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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
Results First Received: March 21, 2013  
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
Condition: Acute Coronary Syndrome
Interventions: Drug: Clopidogrel
Drug: Prasugrel
Drug: Commercially-available Aspirin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Prasugrel: <75 Years of Age

Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (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) orally, once daily as maintenance dose through end of study.

Prasugrel: 75 Years of Age or Older

Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.

Clopidogrel: <75 Years of Age

Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin : Low-dose aspirin, oral, as prescribed by physician through end of study

Clopidogrel: 300 milligram (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

Clopidogrel: 75 Years of Age or Older

Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Clopidogrel: 300 milligram (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.


Participant Flow:   Overall Study
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
STARTED     3620     1043     3623     1040  
Received at Least 1 Dose of Study Drug     3590     1033     3590     1027  
COMPLETED     3421     957     3417     958  
NOT COMPLETED     199     86     206     82  
Withdrawal by Subject                 194                 83                 202                 80  
Physician Decision                 3                 2                 1                 1  
Lost to Follow-up                 2                 1                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Prasugrel: <75 Years of Age Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel : 30 milligram (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) orally, once daily as maintenance dose through end of study.
Prasugrel: 75 Years of Age or Older Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel: <75 Years of Age Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (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.
Clopidogrel: 75 Years of Age or Older Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (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.
Total Total of all reporting groups

Baseline Measures
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older     Total  
Number of Participants  
[units: participants]
  3620     1043     3623     1040     9326  
Age  
[units: years]
Mean ± Standard Deviation
  61.4  ± 8.55     80.3  ± 4.29     61.5  ± 8.38     80.3  ± 4.39     65.7  ± 11.02  
Gender  
[units: participants]
         
Female     1309     520     1290     531     3650  
Male     2311     523     2333     509     5676  
Race/Ethnicity, Customized  
[units: participants]
         
Caucasian     2362     767     2374     773     6276  
African     87     14     72     12     185  
Hispanic     321     109     346     86     862  
Asian     821     147     800     164     1932  
Other     29     6     30     5     70  
Unknown     0     0     1     0     1  
Region of Enrollment  
[units: participants]
         
Portugal     18     11     14     11     54  
Philippines     58     7     48     14     127  
Taiwan     6     6     4     9     25  
Slovakia     62     20     60     20     162  
Greece     14     8     10     11     43  
Costa Rica     5     1     2     2     10  
Thailand     30     17     36     10     93  
Ukraine     326     28     311     42     707  
Chile     28     15     33     13     89  
Italy     71     44     70     47     232  
India     513     56     508     64     1141  
France     29     22     29     19     99  
Denmark     21     7     17     10     55  
Korea, Republic of     35     7     33     7     82  
Panama     29     7     24     10     70  
Turkey     76     24     81     19     200  
Czech Republic     37     31     32     38     138  
Mexico     38     15     40     16     109  
Canada     58     14     61     13     146  
Brazil     154     27     147     34     362  
Romania     103     26     105     23     257  
Croatia     63     28     60     31     182  
Sweden     4     3     6     1     14  
United States     430     133     446     116     1125  
Serbia     42     4     40     5     91  
Spain     13     8     10     12     43  
Ireland     5     4     6     3     18  
Israel     75     33     85     21     214  
Russian Federation     128     22     135     14     299  
Colombia     40     21     45     17     123  
Switzerland     6     4     4     6     20  
Malaysia     35     7     33     9     84  
Peru     58     19     67     12     156  
Australia     13     6     15     7     41  
South Africa     27     11     27     12     77  
Netherlands     55     23     53     24     155  
Tunisia     20     3     20     4     47  
China     126     38     120     44     328  
Finland     3     3     5     2     13  
Lithuania     29     8     32     4     73  
Austria     6     6     6     5     23  
Malta     9     1     10     2     22  
United Kingdom     33     21     40     12     106  
Egypt     65     1     62     4     132  
Hungary     86     43     87     44     260  
Argentina     120     58     138     41     357  
Poland     137     59     129     68     393  
Belgium     7     7     7     8     29  
Singapore     2     5     5     1     13  
Bulgaria     216     48     209     55     528  
Germany     46     20     46     21     133  
New Zealand     10     3     10     3     26  
History of Diabetes  
[units: participants]
         
Yes     1393     363     1418     365     3539  
No     2221     678     2193     675     5767  
Unknown     6     2     12     0     20  
History of Myocardial Infarction (MI)  
[units: participants]
         
Yes     1556     426     1612     393     3987  
No     2035     603     1988     633     5259  
Unknown     29     14     23     14     80  
History of Coronary Revascularization (PCI or CABG) [1]
[units: participants]
         
Yes     1279     330     1365     299     3273  
No     2332     703     2239     734     6008  
Unknown     9     10     19     7     45  
Clinical Presentation of UA or NSTEMI [2]
[units: participants]
         
Unstable Angina     963     166     981     192     2302  
Non-ST-segment Elevation Myocardial Infarction     2453     829     2434     804     6520  
Unknown/Did not meet criteria     204     48     208     44     504  
[1] History of Coronary Revascularization due to percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
[2] Clinical Presentation of unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI)



  Outcome Measures
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1.  Primary:   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) ]

2.  Secondary:   Percentage of Participants With a Composite Endpoint of CV Death and MI   [ Time Frame: Randomization through end of study (30-month visit) ]

3.  Secondary:   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) ]

4.  Secondary:   Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke   [ Time Frame: Randomization through end of study (30-month visit) ]

5.  Secondary:   Platelet Aggregation Measures   [ Time Frame: Day 30 and 12 Months ]

6.  Secondary:   Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)   [ Time Frame: Day 30 and 6 Months ]

7.  Secondary:   Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)   [ Time Frame: Day 30 and Month 6 ]

8.  Secondary:   Genotyping Related to Drug Metabolism   [ Time Frame: Baseline ]

9.  Secondary:   Economic and Quality of Life Outcomes   [ Time Frame: Baseline and follow-up (24 months) ]
  Hide Outcome Measure 9

Measure Type Secondary
Measure Title Economic and Quality of Life Outcomes
Measure Description 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.
Time Frame Baseline and follow-up (24 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants (combined <75 years and 75 years and older) with SAQ data.

Reporting Groups
  Description
Prasugrel Prasugrel and Low-dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (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.
Clopidogrel Clopidogrel and Low-Dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (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.

Measured Values
    Prasugrel     Clopidogrel  
Number of Participants Analyzed  
[units: participants]
  1506     1506  
Economic and Quality of Life Outcomes  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline, physical limitations     67.8  ± 26.1     67.0  ± 26.5  
Baseline, angina frequency     73.6  ± 22.9     73.1  ± 23.5  
24 Months, physical limitations (n=420, 412)     75.1  ± 24.4     74.5  ± 25.7  
24 Months, angina frequency (n=420, 412)     89.7  ± 20.0     89.5  ± 19.1  


Statistical Analysis 1 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the comparison of physical limitations at baseline. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.

Statistical Analysis 2 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.72
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the comparison of angina frequency at baseline. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.

Statistical Analysis 3 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.63
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the comparison of physical limitations at 24 months. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.

Statistical Analysis 4 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.53
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the comparison of angina frequency at at 24 months. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.



10.  Secondary:   Summary of All Deaths   [ Time Frame: Randomization through end of study (30-month visit) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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