Clopidogrel to Prasugrel in Acute Coronary Syndrome (ACS) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01115738
First received: April 23, 2010
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Prasugrel
Drug: Clopidogrel
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: TRansferring From ClopIdogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome PatiEnTs: TRIPLET

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation 6 Hours After Prasugrel Loading Dose (LD) [ Time Frame: 6 hours after prasugrel loading dose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hematocrit [ Time Frame: Baseline, 72 hours ] [ Designated as safety issue: Yes ]
  • Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hemoglobin [ Time Frame: Baseline, 72 hours ] [ Designated as safety issue: Yes ]
  • Percentage of Inhibition of Platelet Aggregation [ Time Frame: Baseline and 2 and 6 and 24 and 72 hours after loading dose ] [ Designated as safety issue: No ]
    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.

  • Percentage of Poor Responders [ Time Frame: Baseline and 2 and 6 and 24 and 72 hours after loading dose ] [ Designated as safety issue: No ]
    Poor responders are those who had P2Y12 Reaction Units (PRU)≥ 240.

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline through 72 hours after prasugrel loading dose ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 282
Study Start Date: May 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: LY640315
Drug: Clopidogrel
Loading dose administered once orally.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01115738

Locations
India
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.
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
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01115738     History of Changes
Other Study ID Numbers: 13533, H7T-CR-TAEH, CTRI/2010/091/000348
Study First Received: April 23, 2010
Results First Received: September 25, 2012
Last Updated: November 15, 2012
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: Ministry of Health
Canada: Health Canada
India: Ministry of Science and Technology
Mexico: Federal Commission for Sanitary Risks Protection
Turkey: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Plavix, Effient

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Ticlopidine
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 29, 2014