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

This study has been completed.
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00699998
First received: June 16, 2008
Last updated: March 21, 2013
Last verified: March 2013
  Purpose

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).


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Clopidogrel
Drug: Prasugrel
Drug: Commercially-available Aspirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects With Unstable Angina/Non-ST-Elevation Myocardial Infarction Who Are Medically Managed

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With a Composite Endpoint of CV Death and MI [ Time Frame: Randomization through end of study (30-month visit) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 9326
Study Start Date: June 2008
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prasugrel
Prasugrel and Low-dose Commercially-available Aspirin
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
Active Comparator: Clopidogrel
Clopidogrel and Low-Dose Commercially-available Aspirin
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: Commercially-available Aspirin
Low-dose aspirin, oral, as prescribed by physician through end of study

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00699998

  Show 688 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Investigators
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
  More Information

Additional Information:
No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00699998     History of Changes
Other Study ID Numbers: 11058, H7T-MC-TABY(b)
Study First Received: June 16, 2008
Results First Received: March 21, 2013
Last Updated: March 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
ACS

Additional relevant MeSH terms:
Myocardial Infarction
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Aspirin
Ticlopidine
Clopidogrel
Prasugrel
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014