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
  Purpose

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).


Condition Intervention Phase
Heart Failure
Drug: Warfarin titrated to an INR of 2.5-3.0
Drug: Aspirin
Drug: Clopidogrel 75
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CSP #442 - Warfarin and Antiplatelet Therapy Study in Patients With Congestive Heart Failure (WATCH)

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 1587
Study Start Date: October 1998
Study Completion Date: December 2004
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Warfarin Titrated to an INR of 2.5-3.0
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.
Active Comparator: 2
Aspirin 182 mg
Drug: Aspirin
an antiplatelet agent whose mechanism is inhibition of thromboxane, a platelet activator) administered in a double blind manner.
Active Comparator: 3
Clopidogrel 75 mg
Drug: Clopidogrel 75
(an antiplatelet agent whose mechanism is ADP inhibition) administered in a double blind manner)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00007683

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Locations
United States, Alabama
VA Medical Center, Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States, 85012
Southern Arizona VA Health Care System, Tucson
Tucson, Arizona, United States, 85723
United States, Arkansas
Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
No. Little Rock, Arkansas, United States, 72114-1706
United States, California
Rancho Los Amigos National Rehabilitation Center
Downey, California, United States, 90242
VA Central California Health Care System, Fresno
Fresno, California, United States, 93703
VA Medical Center, Loma Linda
Loma Linda, California, United States, 92357
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304-1290
VA Medical Center, San Francisco
San Francisco, California, United States, 94121
VA Greater Los Angeles HCS, Sepulveda
Sepulveda, California, United States, 91343
Cardiovascular Consultants, Walnut Creek
Walnut Creek, California, United States, 94598
VA Greater Los Angeles Healthcare System, West LA
West Los Angeles, California, United States, 90073
United States, Colorado
VA Eastern Colorado Health Care System, Denver
Denver, Colorado, United States, 80220
United States, Connecticut
Cardiology Associates of Derby, P.C.
Derby, Connecticut, United States, 06418
St. Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06120
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, United States, 06516
United States, District of Columbia
VA Medical Center, DC
Washington, District of Columbia, United States, 20422
United States, Florida
Florida Cardiovascular Research
Atlantis, Florida, United States, 33462
VA Medical Center, Bay Pines
Bay Pines, Florida, United States, 33708
North Florida/South Georgia Veterans Health System
Gainesville, Florida, United States, 32608
Watson Clinic LLP
Lakeland, Florida, United States, 33805
Brevard Cardiology
Merritt Island, Florida, United States, 32952
VA Medical Center, Miami
Miami, Florida, United States, 33125
Cardiology Consultants - Pensacola
Pensacola, Florida, United States, 32501
University Cardiology Consultants
Tamarac, Florida, United States, 33321
James A. Haley Veterans Hospital, Tampa
Tampa, Florida, United States, 33612
United States, Georgia
VA Medical Center, Augusta
Augusta, Georgia, United States, 30904
Atlanta VA Medical and Rehab Center, Decatur
Decatur, Georgia, United States, 30033
United States, Illinois
Jesse Brown VAMC (WestSide Division)
Chicago, Illinois, United States, 60612
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States, 60141-5000
Heart Care Midwest
Peoria, Illinois, United States, 61603
United States, Indiana
River Cities Cardiology
Jeffersonville, Indiana, United States, 47130
United States, Louisiana
Overton Brooks VA Medical Center, Shreveport
Shreveport, Louisiana, United States, 71101
United States, Massachusetts
Edith Nourse Rogers Memorial Veterans Hospital, Bedford
Bedford, Massachusetts, United States, 01730
VA Boston Healthcare System, Brockton Campus
Brockton, Massachusetts, United States, 02301
Bay State Medical Center
Springfield, Massachusetts, United States, 01104
United States, Michigan
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, United States, 48113
John D. Dingell VA Medical Center, Detroit
Detroit, Michigan, United States, 48201
William Beaumont Hospital
Trey, Michigan, United States, 48095
United States, Minnesota
VA Medical Center, Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Mississippi
VA Gulf Coast Veterans Health Care System, Biloxi
Biloxi, Mississippi, United States, 39531
United States, Missouri
VA Medical Center, Kansas City MO
Kansas City, Missouri, United States, 64128
VA Medical Center, St Louis
St Louis, Missouri, United States, 63106
United States, Nebraska
Lincoln Division VA Nebraska Western IA HCS
Lincoln, Nebraska, United States, 68510
United States, Nevada
VA Sierra Nevada Health Care System
Reno, Nevada, United States, 89502
United States, New York
VA Stratton Medical Center, Albany
Albany, New York, United States, 12208
VA Western New York Healthcare System at Buffalo
Buffalo, New York, United States, 14215
New York Hospital Medical Center Of Queens
Flushing, New York, United States, 11355
North Shore University Hospital
Manhasset, New York, United States, 11030
New York Harbor HCS
New York, New York, United States, 10010
VA Medical Center, Northport
Northport, New York, United States, 11768
University of Rochester Medical Center
Rochester, New York, United States, 14642
VA Medical Center, Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
Univ of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7075
VA Medical Center, Durham
Durham, North Carolina, United States, 27705
Margaret Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28739
United States, North Dakota
VA Medical Center, Fargo
Fargo, North Dakota, United States, 58102
United States, Ohio
VA Medical Center, Cincinnati
Cincinnati, Ohio, United States, 45220
VA Medical Center, Cleveland
Cleveland, Ohio, United States, 44106
Chalmers P. Wylie VAOPC
Columbus, Ohio, United States, 43203-1278
VA Medical Center, Dayton
Dayton, Ohio, United States, 45428
United States, Oklahoma
VA Medical Center, Muskogee
Muskogee, Oklahoma, United States, 74401
VA Medical Center, Oklahoma City
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
VA Medical Center, Portland
Portland, Oregon, United States, 97201
United States, Pennsylvania
VA Medical Center, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
VA Pittsburgh Health Care System
Pittsburgh, Pennsylvania, United States, 15240
United States, Rhode Island
VA Medical Center, Providence
Providence, Rhode Island, United States, 02908
United States, South Dakota
VA Black Hills Health Care System, Fort Meade
Fort Meade, South Dakota, United States, 57741
United States, Tennessee
VA Medical Center, Memphis
Memphis, Tennessee, United States, 38104
VA Medical Center
Nashville, Tennessee, United States, 37212-2637
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0553
Michael E. DeBakey VA Medical Center (152)
Houston, Texas, United States, 77030
VA South Texas Health Care System, San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
VA Salt Lake City Health Care System, Salt Lake City
Salt Lake City, Utah, United States, 84148
United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
DUCCS Research of South Boston
South Boston, Virginia, United States, 24592
United States, West Virginia
VA Medical Center, Huntington
Huntington, West Virginia, United States, 25704
VA Medical Center, Martinsburg
Martinsburg, West Virginia, United States, 25041
United States, Wisconsin
Wlliam S. Middleton Memorial Veterans Hospital, Madison
Madison, Wisconsin, United States, 53705
Canada, Alberta
Cardiology Consultants
Calgary, Alberta, Canada, T2E 7C5
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Grey Nuns Com. Hospital and Health Centre
Edmonton, Alberta, Canada, T6L 5X8
Canada, British Columbia
Alder Medical Centre
Campbell River, British Columbia, Canada, V9W 6X8
North Shore Cardiology Laboratory
North Vancouver, British Columbia, Canada, V7L 2P7
Surrey Memorial Hospital - Cardiology
Surrey, British Columbia, Canada, V3V 1Z2
Canada, Manitoba
Health Sciences Centre - Cardiology Research
Winnipeg, Manitoba, Canada, R3A 1R9
St. Boniface General Hospital
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Nova Scotia
Queen Elizabeth II HSC
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Ajax and Pickering General Hospital
Ajax, Ontario, Canada, L1S 7K8
Bramptom, Research Associates
Brampton, Ontario, Canada, L6V 1B4
Hamilton Health Sciences Corp. - General Div
Hamilton, Ontario, Canada, L8L 2X2
St. Joseph's Hospital
Hamilton, Ontario, Canada, L8P 3B6
London HSC - University Campus
London, Ontario, Canada, N6A 5A5
Credit Valley Hospital Research Associates
Mississauga, Ontario, Canada, L5M 2N1
Niagara Falls Medical Center
Niagara Falls, Ontario, Canada, L2E 7H1
Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7
Etobicoke General Hospital
Rexdale, Ontario, Canada, M9V 4B8
Cardiology Research Associates
Scarborough, Ontario, Canada, M1S 4V5
Neureka Research Inc. Willett Green Millr Cntr
Sudbury, Ontario, Canada, P3E 6B4
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
Canada, Quebec
Invascor Clinical Research Inc.
Longeuil, Quebec, Canada, J4N 1E1
Cardiology Clinic - Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Hotel-Dieu D'Artabaska
Victoriaville, Quebec, Canada, G6P 6N2
Canada, Saskatchewan
Regina General Hospital
Regina, Saskatchewan, Canada, S4P 0W5
St. Paul's Hospital
Saskatoon, Saskatchewan, Canada, S7K 0Z9
Royal University Hospital
Saskatoon, Saskatchewan, Canada, S7N 0W8
United Kingdom
Royal Victoria Hospital
Belfast, Antrim, United Kingdom, BT12 6BA
Luton and Dunstable Hospital
Luton, Beds, United Kingdom, LU4 0DZ
Selly Oak Hospital
Selly Oak, Birmingham, United Kingdom, B29 6JD
Stepping Hills Hospital
Stockport, Cheshire, United Kingdom, SK2 7JE
South Cleveland Hospital
Middlesborough, Cleveland, United Kingdom, TS4 3BW
Torbay District General
Torbay, Devon, United Kingdom, TQ2 7AA
King Geroge Hospital
Ilford, Essex, United Kingdom, IG3 8YB
Castle Hill Hospital
Cottingham, Hull, United Kingdom, HU16 5JG
Blackpool Victoria Hospital
Blackpool, Lancashire, United Kingdom, FY3 8NR
Newham General Hospital
Plaistow, London, United Kingdom, E13 8SL
Wythenshawe Hospital
Wythenshawe, Manchester, United Kingdom, M23 9LT
Northwick Park Hospital and Institue for Medical R
Harrow, Middlesex, United Kingdom, HA1 3UJ
Scunthorpe General Hospital
Scunthorpe, North Lincolnshire, United Kingdom, DN15 7BH
York District Hospital
York, North Yorkshire, United Kingdom, YO3 7HE
Royal Alexandra Hospital
Paisley, Renfrewshire, United Kingdom, PA2 9PN
Princess of Wales Hospital (Grimsby)
Grimsby, South Humberside, United Kingdom, DN33 2BA
Barnsley District General
Barnsley, South Yorkshire, United Kingdom, S75 2EP
Cardiology Research Unit Sussex House
Brighton, Sussex, United Kingdom, BN2 1ES
St. James' University Hospital
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Pontefract General Infirmary
Pontefract, West Yorshire, United Kingdom, WF8 1PL
Northern General Hospital
Sheffield, Yorkshire, United Kingdom, S5 7AU
Bridlington and District Hospital
Bridlington, United Kingdom, YO16 4QP
Derbyshire Royal Infirmary
Derby, United Kingdom, DE1 2QY
Derriford Hospital
Devon, United Kingdom, PL6 8DH
Glasgow Western Infirmary
Glasgow, United Kingdom, G12 8QQ
St. Thomas' Hospital
London, United Kingdom, SE1 7EH
Pinderfields General Hospital
Wakefield, United Kingdom, WF1 4DG
Sponsors and Collaborators
Sanofi-Synthelabo
Bristol-Myers Squibb
Investigators
Study Chair: Barry M. Massie, MD VA Medical Center, San Francisco
  More Information

Publications:
Responsible Party: Massie, Barry - Study Chair, Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00007683     History of Changes
Other Study ID Numbers: 442
Study First Received: December 29, 2000
Last Updated: June 14, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
aspirin
clopidogrel
embolic events
Left ventricular ejection fraction less than or eq
NYHA Class II, III or IV CHF
symptomatic CHF
warfarin

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Aspirin
Clopidogrel
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents

ClinicalTrials.gov processed this record on September 18, 2014