Clinical trial NCT01115738: Clopidogrel to Prasugrel in Acute Coronary Syndrome (ACS) Patients
Official title: TRansferring From ClopIdogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome PatiEnTs: TRIPLET
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Coronary Syndrome
Keywords: Plavix, Effient
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-05-04
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation 6 Hours After Prasugrel Loading Dose (LD)
timeFrame: 6 hours after prasugrel loading dose
Secondary outcomes:
measure: Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation at Baseline, 2, 24 and 72 Hours After Prasugrel Loading Dose (LD)
timeFrame: Baseline and 2 hours and 24 hours and 72 hours after prasugrel loading dose
measure: Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hematocrit
timeFrame: Baseline, 72 hours
measure: Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hemoglobin
timeFrame: Baseline, 72 hours
measure: Percentage of Inhibition of Platelet Aggregation
timeFrame: Baseline and 2 and 6 and 24 and 72 hours after loading dose
measure: Percentage of Poor Responders
timeFrame: Baseline and 2 and 6 and 24 and 72 hours after loading dose
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline through 72 hours after prasugrel loading dose
measure: 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)
timeFrame: Baseline
measure: 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)
timeFrame: 6 hours after prasugrel loading dose
Other outcomes:
Locations:
city: Bangalore
country: India
facility: 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.
city: Hyderabaad
country: India
facility: 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.
city: New Delhi
country: India
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Diodati JG, Saucedo JF, Cardillo TE, Jakubowski JA, Henneges C, Effron MB, Lipkin FR, Walker JR, Duvvuru S, Sundseth SS, Fisher HN, Angiolillo DJ. Transferring from clopidogrel loading dose to prasugrel loading dose in acute coronary syndrome patients. High on-treatment platelet reactivity analysis of the TRIPLET trial. Thromb Haemost. 2014 Aug;112(2):311-22. doi: 10.1160/TH13-09-0747. Epub 2014 Apr 10.
citation: Diodati JG, Saucedo JF, French JK, Fung AY, Cardillo TE, Henneges C, Effron MB, Fisher HN, Angiolillo DJ. Effect on platelet reactivity from a prasugrel loading dose after a clopidogrel loading dose compared with a prasugrel loading dose alone: Transferring From Clopidogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome Patients (TRIPLET): a randomized controlled trial. Circ Cardiovasc Interv. 2013 Oct 1;6(5):567-74. doi: 10.1161/CIRCINTERVENTIONS.112.000063. Epub 2013 Sep 24.