Warfarin and Antiplatelet Therapy in Chronic Heart Failure

NCT ID: NCT00007683

Last Updated: 2011-06-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1587 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-10-31

Study Completion Date

2004-12-31

Brief Summary

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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

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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.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Warfarin Titrated to an INR of 2.5-3.0

Group Type ACTIVE_COMPARATOR

Warfarin titrated to an INR of 2.5-3.0

Intervention Type DRUG

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.

2

Aspirin 182 mg

Group Type ACTIVE_COMPARATOR

Aspirin

Intervention Type DRUG

an antiplatelet agent whose mechanism is inhibition of thromboxane, a platelet activator) administered in a double blind manner.

3

Clopidogrel 75 mg

Group Type ACTIVE_COMPARATOR

Clopidogrel 75

Intervention Type DRUG

(an antiplatelet agent whose mechanism is ADP inhibition) administered in a double blind manner)

Interventions

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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.

Intervention Type DRUG

Aspirin

an antiplatelet agent whose mechanism is inhibition of thromboxane, a platelet activator) administered in a double blind manner.

Intervention Type DRUG

Clopidogrel 75

(an antiplatelet agent whose mechanism is ADP inhibition) administered in a double blind manner)

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi-Synthelabo

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

US Department of Veterans Affairs

FED

Sponsor Role lead

Responsible Party

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Department of Veterans Affairs

Principal Investigators

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Barry M. Massie, MD

Role: STUDY_CHAIR

VA Medical Center, San Francisco

Locations

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VA Medical Center, Birmingham

Birmingham, Alabama, United States

Site Status

Carl T. Hayden VA Medical Center

Phoenix, Arizona, United States

Site Status

Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, United States

Site Status

Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock

No. Little Rock, Arkansas, United States

Site Status

Rancho Los Amigos National Rehabilitation Center

Downey, California, United States

Site Status

VA Central California Health Care System, Fresno

Fresno, California, United States

Site Status

VA Medical Center, Loma Linda

Loma Linda, California, United States

Site Status

VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

VA Medical Center, San Francisco

San Francisco, California, United States

Site Status

VA Greater Los Angeles HCS, Sepulveda

Sepulveda, California, United States

Site Status

Cardiovascular Consultants, Walnut Creek

Walnut Creek, California, United States

Site Status

VA Greater Los Angeles Healthcare System, West LA

West Los Angeles, California, United States

Site Status

VA Eastern Colorado Health Care System, Denver

Denver, Colorado, United States

Site Status

Cardiology Associates of Derby, P.C.

Derby, Connecticut, United States

Site Status

St. Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, United States

Site Status

VA Medical Center, DC

Washington D.C., District of Columbia, United States

Site Status

Florida Cardiovascular Research

Atlantis, Florida, United States

Site Status

VA Medical Center, Bay Pines

Bay Pines, Florida, United States

Site Status

North Florida/South Georgia Veterans Health System

Gainesville, Florida, United States

Site Status

Watson Clinic LLP

Lakeland, Florida, United States

Site Status

Brevard Cardiology

Merritt Island, Florida, United States

Site Status

VA Medical Center, Miami

Miami, Florida, United States

Site Status

Cardiology Consultants - Pensacola

Pensacola, Florida, United States

Site Status

University Cardiology Consultants

Tamarac, Florida, United States

Site Status

James A. Haley Veterans Hospital, Tampa

Tampa, Florida, United States

Site Status

VA Medical Center, Augusta

Augusta, Georgia, United States

Site Status

Atlanta VA Medical and Rehab Center, Decatur

Decatur, Georgia, United States

Site Status

Jesse Brown VAMC (WestSide Division)

Chicago, Illinois, United States

Site Status

Edward Hines, Jr. VA Hospital

Hines, Illinois, United States

Site Status

Heart Care Midwest

Peoria, Illinois, United States

Site Status

River Cities Cardiology

Jeffersonville, Indiana, United States

Site Status

Overton Brooks VA Medical Center, Shreveport

Shreveport, Louisiana, United States

Site Status

Edith Nourse Rogers Memorial Veterans Hospital, Bedford

Bedford, Massachusetts, United States

Site Status

VA Boston Healthcare System, Brockton Campus

Brockton, Massachusetts, United States

Site Status

Bay State Medical Center

Springfield, Massachusetts, United States

Site Status

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, United States

Site Status

John D. Dingell VA Medical Center, Detroit

Detroit, Michigan, United States

Site Status

William Beaumont Hospital

Trey, Michigan, United States

Site Status

VA Medical Center, Minneapolis

Minneapolis, Minnesota, United States

Site Status

VA Gulf Coast Veterans Health Care System, Biloxi

Biloxi, Mississippi, United States

Site Status

VA Medical Center, Kansas City MO

Kansas City, Missouri, United States

Site Status

VA Medical Center, St Louis

St Louis, Missouri, United States

Site Status

Lincoln Division VA Nebraska Western IA HCS

Lincoln, Nebraska, United States

Site Status

VA Sierra Nevada Health Care System

Reno, Nevada, United States

Site Status

VA Stratton Medical Center, Albany

Albany, New York, United States

Site Status

VA Western New York Healthcare System at Buffalo

Buffalo, New York, United States

Site Status

New York Hospital Medical Center Of Queens

Flushing, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

New York Harbor HCS

New York, New York, United States

Site Status

VA Medical Center, Northport

Northport, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

VA Medical Center, Syracuse

Syracuse, New York, United States

Site Status

Univ of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

VA Medical Center, Durham

Durham, North Carolina, United States

Site Status

Margaret Pardee Memorial Hospital

Hendersonville, North Carolina, United States

Site Status

VA Medical Center, Fargo

Fargo, North Dakota, United States

Site Status

VA Medical Center, Cincinnati

Cincinnati, Ohio, United States

Site Status

VA Medical Center, Cleveland

Cleveland, Ohio, United States

Site Status

Chalmers P. Wylie VAOPC

Columbus, Ohio, United States

Site Status

VA Medical Center, Dayton

Dayton, Ohio, United States

Site Status

VA Medical Center, Muskogee

Muskogee, Oklahoma, United States

Site Status

VA Medical Center, Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

VA Medical Center, Portland

Portland, Oregon, United States

Site Status

VA Medical Center, Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, United States

Site Status

VA Medical Center, Providence

Providence, Rhode Island, United States

Site Status

VA Black Hills Health Care System, Fort Meade

Fort Meade, South Dakota, United States

Site Status

VA Medical Center, Memphis

Memphis, Tennessee, United States

Site Status

VA Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, United States

Site Status

VA South Texas Health Care System, San Antonio

San Antonio, Texas, United States

Site Status

VA Salt Lake City Health Care System, Salt Lake City

Salt Lake City, Utah, United States

Site Status

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Site Status

DUCCS Research of South Boston

South Boston, Virginia, United States

Site Status

VA Medical Center, Huntington

Huntington, West Virginia, United States

Site Status

VA Medical Center, Martinsburg

Martinsburg, West Virginia, United States

Site Status

Wlliam S. Middleton Memorial Veterans Hospital, Madison

Madison, Wisconsin, United States

Site Status

Cardiology Consultants

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Grey Nuns Com. Hospital and Health Centre

Edmonton, Alberta, Canada

Site Status

Alder Medical Centre

Campbell River, British Columbia, Canada

Site Status

North Shore Cardiology Laboratory

North Vancouver, British Columbia, Canada

Site Status

Surrey Memorial Hospital - Cardiology

Surrey, British Columbia, Canada

Site Status

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Site Status

Health Sciences Centre - Cardiology Research

Winnipeg, Manitoba, Canada

Site Status

Queen Elizabeth II HSC

Halifax, Nova Scotia, Canada

Site Status

Ajax and Pickering General Hospital

Ajax, Ontario, Canada

Site Status

Bramptom, Research Associates

Brampton, Ontario, Canada

Site Status

Neureka Research Inc. Willett Green Millr Cntr

Greater Sudbury, Ontario, Canada

Site Status

Hamilton Health Sciences Corp. - General Div

Hamilton, Ontario, Canada

Site Status

St. Joseph's Hospital

Hamilton, Ontario, Canada

Site Status

London HSC - University Campus

London, Ontario, Canada

Site Status

Credit Valley Hospital Research Associates

Mississauga, Ontario, Canada

Site Status

Niagara Falls Medical Center

Niagara Falls, Ontario, Canada

Site Status

Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Etobicoke General Hospital

Rexdale, Ontario, Canada

Site Status

Cardiology Research Associates

Scarborough Village, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status

Invascor Clinical Research Inc.

Longeuil, Quebec, Canada

Site Status

Cardiology Clinic - Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status

Hotel-Dieu D'Artabaska

Victoriaville, Quebec, Canada

Site Status

Regina General Hospital

Regina, Saskatchewan, Canada

Site Status

St. Paul's Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Royal Victoria Hospital

Belfast, Antrim, United Kingdom

Site Status

Luton and Dunstable Hospital

Luton, Beds, United Kingdom

Site Status

Selly Oak Hospital

Selly Oak, Birmingham, United Kingdom

Site Status

Bridlington and District Hospital

Bridlington, Bridlington, United Kingdom

Site Status

Stepping Hills Hospital

Stockport, Cheshire, United Kingdom

Site Status

South Cleveland Hospital

Middlesbrough, Cleveland, United Kingdom

Site Status

Derbyshire Royal Infirmary

Derby, Derby, United Kingdom

Site Status

Derriford Hospital

Devon, Devon, United Kingdom

Site Status

Torbay District General

Torbay, Devon, United Kingdom

Site Status

King Geroge Hospital

Ilford, Essex, United Kingdom

Site Status

Glasgow Western Infirmary

Glasgow, Glasgow, United Kingdom

Site Status

Castle Hill Hospital

Cottingham, Hull, United Kingdom

Site Status

Blackpool Victoria Hospital

Blackpool, Lancashire, United Kingdom

Site Status

St. Thomas' Hospital

London, London, United Kingdom

Site Status

Newham General Hospital

Plaistow, London, United Kingdom

Site Status

Wythenshawe Hospital

Wythenshawe, Manchester, United Kingdom

Site Status

Northwick Park Hospital and Institue for Medical R

Harrow, Middlesex, United Kingdom

Site Status

Scunthorpe General Hospital

Scunthorpe, North Lincolnshire, United Kingdom

Site Status

York District Hospital

York, North Yorkshire, United Kingdom

Site Status

Royal Alexandra Hospital

Paisley, Renfrewshire, United Kingdom

Site Status

Princess of Wales Hospital (Grimsby)

Grimsby, South Humberside, United Kingdom

Site Status

Barnsley District General

Barnsley, South Yorkshire, United Kingdom

Site Status

Cardiology Research Unit Sussex House

Brighton, Sussex, United Kingdom

Site Status

Pinderfields General Hospital

Wakefield, United Kingdom, United Kingdom

Site Status

St. James' University Hospital

Leeds, West Yorkshire, United Kingdom

Site Status

Pontefract General Infirmary

Pontefract, West Yorshire, United Kingdom

Site Status

Northern General Hospital

Sheffield, Yorkshire, United Kingdom

Site Status

Countries

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United States Canada United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 15101020 (View on PubMed)

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.

Reference Type RESULT
PMID: 19289640 (View on PubMed)

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.

Reference Type RESULT
PMID: 19944357 (View on PubMed)

Other Identifiers

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442

Identifier Type: -

Identifier Source: org_study_id

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