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Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Shunichi Homma, Columbia University
ClinicalTrials.gov Identifier:
NCT00041938
First received: July 19, 2002
Last updated: August 29, 2014
Last verified: August 2014
Results First Received: January 3, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Heart Disease
Stroke
Ischemic Heart Disease
Myocardial Infarction
Interventions: Drug: aspirin
Drug: Warfarin

  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
Recruited 2305 patients at 176 sites in 11 countries, between 10/1/2002 and 1/31/2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Intent-to-treat trial - all randomized patients followed and analyzed.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : International Normalized Ratio (INR) 2.5-3.0; target INR 2.75

Participant Flow:   Overall Study
    Aspirin     Warfarin  
STARTED     1163     1142  
Completed Follow-up     761     745  
Primary Endpoint     320     302  
Only Vital Status Known     44     46  
Lost to Follow-up     18     17  
Withdrew Consent     20     14  
COMPLETED     1125     1111  
NOT COMPLETED     38     31  



  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
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75
Total Total of all reporting groups

Baseline Measures
    Aspirin     Warfarin     Total  
Number of Participants  
[units: participants]
  1163     1142     2305  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     732     706     1438  
>=65 years     431     436     867  
Age  
[units: years]
Mean ± Standard Deviation
  61  ± 11.1     61  ± 11.6     61  ± 11.3  
Gender, Customized  
[units: participants]
     
Male     936     904     1840  
Female     224     236     460  
Unknown     3     2     5  
Region of Enrollment  
[units: participants]
     
North America     546     573     1119  
Europe     567     527     1094  
Argentina     50     42     92  



  Outcome Measures
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1.  Primary:   Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death   [ Time Frame: From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years ]
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Measure Type Primary
Measure Title Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
Measure Description The time, in years, from randomization to the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years  
Safety Issue Yes  

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.
Intent-to-treat analysis: all enrolled patients were analyzed.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death  
[units: events per 100 patient-years]
  7.93     7.47  


Statistical Analysis 1 for Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.40
Hazard Ratio (HR) [4] 0.93
95% Confidence Interval ( 0.79 to 1.10 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary null hypothesis: time to first event in the composite primary endpoint does not differ significantly between warfarin and aspirin. The original target sample size was 2860, providing 89% power for a log-rank test with two-sided alpha .05, assuming a hazard rate reduction of 17.82% in either group compared with the other, after adjustment for use of beta-blockers and allowance for discontinuation of therapy, dropout, and crossover. The final sample of 2305 patients yielded 69% power.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox models stratified by site, New York Heart Association class (I vs. II-IV), and status w/ respect to recent stroke or Transient Ischemic Attack.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The primary null hypotheses was tested at two-tailed alpha=0.05. A Haybittle-Peto interim monitoring procedure was performed with stopping boundaries for the interim analyses corresponding to a nominal two-tailed P value of 0.001.
[4] Other relevant estimation information:
  Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.



2.  Secondary:   Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.   [ Time Frame: From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. ]

3.  Other Pre-specified:   Event Rate Per 100 Patient-years for Ischemic Stroke   [ Time Frame: From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years ]

4.  Other Pre-specified:   Event Rate Per 100 Patient-years for Intracerebral Hemorrhage   [ Time Frame: From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years ]

5.  Other Pre-specified:   Event Rate Per 100 Patient-years for Death   [ Time Frame: From date of randomization to date of death component of primary composite outcome, up to 6 years ]

6.  Other Pre-specified:   Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years ]

7.  Other Pre-specified:   Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.   [ Time Frame: From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years ]

8.  Other Pre-specified:   Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years ]

9.  Other Pre-specified:   Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years ]

10.  Other Pre-specified:   Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of death component of secondary composite outcome, up to 6 years ]

11.  Other Pre-specified:   Rate Per 100 Patient Years of Major Hemorrhage   [ Time Frame: From date of randomization until end of scheduled follow-up, up to 6 years ]

12.  Other Pre-specified:   Rate Per 100 Patient-years of Minor Hemorrhage.   [ Time Frame: From date of randomization until the end of scheduled follow-up, up to 6 years ]


  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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