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A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00699998
Recruitment Status : Completed
First Posted : June 18, 2008
Results First Posted : May 7, 2013
Last Update Posted : May 7, 2013
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE June 16, 2008
First Posted Date  ICMJE June 18, 2008
Results First Submitted Date  ICMJE March 21, 2013
Results First Posted Date  ICMJE May 7, 2013
Last Update Posted Date May 7, 2013
Study Start Date  ICMJE June 2008
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2013)		 Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke [ Time Frame: Randomization through end of study (30-month visit) ]
The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Original Primary Outcome Measures  ICMJE
 (submitted: June 16, 2008)		 Reduction in risk of the composite endpoint of first occurrence of CV death, MI, or stroke. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2013)
  • Percentage of Participants With a Composite Endpoint of CV Death and MI [ Time Frame: Randomization through end of study (30-month visit) ]
    The percentage of participants is the total number of participants experiencing a CV death or nonfatal MI divided by number of participants in the treatment arm. Endpoint events were adjudicated by the Clinical Endpoint Committee.
  • Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA) [ Time Frame: Randomization through end of study (30-month visit) ]
    The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, nonfatal stroke or re-hospitalization for a recurrent UA divided by number of participants in the treatment arm. Endpoints events were adjudicated by the Clinical Endpoint Committee.
  • Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke [ Time Frame: Randomization through end of study (30-month visit) ]
    The percentage of participants is the total number of participants experiencing an all-cause death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm. Endpoint events were adjudicated by the Clinical Endpoint Committee.
  • Platelet Aggregation Measures [ Time Frame: Day 30 and 12 Months ]
    Platelet aggregation was measured by as measured by Accumetrics Verify Now™ P2Y12. Results were reported in P2Y12 Reaction Units (PRU). PRU represents the rate and extent of adenosine (ADP)-stimulated platelet aggregation. Lower values indicate greater P2Y12 platelet inhibition and lower platelet activity and aggregation. ANCOVA Model was used and values were corrected for treatment + baseline value + clopidogrel status at randomization.
  • Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) [ Time Frame: Day 30 and 6 Months ]
    Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart in response to hemodynamic stress and is a biomarker associated with increased CV risk. Results are presented as geometric least squares means (Geometric LS means). Geometric LS means were adjusted for treatment + baseline value + clopidogrel status at randomization.
  • Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) [ Time Frame: Day 30 and Month 6 ]
    C-Reactive Protein (CRP) is a biomarker associated with inflammation and increased CV risk. Results are presented as geometric least squares means (Geometric LS means). Geometric LS means were adjusted for treatment + baseline value + clopidogrel status at randomization.
  • Genotyping Related to Drug Metabolism [ Time Frame: Baseline ]
    Variation in the genes encoding the cytochrome P450 (CYP) enzymes (CYP2C19) can reduce the ability to metabolize clopidogrel and a reduced platelet response and have been associated with increased rates of CV events including CV death. Participants were classified as extensive metabolizers (EM); reduced metabolizers (RM); or unknown (UNK) metabolizers based on their CYP2C19 genotype. Possible extensive metabolizer (EM) phenotypes include EM=extensive metabolizer, UM=ultra-rapid metabolizer, and EM (non-UM) that are not UM. Possible reduced metabolizer (RM) phenotypes include IM=intermediate metabolizer and PM=poor metabolizer. Genotypes associated with each predicted phenotype are presented; predicted phenotype is presented first followed by the genotype. Percentage=(number of participants with the predicted phenotype and genotype divided by the total number of participants per arm) multiplied by 100.
  • Economic and Quality of Life Outcomes [ Time Frame: Baseline and follow-up (24 months) ]
    Seattle Angina Questionnaire (SAQ) is a validated, disease-specific questionnaire containing 11 questions (Q) yielding 5 summary scales related to angina: physical limitations, angina stability, angina frequency, treatment satisfaction and disease perception. In this study only angina frequency and the physical limitations scales were assessed. Anginal Frequency was assessed using Q3 and Q4 which consists of a Likert scale ranging from 1 to 6 (higher values equals better quality of life) to assess how often a patient is having symptoms now. Physical limitations was assessed using Q1 which contains 9 items each assessed via Likert scale ranging from 1 to 6 (higher values equals better quality of life) to assess how much a participant's condition is hampering their ability to do what they want to do. Scale scores are transformed to a 0-100 by subtracting the lowest possible score, dividing by the range of the scale, and multiplying by 100. Higher values equal better quality of life.
  • Summary of All Deaths [ Time Frame: Randomization through end of study (30-month visit) ]
    All deaths, regardless of possible relatedness, with the exception of 1 event, were adjudicated by the Clinical Endpoint Committee (CEC) and are reported in this table. The 1 event which was not adjudicated was a result of the revocation of consent by the participant prior to their death. Deaths possibly related to study drug in the opinion of the investigator are also contained in the Serious Adverse Event (SAE) module.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2008)
  • Risk of the composite endpoint of first occurence of CV death and MI. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ]
  • Risk of the composite endpoint of first occurrence CV death, MI, stroke, or re-hospitalization for recurrent UA. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ]
  • Risk of the composite endpoint of first occurrence of all-cause death, MI, or stroke. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ]
  • Platelet aggregation measures. [ Time Frame: Baseline and at various timepoints during study treatment. ]
  • Biomarker measurements of inflammation/hemodynamic stress. [ Time Frame: Baseline and at various timepoints during study treatment. ]
  • Genotyping related to drug metabolism. [ Time Frame: Baseline ]
  • Economic and Quality of Life Outcomes. [ Time Frame: Baseline, follow-up, and discontinuation from study. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects
Official Title  ICMJE A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects With Unstable Angina/Non-ST-Elevation Myocardial Infarction Who Are Medically Managed
Brief Summary This study will evaluate the relative efficacy and safety of prasugrel and clopidogrel in a medically managed Unstable Angina/Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) acute coronary syndrome (ACS) population (that is, patients who are not managed with acute coronary revascularization).
Detailed Description Based upon the significant number of subjects with UA/NSTEMI ACS who are managed medically and their high risk for future cardiovascular events, further exploration of novel treatment strategies for this population, who are under-represented in large clinical trials, is warranted. Potential subjects will be those with a recent UA/NSTEMI event who are to be medically managed. Eligibility for this study will be determined by both the timing of the medical management decision and by prior commercial clopidogrel treatment at the time of randomization. The TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) Study will assess the efficacy and safety of prasugrel and aspirin compared to the current standard of care, clopidogrel and aspirin, for long-term treatment of medically managed UA/NSTEMI ACS subjects.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Acute Coronary Syndrome
Intervention  ICMJE
  • Drug: Clopidogrel
    300 milligrams (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study
  • Drug: Prasugrel
    30 milligrams (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight and age), oral, once daily as maintenance dose through end of study
    Other Names:
    • LY640315
    • Effient
    • Efient
    • CS-747
  • Drug: Commercially-available Aspirin
    Low-dose aspirin, oral, as prescribed by physician through end of study
Study Arms  ICMJE
  • Experimental: Prasugrel
    Prasugrel and Low-dose Commercially-available Aspirin
    Interventions:
    • Drug: Prasugrel
    • Drug: Commercially-available Aspirin
  • Active Comparator: Clopidogrel
    Clopidogrel and Low-Dose Commercially-available Aspirin
    Interventions:
    • Drug: Clopidogrel
    • Drug: Commercially-available Aspirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2013)		 9326
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2008)		 10300
Actual Study Completion Date  ICMJE April 2012
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Have had a Unstable Angina/Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) index event within 10 days prior to randomization
  • Had a medical management strategy decision made with reasonable certainty that neither percutaneous coronary intervention (PCI) nor coronary artery bypass graft (CABG) is planned for treatment of the index event
  • Had at least 1 of 4 specified high-risk features at the time of the UA/NSTEMI event

Key Exclusion Criteria:

  • Decision for medical management greater than 72 hours after onset of index event without commercial clopidogrel treatment within 72 hours following onset of the index event.
  • Insignificant coronary artery disease (CAD) on coronary angiography if performed for Index Event (absence of greater than or equal to 30% stenosis in at least one native vessel)
  • Previous or planned PCI or CABG as treatment for the index event
  • PCI/CABG within previous 30 days
  • ST-segment elevation myocardial infarction (STEMI) as the index event
  • Cardiogenic shock, Refractory ventricular arrhythmias, New York Heart Association (NYHA) Class IV congestive heart failure (CHF) within the previous 24 hours
  • History of ischemic or hemorrhagic stroke, transient ischemic attack (TIA), Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • History of spontaneous gastrointestinal (GI) or non-GI bleeding requiring hospitalization for treatment, unless definitive treatment has occurred and there is low likelihood of recurrence
  • Hemodialysis or peritoneal dialysis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Costa Rica,   Croatia,   Czech Republic,   Denmark,   Egypt,   Finland,   France,   Germany,   Greece,   Hungary,   India,   Ireland,   Israel,   Italy,   Korea, Republic of,   Lithuania,   Malaysia,   Malta,   Mexico,   Netherlands,   New Zealand,   Panama,   Peru,   Philippines,   Poland,   Portugal,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Tunisia,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Saudi Arabia
 
Administrative Information
NCT Number  ICMJE NCT00699998
Other Study ID Numbers  ICMJE 11058
H7T-MC-TABY(b) ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Eli Lilly and Company
Original Responsible Party Chief Medical Officer, Eli Lilly
Current Study Sponsor  ICMJE Eli Lilly and Company
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Daiichi Sankyo Co., Ltd.
  • Duke Clinical Research Institute
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP