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

This study has been completed.
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
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 
Overall Participants Analyzed 
[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 ]

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
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Additional Description No text entered.

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

Serious Adverse Events
    Aspirin   Warfarin
Total, serious adverse events     
# participants affected / at risk   617/1163 (53.05%)   632/1142 (55.34%) 
Blood and lymphatic system disorders     
Blood dyscrasia †     
# participants affected / at risk   3/1163 (0.26%)   4/1142 (0.35%) 
# events   3   4 
BLOOD/BONE MARROW: Other †     
# participants affected / at risk   1/1163 (0.09%)   3/1142 (0.26%) 
# events   1   4 
Thrombocytopenia/Anemia/Leukopenia †     
# participants affected / at risk   1/1163 (0.09%)   12/1142 (1.05%) 
# events   1   12 
Hemorrhage/Bleeding †     
# participants affected / at risk   0/1163 (0.00%)   1/1142 (0.09%) 
# events   0   1 
LYMPHATICS: Other †     
# participants affected / at risk   1/1163 (0.09%)   0/1142 (0.00%) 
# events   1   0 
Peripheral edema †     
# participants affected / at risk   4/1163 (0.34%)   4/1142 (0.35%) 
# events   4   4 
Cardiac disorders     
Atrial fibrillation/Atrial flutter/Supraventricular tachycardia †     
# participants affected / at risk   56/1163 (4.82%)   35/1142 (3.06%) 
# events   67   45 
Bradycardia †     
# participants affected / at risk   6/1163 (0.52%)   6/1142 (0.53%) 
# events   6   6 
CARDIAC ARRHYTHMIA: Other †     
# participants affected / at risk   7/1163 (0.60%)   3/1142 (0.26%) 
# events   7   3 
Ventricular fibrillation †     
# participants affected / at risk   7/1163 (0.60%)   15/1142 (1.31%) 
# events   8   17 
Ventricular tachycardia †     
# participants affected / at risk   24/1163 (2.06%)   39/1142 (3.42%) 
# events   33   46 
Acute cardiac failure/CHF/Pulmonary edema †     
# participants affected / at risk   209/1163 (17.97%)   243/1142 (21.28%) 
# events   432   506 
AICD firing/discharge †     
# participants affected / at risk   16/1163 (1.38%)   20/1142 (1.75%) 
# events   21   21 
Angina/Chest pain †     
# participants affected / at risk   70/1163 (6.02%)   88/1142 (7.71%) 
# events   105   148 
CARDIAC GENERAL: Other †     
# participants affected / at risk   16/1163 (1.38%)   16/1142 (1.40%) 
# events   18   19 
Malignant hypertension †     
# participants affected / at risk   3/1163 (0.26%)   7/1142 (0.61%) 
# events   3   7 
Myocardial infarction/Acute Coronary Syndrome †     
# participants affected / at risk   48/1163 (4.13%)   50/1142 (4.38%) 
# events   60   59 
Pulmonary embolism †     
# participants affected / at risk   6/1163 (0.52%)   5/1142 (0.44%) 
# events   6   5 
Endocrine disorders     
Diabetes mellitus and its complications †     
# participants affected / at risk   26/1163 (2.24%)   22/1142 (1.93%) 
# events   35   35 
ENDOCRINE: Other †     
# participants affected / at risk   2/1163 (0.17%)   1/1142 (0.09%) 
# events   2   1 
Eye disorders     
OCULAR/VISUAL: Other †     
# participants affected / at risk   5/1163 (0.43%)   3/1142 (0.26%) 
# events   7   5 
Gastrointestinal disorders     
Gastrointestinal disturbance/Diarrhea/Jaundice/Nausea/Stomach pain/Etc. †     
# participants affected / at risk   54/1163 (4.64%)   66/1142 (5.78%) 
# events   70   82 
GASTROINTESTINAL: Other †     
# participants affected / at risk   25/1163 (2.15%)   17/1142 (1.49%) 
# events   31   18 
General disorders     
ALLERGY/IMMUNOLOGY: Other †     
# participants affected / at risk   1/1163 (0.09%)   1/1142 (0.09%) 
# events   1   1 
Laryngeal edema/Allergic reaction/Anaphylaxis/Angioedema/Rash †     
# participants affected / at risk   4/1163 (0.34%)   2/1142 (0.18%) 
# events   4   2 
CONSTITUTIONAL SYMPTOMS: Other †     
# participants affected / at risk   7/1163 (0.60%)   1/1142 (0.09%) 
# events   7   1 
Drug abuse †     
# participants affected / at risk   3/1163 (0.26%)   1/1142 (0.09%) 
# events   3   1 
OTHER: Other †     
# participants affected / at risk   19/1163 (1.63%)   32/1142 (2.80%) 
# events   23   33 
Pregnancy †     
# participants affected / at risk   0/1163 (0.00%)   1/1142 (0.09%) 
# events   0   1 
Suicide attempt/Psychiatric disorder †     
# participants affected / at risk   16/1163 (1.38%)   10/1142 (0.88%) 
# events   16   10 
PAIN: Other †     
# participants affected / at risk   14/1163 (1.20%)   13/1142 (1.14%) 
# events   15   20 
Hepatobiliary disorders     
Acute hepatic failure †     
# participants affected / at risk   3/1163 (0.26%)   3/1142 (0.26%) 
# events   3   3 
HEPATOBILIARY/PANCREAS: Other †     
# participants affected / at risk   3/1163 (0.26%)   5/1142 (0.44%) 
# events   3   7 
Infections and infestations     
Infection/Sepsis/Fever †     
# participants affected / at risk   66/1163 (5.67%)   79/1142 (6.92%) 
# events   79   97 
Metabolism and nutrition disorders     
Metabolic disturbance/Gout †     
# participants affected / at risk   14/1163 (1.20%)   16/1142 (1.40%) 
# events   15   17 
METABOLIC/LABORATORY: Other †     
# participants affected / at risk   12/1163 (1.03%)   10/1142 (0.88%) 
# events   14   11 
Musculoskeletal and connective tissue disorders     
MUSCULOSKELETAL/SOFT TISSUE: Other †     
# participants affected / at risk   39/1163 (3.35%)   29/1142 (2.54%) 
# events   43   32 
Visceral necrosis †     
# participants affected / at risk   0/1163 (0.00%)   4/1142 (0.35%) 
# events   0   4 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
MALIGNANCY: Other †     
# participants affected / at risk   22/1163 (1.89%)   20/1142 (1.75%) 
# events   24   24 
Nervous system disorders     
Convulsions/Seizures †     
# participants affected / at risk   6/1163 (0.52%)   5/1142 (0.44%) 
# events   6   10 
NEUROLOGY: Other †     
# participants affected / at risk   8/1163 (0.69%)   7/1142 (0.61%) 
# events   8   7 
Stroke or TIA †     
# participants affected / at risk   13/1163 (1.12%)   15/1142 (1.31%) 
# events   16   16 
Syncope/Pre-syncope †     
# participants affected / at risk   41/1163 (3.53%)   68/1142 (5.95%) 
# events   48   83 
Renal and urinary disorders     
Acute renal failure/Proteinuria †     
# participants affected / at risk   28/1163 (2.41%)   33/1142 (2.89%) 
# events   32   36 
RENAL/GENITOURINARY: Other †     
# participants affected / at risk   7/1163 (0.60%)   7/1142 (0.61%) 
# events   7   7 
Reproductive system and breast disorders     
SEXUAL/REPRODUCTIVE FUNCTION: Other †     
# participants affected / at risk   2/1163 (0.17%)   6/1142 (0.53%) 
# events   2   6 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure †     
# participants affected / at risk   7/1163 (0.60%)   9/1142 (0.79%) 
# events   8   9 
Pulmonary disease/Pneumonia/Bronchitis/Asthma/Breathing difficulties †     
# participants affected / at risk   87/1163 (7.48%)   79/1142 (6.92%) 
# events   133   100 
PULMONARY/UPPER RESPIRATORY: Other †     
# participants affected / at risk   7/1163 (0.60%)   3/1142 (0.26%) 
# events   7   3 
Skin and subcutaneous tissue disorders     
DERMATOLOGY/SKIN: Other †     
# participants affected / at risk   1/1163 (0.09%)   0/1142 (0.00%) 
# events   1   0 
Grade 4 dermatologic manifestations †     
# participants affected / at risk   1/1163 (0.09%)   1/1142 (0.09%) 
# events   2   1 
Surgical and medical procedures     
"Cardiac device implantation (pacemaker, defibrillator, etc.)" †     
# participants affected / at risk   123/1163 (10.58%)   109/1142 (9.54%) 
# events   133   118 
"Cardiac procedure (stent, catheterization, EP study, ablation, etc.)" †     
# participants affected / at risk   62/1163 (5.33%)   66/1142 (5.78%) 
# events   76   82 
Cardiac surgery †     
# participants affected / at risk   28/1163 (2.41%)   23/1142 (2.01%) 
# events   28   25 
Non-cardiac surgery/Diagnostic surgery †     
# participants affected / at risk   75/1163 (6.45%)   57/1142 (4.99%) 
# events   102   67 
SURGERY/INTRA-OPERATIVE INJURY: Other †     
# participants affected / at risk   4/1163 (0.34%)   8/1142 (0.70%) 
# events   4   8 
Vascular disorders     
Systemic embolism †     
# participants affected / at risk   3/1163 (0.26%)   5/1142 (0.44%) 
# events   3   5 
VASCULAR: Other †     
# participants affected / at risk   16/1163 (1.38%)   13/1142 (1.14%) 
# events   17   13 
Events were collected by systematic assessment




  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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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. J.L.P. (Seamus) Thompson
Organization: Columbia University
phone: 212-342-1252
e-mail: jlt12@columbia.edu


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


Responsible Party: Shunichi Homma, Columbia University
ClinicalTrials.gov Identifier: NCT00041938     History of Changes
Other Study ID Numbers: AAAC1093
U01NS039143-01 ( US NIH Grant/Contract Award Number )
R01NS39154
CRC
Study First Received: July 19, 2002
Results First Received: January 3, 2013
Last Updated: August 29, 2014
Health Authority: United States: Federal Government