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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
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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 
Overall Participants Analyzed 
[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 
[1] History of Coronary Revascularization due to percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
Clinical Presentation of UA or NSTEMI [1] 
[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] 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 ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Measure Description 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.
Time Frame Day 30 and 6 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 who received at least 1 dose of study therapy and had baseline and post-baseline BNP measurement at Day 30 or 6 Months.

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.

Measured Values
   Prasugrel: <75 Years of Age   Prasugrel: 75 Years of Age or Older   Clopidogrel: <75 Years of Age   Clopidogrel: 75 Years of Age or Older 
Participants Analyzed 
[Units: Participants]
 859   196   840   224 
Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) 
[Units: Picograms per milliliter (pg/mL)]
Geometric Mean (Standard Error)
       
Day 30   313.494  (1.039)   1082.396  (1.093)   319.345  (1.039)   951.359  (1.092) 
6 Months (n=725, 125, 701, 174)   253.434  (1.049)   770.132  (1.135)   250.982  (1.049)   722.750  (1.130) 


Statistical Analysis 1 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] 0.631
Geometric Ratio Estimate [4] 0.982
95% Confidence Interval 0.910 to 1.059
[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 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 2 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] 0.844
Geometric Ratio Estimate [4] 1.010
95% Confidence Interval 0.916 to 1.113
[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 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 6 month comparison.

Statistical Analysis 3 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] 0.098
Geometric Ratio Estimate [4] 1.138
95% Confidence Interval 0.977 to 1.325
[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 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 4 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] 0.545
Geometric Ratio Estimate [4] 1.066
95% Confidence Interval 0.867 to 1.310
[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 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 6 month comparison.



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) ]

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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