Warfarin and Antiplatelet Therapy in Chronic Heart Failure

This study has been completed.
Sponsor:
Collaborators:
Sanofi-Synthelabo
Bristol-Myers Squibb
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00007683
First received: December 29, 2000
Last updated: June 14, 2011
Last verified: June 2011

December 29, 2000
June 14, 2011
October 1998
July 2003   (final data collection date for primary outcome measure)
acomposite of mortality, nonfatal myocardial infarction and nonfatal stroke [ Time Frame: 30 months intake; 12-42 months follow-up ] [ Designated as safety issue: No ]
The primary safety end point was major bleeding episodes, defined as bleeding episodes leading to death or disability (including loss of neurological or special senses function), requiring surgical intervention, or associated with an acute decline of hemoglobin 2gm/dl or transfusion of >1 U packed red cells or whole blood.
Not Provided
Complete list of historical versions of study NCT00007683 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Warfarin and Antiplatelet Therapy in Chronic Heart Failure
CSP #442 - Warfarin and Antiplatelet Therapy Study in Patients With Congestive Heart Failure (WATCH)

Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events).

Primary Hypothesis: The hypothesis to be tested is whether aspirin, warfarin, and clopidogrel are equally effective in the treatment of patients with symptomatic CHF and reduced ejection fraction.

Secondary Hypothesis: If one therapy proves to be superior with regard to outcomes, what is the cost of this benefit? Can subsets of patients be identified who benefit more from a specific approach to antithrombotic therapy?

Intervention: The three treatment regimens are:

  1. Open-label Warfarin titrated to an INR of 2.5-3.0;
  2. Double blind aspirin 162 mg once daily;
  3. Double blind clopidogrel 75 mg once daily.

Primary Outcomes: Any death (all causes), non-fatal stroke, non-fatal MI.

Study Abstract: Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events).

The original target sample size was 4,500 over a 3 year enrollment period with a 2 year follow-up. This sample size yielded 90% power to detect a relative difference of 20% between treatment groups. The sample size was later amended to 1,500 over a 30 month enrollment period with a 12 month follow-up. The reduced sample size yielded 85% to detect a between treatment difference of 30%. This change became effective in March 2002.

This clinical trial enrolled 1,587 patients in 142 medical centers; VA and non-VA centers in the U.S., and medical centers in the United Kingdom and Canada. Patients were randomly and equally allocated to the 3 treatments: warfarin (administered open-label), aspirin and clopidogrel (the latter two administered double-blind). The study was conducted over a 3.5 year period, with a 2.5 year enrollment phase.

Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35% on an ACE inhibitor (unless not tolerated) and a diuretic were entered. The primary end point is the composite of death from any cause, non-fatal MI, and non-fatal stroke. All-cause mortality is the secondary end point.

The WATCH design paper has been published in the Journal of Cardiac Failure. Preliminary results were presented at the meeting of the American College of Cardiology in New Orleans on March 9, 2004. There were no significant differences between the treatment groups for the primary endpoints. The paper with final results is being prepared.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Heart Failure
  • Drug: Warfarin titrated to an INR of 2.5-3.0
    anticoagulation (administered without blinding) titrated to a target INR of 2.5 to 3.0, monitored by measurements at 6 week intervals after initial titration and stabilization.
  • Drug: Aspirin
    an antiplatelet agent whose mechanism is inhibition of thromboxane, a platelet activator) administered in a double blind manner.
  • Drug: Clopidogrel 75
    (an antiplatelet agent whose mechanism is ADP inhibition) administered in a double blind manner)
  • Active Comparator: 1
    Warfarin Titrated to an INR of 2.5-3.0
    Intervention: Drug: Warfarin titrated to an INR of 2.5-3.0
  • Active Comparator: 2
    Aspirin 182 mg
    Intervention: Drug: Aspirin
  • Active Comparator: 3
    Clopidogrel 75 mg
    Intervention: Drug: Clopidogrel 75

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1587
December 2004
July 2003   (final data collection date for primary outcome measure)

Inclusion Criteria:

Inclusion Criteria:

  • Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35%, on an ACE inhibitor (unless not tolerated) and on a diuretic.

Exclusion Criteria:

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   United Kingdom
 
NCT00007683
442
Yes
Massie, Barry - Study Chair, Department of Veterans Affairs
Department of Veterans Affairs
  • Sanofi-Synthelabo
  • Bristol-Myers Squibb
Study Chair: Barry M. Massie, MD VA Medical Center, San Francisco
Department of Veterans Affairs
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP