Clinical Trial: Are Aspirin, Warfarin, and Clopidogrel Equally Effective in the Treatment of Patients With Symptomatic CHF and Reduced Ejection Fraction?

This study has been completed.

Sponsors and Collaborators: Department of Veterans Affairs
Canadian Regional Coordinating Center
UK Regional Coordinating Center
Economic Analysis Lab
Echo Core Lab
Sanofi-Synthelabo
Bristol-Myers Squibb
Dupont Pharmaceuticals
Information provided by: Department of Veterans Affairs

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 Treatment or Intervention Phase
NYHA Class II, III or IV CHF
Left ventricular ejection fraction less than or equal to 35%
 Drug: Warfarin titrated to an INR of 2.5-3.0
 Drug: Aspirin
 Drug: Clopidogrel
Phase III

MedlinePlus consumer health information 

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study

Official Title: CSP #442 - Warfarin and Antiplatelet Therapy in Chronic Heart Failure

Further Study Details: 

Expected Total Enrollment:  1587

Study start: October 1998;  Study completion: June 2003

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: a. Open-label Warfarin titrated to an INR of 2.5-3.0; b. Double blind aspirin 162 mg once daily; c. Double blind clopidogrel 75 mg once daily.

Primary Outcomes: Any of 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).

This clinical trial will enroll 1,500 patients in approximately 150-160 medical centers; VA and non-VA centers in the U.S., and medical centers in the United Kingdom and Canada. Patients will be randomly and equally allocated to the 3 treatments: warfarin (administered open-label), aspirin and clopidogrel (the latter two administered double-blind). The study will be 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 will be entered. The primary end point will be the composite of death from any cause, non-fatal MI, and non-fatal stroke. The study has 85% power to detect a 30% difference between treatment groups. All-cause mortality will be the secondary end point.

* Value of donated study drugs, Clopidogrel and Aspirin (Sanofi): $10,158,750. ** Value of donated study drug, Warfarin (Dupont): $1,080,000.

Eligibility

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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.

Location Information


Alabama
      VAMC - Birmingham, AL, Birmingham,  Alabama,  35233,  United States

Arizona
      VAMC - Phoenix, AZ, Phoenix,  Arizona,  85012,  United States

      VAMC - Tucson, AZ, Tucson,  Arizona,  85723,  United States

Arkansas
      VAMC - Little Rock, AR, Little Rock,  Arkansas,  72205,  United States

California
      VAMC - Fresno, CA, Fresno,  California,  93703,  United States

      VAMC - Loma Linda, CA, Loma Linda,  California,  92354,  United States

      Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States

      Vamc - West Los Angeles, Ca, Los Angeles,  California,  90073,  United States

      VAMC - San Francisco, CA, San Francisco,  California,  94121,  United States

      Cardiovascular Consultants, Walnut Creek, Ca, Walnut Creek,  California,  94598,  United States

      Heart Center of Los Angeles, Los Angeles, Ca, Los Angeles,  California,  90048,  United States

      Rancho Los Amigos National Rehabilitation Center, Downey,  California,  90242,  United States

      VAMC Palo Alto, Palo Alto,  California,  94304,  United States

Colorado
      VAMC - Denver, CO, Denver,  Colorado,  80220,  United States

Connecticut
      VAMC - West Haven, CT, West Haven,  Connecticut,  06516,  United States

      St. Francis Hospital and Medical Center, Hartford,  Connecticut,  06120,  United States

      Cardiology Associates of Derby, P.C., Derby,  Connecticut,  06418,  United States

District of Columbia
      Washington DC VAMC, Washington,  District of Columbia,  20422,  United States

Florida
      VAMC - Bay Pines, FL, Bay Pines,  Florida,  33744,  United States

      Cardiology Assoc. of Gainesville, Gainesville,  Florida,  32601,  United States

      Florida Cardiovascular Research, Atlantis,  Florida,  33462,  United States

      University Cardiology Consultants, Tamarac,  Florida,  33321,  United States

      Brevard Cardiology, Merritt Island,  Florida,  32952,  United States

      Cardiology Consultants - Pensacola, Pensacola,  Florida,  32501,  United States

      VAMC - Miami, FL, Miami,  Florida,  33125,  United States

      VAMC - Tampa, FL, Tampa,  Florida,  33612,  United States

      Watson Clinic LLP, Lakeland,  Florida,  33805,  United States

Georgia
      Augusta Cardiology Clinic, PC, Augusta,  Georgia,  30901,  United States

      Emory Univ. School of Med., Atlanta, Ga, Atlanta,  Georgia,  30303,  United States

Illinois
      Heart Care Midwest, Peoria,  Illinois,  61603,  United States

      VAMC - Hines, IL, Hines,  Illinois,  60141,  United States

      Northwestern University, Chicago,  Illinois,  60611-2450,  United States

Indiana
      River Cities Cardiology, Jeffersonville,  Indiana,  47130,  United States

Louisiana
      Cardiac Centers of Louisiana, L.L.C., Shreveport,  Louisiana,  71103,  United States

Massachusetts
      Bay State Medical Center, Springfield,  Massachusetts,  01104,  United States

      VAMC - West Roxbury, MA, West Roxbury,  Massachusetts,  02132,  United States

Michigan
      William Beaumont Hospital, Troy,  Michigan,  48095,  United States

      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States

      VAMC - Ann Arbor, MI, Ann Arbor,  Michigan,  48105,  United States

Minnesota
      VAMC - Minneapolis, MN, Minneapolis,  Minnesota,  55417,  United States

Mississippi
      VAMC Biloxi, Biloxi,  Mississippi,  39531,  United States

Missouri
      Mercy Cardiology Clinic, Inc., St. Louis,  Missouri,  63141,  United States

      VAMC - Kansas City, MO, Kansas City,  Missouri,  64128,  United States

      Washington University, St. Louis,  Missouri,  63110,  United States

Nebraska
      Nebraska Heart Institute, Lincoln,  Nebraska,  68506,  United States

Nevada
      VAMC - Reno, NV, Reno,  Nevada,  89520,  United States

New York
      VAMC - Albany, NY, Albany,  New York,  12208,  United States

      VAMC - Northport, NY, Northport,  New York,  11768,  United States

      Buffalo General Hospital, Buffalo,  New York,  14203,  United States

      Columbia University, New York,  New York,  10032,  United States

      North Shore University Hospital, Manhasset,  New York,  11030,  United States

      University of Rochester Medical Center, Rochester,  New York,  14642,  United States

      VAMC - Syracuse, NY, Syracuse,  New York,  13210,  United States

      New York Hospital Medical Center of Queens, Flushing,  New York,  11355,  United States

North Carolina
      Univ of North Carolina at Chapel Hill, Chapel Hill,  North Carolina,  27599-7075,  United States

      Duke University Medical Center, Durham,  North Carolina,  27710-0001,  United States

      VAMC - Durham, NC, Durham,  North Carolina,  27705,  United States

      Margaret Pardee Memorial Hospital, Hendersonville,  North Carolina,  28739,  United States

North Dakota
      VAMC - Fargo, ND, Fargo,  North Dakota,  58102,  United States

Ohio
      VAMC - Dayton, OH, Dayton,  Ohio,  45428,  United States

      Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States

      VAMC - Cincinnati, Cincinnati,  Ohio,  45220,  United States

      MetroHealth Medical Center, Cleveland,  Ohio,  44109-1998,  United States

      University Hospitals of Cleveland, Cleveland,  Ohio,  44106-5038,  United States

      Vamc - Cleveland, Oh, Cleveland,  Ohio,  44106,  United States

      Ohio State University, Columbus,  Ohio,  43210,  United States

Oklahoma
      VAMC - Muskogee, OK, Muskogee,  Oklahoma,  74401,  United States

      VAMC - Oklahoma City, OK, Oklahoma City,  Oklahoma,  73104,  United States

Oregon
      VAMC - Portland, OR, Portland,  Oregon,  97201,  United States

Pennsylvania
      Hospital of the University of PA, Philadelphia,  Pennsylvania,  19104,  United States

      Albert Einstein Med Center-PA Cardiology Group, Philadelphia,  Pennsylvania,  19141,  United States

      VAMC - Pittsburgh, PA, Pittsburgh,  Pennsylvania,  15240,  United States

Rhode Island
      VAMC - Providence, RI, Providence,  Rhode Island,  02908,  United States

South Dakota
      Vamc - Black Hills, Ft Meade Sd, Fort Meade,  South Dakota,  57741,  United States

Tennessee
      Nashville VAMC, Nashville,  Tennessee,  37212-2637,  United States

      VAMC - Memphis, TN, Memphis,  Tennessee,  38104,  United States

Texas
      VAMC - Houston, TX, Houston,  Texas,  77030,  United States

      VAMC - San Antonio, TX, San Antonio,  Texas,  78229,  United States

      University of Texas Medical Branch, Galveston,  Texas,  77555-0553,  United States

Utah
      VAMC - Salt Lake City, UT, Salt Lake City,  Utah,  84148,  United States

      Lds Hospital Cardiology, Salt Lake City,  Utah,  84143,  United States

Virginia
      VAMC - Richmond, VA, Richmond,  Virginia,  23249,  United States

      DUCCS Research of South Boston, South Boston,  Virginia,  24592,  United States

West Virginia
      VAMC - Huntington, WV, Huntington,  West Virginia,  25704,  United States

      VAMC - Martinsburg WV, Martinsburg,  West Virginia,  25401,  United States

Wisconsin
      VAMC - Madison, WI, Madison,  Wisconsin,  53705,  United States

Canada, Alberta
      Cardiology Consultants, Calgary,  Alberta,  T2E 7C5,  Canada

      University of Alberta Hospital, Edmonton,  Alberta,  T6G 2B7,  Canada

      Grey Nuns Com. Hospital and Health Centre, Edmonton,  Alberta,  T6L 5X8,  Canada

Canada, British Columbia
      Alder Medical Centre, Campbell River,  British Columbia,  V9W 6X8,  Canada

      North Shore Cardiology Laboratory, North Vancouver,  British Columbia,  V7L 2P7,  Canada

      Surrey Memorial Hospital - Cardiology, Surrey,  British Columbia,  V3V 1Z2,  Canada

Canada, Manitoba
      Health Sciences Centre - Cardiology Research, Winnipeg,  Manitoba,  R3A 1R9,  Canada

      St. Boniface General Hospital, Winnipeg,  Manitoba,  R2H 2A6,  Canada

Canada, Nova Scotia
      Queen Elizabeth II HSC, Halifax,  Nova Scotia,  B3H 3A7,  Canada

Canada, Ontario
      Bramptom, Research Associates, Brampton,  Ontario,  L6V 1B4,  Canada

      St. Joseph's Hospital, Hamilton,  Ontario,  L8P 3B6,  Canada

      Neureka Research Inc. Willett Green Millr Cntr, Sudbury,  Ontario,  P3E 6B4,  Canada

      Ottawa Heart Institute, Ottawa,  Ontario,  K1Y 4W7,  Canada

      Niagara Falls Medical Center, Niagara Falls,  Ontario,  L2E 7H1,  Canada

      Toronto Western Hospital, Toronto,  Ontario,  M5T 2S8,  Canada

      London HSC - University Campus, London,  Ontario,  N6A 5A5,  Canada

      Etobicoke General Hospital, Rexdale,  Ontario,  M9V 4B8,  Canada

      St. Michael's Hospital, Toronto,  Ontario,  M5B 1W8,  Canada

      Ajax and Pickering General Hospital, Ajax,  Ontario,  L1S 7K8,  Canada

      Hamilton Health Sciences Corp. - General Div, Hamilton,  Ontario,  L8L 2X2,  Canada

      Cardiology Research Associates, Scarborough,  Ontario,  M1S 4V5,  Canada

      Credit Valley Hospital Research Associates, Mississauga,  Ontario,  L5M 2N1,  Canada

Canada, Quebec
      Invascor Clinical Research Inc., Longueuil,  Quebec,  J4N 1E1,  Canada

      Cardiology Clinic - Maisonneuve-Rosemont, Montreal,  Quebec,  H1T 2M4,  Canada

      Hotel-Dieu D'Artabaska, Quebec, Qu, Victoriaville,  Quebec,  G6P 6N2,  Canada

Canada, Saskatchewan
      St. Paul's Hospital, Saskatoon,  Saskatchewan,  S7K 0Z9,  Canada

      Regina General Hospital, Regina,  Saskatchewan,  S4P 0W5,  Canada

      Royal University Hospital, Saskatoon,  Saskatchewan,  S7N 0W8,  Canada

United Kingdom
      Royal Victoria Hospital, Belfast, Co. Antrim, N.Ireland,  BT12 6BA,  United Kingdom

      Princess of Wales Hospital (Grimsby), Grimsby, South Humberside,  DN33 2BA,  United Kingdom

      Castle Hill Hospital, Cottingham, Hull,  HU16 5JG,  United Kingdom

      St. Thomas' Hospital, London,  SE1 7EH,  United Kingdom

      Selly Oak Hospital, Selly Oak, Birmingham,  B29 6JD,  United Kingdom

      Scunthorpe General Hospital, Scunthorpe, N. Lincolnshire,  DN15 7BH,  United Kingdom

      Stepping Hills Hospital, Stockport, Cheshire,  SK2 7JE,  United Kingdom

      City Hospital (Birmingham), Birmingham,  B18 7QH,  United Kingdom

      Northern General Hospital, Sheffield, Yorkshire,  S5 7AU,  United Kingdom

      Newham General Hospital, Plaistow, London,  E13 8SL,  United Kingdom

      Derbyshire Royal Infirmary, Derby,  DE1 2QY,  United Kingdom

      York District Hospital, York, North Yorkshire,  YO3 7HE,  United Kingdom

      Cardiology Research Unit Sussex House, Brighton, Sussex,  BN2 1ES,  United Kingdom

      Pinderfields General Hospital, Wakefield,  WF1 4DG,  United Kingdom

      Wythenshawe Hospital, Wythenshawe, Manchester,  M23 9LT,  United Kingdom

      Blackpool Victoria Hospital, Blackpool, Lancashire,  FY3 8NR,  United Kingdom

      Bedford Hospital, Bedford,  MK42 9DJ,  United Kingdom

      Northwick Park Hospital and Institue for Medical R, Harrow, Middlesex,  HA1 3UJ,  United Kingdom

      Royal Alexandra Hospital, Paisley, Renfrewshire, Scotland,  PA2 9PN,  United Kingdom

      Bridlington and District Hospital, Bridlington,  YO16 4QP,  United Kingdom

      St. James' University Hospital, Leeds, W. Yorkshire,  LS9 7TF,  United Kingdom

      Pontefract General Infirmary, Pontefract, W. Yorkshire,  WF8 1PL,  United Kingdom

      Glasgow Western Infirmary, Glasgow, Uk, Glasgow,  G12 8QQ,  United Kingdom

      King Geroge Hospital, Ilford, Essex,  IG3 8YB,  United Kingdom

      South Cleveland Hospital, Middlesborough, Cleveland,  TS4 3BW,  United Kingdom

      Torbay District General, Torbay, Uk, Torbay, Devon,  TQ2 7AA,  United Kingdom

      Derriford Hosptial, Devon,  PL6 8DH,  United Kingdom

      Barnsley District General, Barnsley, S.Yorkshire,  S75 2EP,  United Kingdom

      Luton and Dunstable Hospital, Luton, Beds,  LU4 0DZ,  United Kingdom

More Information

Study ID Numbers:  442
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  December 29, 2000
ClinicalTrials.gov Identifier:  NCT00007683
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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