1/*2). Least Squares (LS) Mean values were controlled for CYP2C19 genetic group.
Baseline
P2Y12 Reaction Units (PRU) at 6 Hours Post-Prasugrel Loading Dose (LD) by Cytochrome P450 2C19 (CYP2C19)-Predicted Functional Groups - Extensive Metabolizers (EM) and Reduced Metabolizers (RM)
Time Frame: 6 hours after prasugrel loading dose
CYP2C19 is a drug metabolizing enzyme. CYP2C19 Extensive metabolizers (EM) are individuals with two fully active / normal function CYP2C19 alleles (*1/*1, *1/*17). CYP2C19 Reduced metabolizers (RM) are individuals with at least one reduced-function CYP2C19 allele (*2/*2, *1/*2). Least Squares (LS) Mean values were controlled for CYP2C19 genetic group.
6 hours after prasugrel loading dose

Collaborators and Investigators

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

Sponsor

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

May 1, 2010

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

April 23, 2010

First Submitted That Met QC Criteria

May 3, 2010

First Posted (Estimate)

May 4, 2010

Study Record Updates

Last Update Posted (Estimate)

November 20, 2012

Last Update Submitted That Met QC Criteria

November 15, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13533
  • H7T-CR-TAEH (Other Identifier: Eli Lilly and Company)
  • CTRI/2010/091/000348 (Registry Identifier: India)

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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