Clinical trial NCT00007683: Warfarin and Antiplatelet Therapy in Chronic Heart Failure
Official title: CSP #442 - Warfarin and Antiplatelet Therapy Study in Patients With Congestive Heart Failure (WATCH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure
Keywords: aspirin
clopidogrel
embolic events
Left ventricular ejection fraction less than or eq
NYHA Class II, III or IV CHF
symptomatic CHF
warfarin
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Sanofi-Synthelabo
name: Bristol-Myers Squibb
First posted: 2001-01-01
Enrollment: 1587
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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 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:

Primary outcomes:
measure: acomposite of mortality, nonfatal myocardial infarction and nonfatal stroke
timeFrame: 30 months intake; 12-42 months follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: VA Medical Center, Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Carl T. Hayden VA Medical Center
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System, Tucson
state: Arizona
city: No. Little Rock
country: United States
facility: Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
state: Arkansas
city: Downey
country: United States
facility: Rancho Los Amigos National Rehabilitation Center
state: California
city: Fresno
country: United States
facility: VA Central California Health Care System, Fresno
state: California
city: Loma Linda
country: United States
facility: VA Medical Center, Loma Linda
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: San Francisco
country: United States
facility: VA Medical Center, San Francisco
state: California
city: Sepulveda
country: United States
facility: VA Greater Los Angeles HCS, Sepulveda
state: California
city: Walnut Creek
country: United States
facility: Cardiovascular Consultants, Walnut Creek
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West LA
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Health Care System, Denver
state: Colorado
city: Derby
country: United States
facility: Cardiology Associates of Derby, P.C.
state: Connecticut
city: Hartford
country: United States
facility: St. Francis Hospital and Medical Center
state: Connecticut
city: West Haven
country: United States
facility: VA Connecticut Health Care System (West Haven)
state: Connecticut
city: Washington
country: United States
facility: VA Medical Center, DC
state: District of Columbia
city: Atlantis
country: United States
facility: Florida Cardiovascular Research
state: Florida
city: Bay Pines
country: United States
facility: VA Medical Center, Bay Pines
state: Florida
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic LLP
state: Florida
city: Merritt Island
country: United States
facility: Brevard Cardiology
state: Florida
city: Miami
country: United States
facility: VA Medical Center, Miami
state: Florida
city: Pensacola
country: United States
facility: Cardiology Consultants - Pensacola
state: Florida
city: Tamarac
country: United States
facility: University Cardiology Consultants
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital, Tampa
state: Florida
city: Augusta
country: United States
facility: VA Medical Center, Augusta
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur
state: Georgia
city: Chicago
country: United States
facility: Jesse Brown VAMC (WestSide Division)
state: Illinois
city: Hines
country: United States
facility: Edward Hines, Jr. VA Hospital
state: Illinois
city: Peoria
country: United States
facility: Heart Care Midwest
state: Illinois
city: Jeffersonville
country: United States
facility: River Cities Cardiology
state: Indiana
city: Shreveport
country: United States
facility: Overton Brooks VA Medical Center, Shreveport
state: Louisiana
city: Bedford
country: United States
facility: Edith Nourse Rogers Memorial Veterans Hospital, Bedford
state: Massachusetts
city: Brockton
country: United States
facility: VA Boston Healthcare System, Brockton Campus
state: Massachusetts
city: Springfield
country: United States
facility: Bay State Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center, Detroit
state: Michigan
city: Trey
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: VA Medical Center, Minneapolis
state: Minnesota
city: Biloxi
country: United States
facility: VA Gulf Coast Veterans Health Care System, Biloxi
state: Mississippi
city: Kansas City
country: United States
facility: VA Medical Center, Kansas City MO
state: Missouri
city: St Louis
country: United States
facility: VA Medical Center, St Louis
state: Missouri
city: Lincoln
country: United States
facility: Lincoln Division VA Nebraska Western IA HCS
state: Nebraska
city: Reno
country: United States
facility: VA Sierra Nevada Health Care System
state: Nevada
city: Albany
country: United States
facility: VA Stratton Medical Center, Albany
state: New York
city: Buffalo
country: United States
facility: VA Western New York Healthcare System at Buffalo
state: New York
city: Flushing
country: United States
facility: New York Hospital Medical Center Of Queens
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: New York Harbor HCS
state: New York
city: Northport
country: United States
facility: VA Medical Center, Northport
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: VA Medical Center, Syracuse
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: VA Medical Center, Durham
state: North Carolina
city: Hendersonville
country: United States
facility: Margaret Pardee Memorial Hospital
state: North Carolina
city: Fargo
country: United States
facility: VA Medical Center, Fargo
state: North Dakota
city: Cincinnati
country: United States
facility: VA Medical Center, Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: VA Medical Center, Cleveland
state: Ohio
city: Columbus
country: United States
facility: Chalmers P. Wylie VAOPC
state: Ohio
city: Dayton
country: United States
facility: VA Medical Center, Dayton
state: Ohio
city: Muskogee
country: United States
facility: VA Medical Center, Muskogee
state: Oklahoma
city: Oklahoma City
country: United States
facility: VA Medical Center, Oklahoma City
state: Oklahoma
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
city: Philadelphia
country: United States
facility: VA Medical Center, Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Health Care System
state: Pennsylvania
city: Providence
country: United States
facility: VA Medical Center, Providence
state: Rhode Island
city: Fort Meade
country: United States
facility: VA Black Hills Health Care System, Fort Meade
state: South Dakota
city: Memphis
country: United States
facility: VA Medical Center, Memphis
state: Tennessee
city: Nashville
country: United States
facility: VA Medical Center
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center (152)
state: Texas
city: San Antonio
country: United States
facility: VA South Texas Health Care System, San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City
state: Utah
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
city: South Boston
country: United States
facility: DUCCS Research of South Boston
state: Virginia
city: Huntington
country: United States
facility: VA Medical Center, Huntington
state: West Virginia
city: Martinsburg
country: United States
facility: VA Medical Center, Martinsburg
state: West Virginia
city: Madison
country: United States
facility: Wlliam S. Middleton Memorial Veterans Hospital, Madison
state: Wisconsin
city: Calgary
country: Canada
facility: Cardiology Consultants
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Com. Hospital and Health Centre
state: Alberta
city: Campbell River
country: Canada
facility: Alder Medical Centre
state: British Columbia
city: North Vancouver
country: Canada
facility: North Shore Cardiology Laboratory
state: British Columbia
city: Surrey
country: Canada
facility: Surrey Memorial Hospital - Cardiology
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre - Cardiology Research
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II HSC
state: Nova Scotia
city: Ajax
country: Canada
facility: Ajax and Pickering General Hospital
state: Ontario
city: Brampton
country: Canada
facility: Bramptom, Research Associates
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corp. - General Div
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Hospital
state: Ontario
city: London
country: Canada
facility: London HSC - University Campus
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital Research Associates
state: Ontario
city: Niagara Falls
country: Canada
facility: Niagara Falls Medical Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Rexdale
country: Canada
facility: Etobicoke General Hospital
state: Ontario
city: Scarborough
country: Canada
facility: Cardiology Research Associates
state: Ontario
city: Sudbury
country: Canada
facility: Neureka Research Inc. Willett Green Millr Cntr
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Longeuil
country: Canada
facility: Invascor Clinical Research Inc.
state: Quebec
city: Montreal
country: Canada
facility: Cardiology Clinic - Maisonneuve-Rosemont
state: Quebec
city: Victoriaville
country: Canada
facility: Hotel-Dieu D'Artabaska
state: Quebec
city: Regina
country: Canada
facility: Regina General Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: St. Paul's Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
state: Antrim
city: Luton
country: United Kingdom
facility: Luton and Dunstable Hospital
state: Beds
city: Selly Oak
country: United Kingdom
facility: Selly Oak Hospital
state: Birmingham
city: Stockport
country: United Kingdom
facility: Stepping Hills Hospital
state: Cheshire
city: Middlesborough
country: United Kingdom
facility: South Cleveland Hospital
state: Cleveland
city: Torbay
country: United Kingdom
facility: Torbay District General
state: Devon
city: Ilford
country: United Kingdom
facility: King Geroge Hospital
state: Essex
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: Hull
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: Lancashire
city: Plaistow
country: United Kingdom
facility: Newham General Hospital
state: London
city: Wythenshawe
country: United Kingdom
facility: Wythenshawe Hospital
state: Manchester
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital and Institue for Medical R
state: Middlesex
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: North Lincolnshire
city: York
country: United Kingdom
facility: York District Hospital
state: North Yorkshire
city: Paisley
country: United Kingdom
facility: Royal Alexandra Hospital
state: Renfrewshire
city: Grimsby
country: United Kingdom
facility: Princess of Wales Hospital (Grimsby)
state: South Humberside
city: Barnsley
country: United Kingdom
facility: Barnsley District General
state: South Yorkshire
city: Brighton
country: United Kingdom
facility: Cardiology Research Unit Sussex House
state: Sussex
city: Leeds
country: United Kingdom
facility: St. James' University Hospital
state: West Yorkshire
city: Pontefract
country: United Kingdom
facility: Pontefract General Infirmary
state: West Yorshire
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
state: Yorkshire
city: Bridlington
country: United Kingdom
facility: Bridlington and District Hospital
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
city: Devon
country: United Kingdom
facility: Derriford Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Western Infirmary
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital
Study officials:
affiliation: VA Medical Center, San Francisco
name: Barry M. Massie, MD
role: STUDY_CHAIR
References:
citation: Massie BM, Krol WF, Ammon SE, Armstrong PW, Cleland JG, Collins JF, Ezekowitz M, Jafri SM, O'Connor CM, Packer M, Schulman KA, Teo K, Warren S. The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics. J Card Fail. 2004 Apr;10(2):101-12. doi: 10.1016/j.cardfail.2004.02.006.
citation: Massie BM, Collins JF, Ammon SE, Armstrong PW, Cleland JG, Ezekowitz M, Jafri SM, Krol WF, O'Connor CM, Schulman KA, Teo K, Warren SR; WATCH Trial Investigators. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation. 2009 Mar 31;119(12):1616-24. doi: 10.1161/CIRCULATIONAHA.108.801753. Epub 2009 Mar 16.
citation: Patterson ME, Grant WC, Glickman SW, Massie BM, Ammon SE, Armstrong PW, Cleland JG, Collins JF, Teo KK, Schulman KA, Reed SD. Resource use and costs of treatment with anticoagulation and antiplatelet agents: results of the WATCH trial economic evaluation. J Card Fail. 2009 Dec;15(10):819-27. doi: 10.1016/j.cardfail.2009.07.004. Epub 2009 Aug 21.