Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function (TOPCAT)

February 11, 2015 updated by: HealthCore-NERI

Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)

The purpose of this study is to evaluate the effectiveness of aldosterone antagonist therapy in reducing cardiovascular mortality, aborted cardiac arrest, and heart failure hospitalization in patients who have heart failure with preserved systolic function.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND:

Heart failure (HF) is a major cause of morbidity and mortality, particularly in older people. Indeed, it is the most common discharge diagnosis in patients older than 65 years. As the United States population ages, heart failure will continue to grow as a public health concern. Therapeutic trials of heart failure have dealt almost exclusively with patients who have systolic dysfunction. However, there is now an emerging awareness that nearly half of the patients with heart failure have preserved systolic function and that the survival of these patients is adversely affected. This study is a randomized clinical trial of a novel therapeutic approach, specifically the use of spironolactone, an aldosterone antagonist, in treating these patients. While this treatment has been shown to be useful in treating heart failure with reduced systolic function, it has not been studied in patients with preserved systolic function.

Patients with heart failure and preserved systolic function have a poor prognosis. The annual mortality rate is intermediate between the prognosis for those without heart failure and for those with heart failure and reduced systolic function. For instance, Family Health Study participants with heart failure and preserved systolic function had a mortality rate of 9% compared to 3% for their age- and gender-matched controls. The mortality rate was 19% in heart failure patients with reduced systolic function heart failure compared to 4% for their matched controls.

As heart failure develops, neurohormones are released that initially improve cardiac output but ultimately contribute to progression of left ventricular dysfunction. The renin-angiotensin-aldosterone system is an important part of this compensatory response. Aldosterone levels may rise to 20 times normal levels in heart failure and aldosterone contributes to the development of myocardial fibrosis. Spironolactone is a potassium-sparing diuretic that acts on the distal tubule, inhibiting sodium and potassium ion exchange. There are several potential beneficial actions, including prevention of cardiac fibrosis. A recent trial evaluated spironolactone in patients with systolic dysfunction heart failure. Spironolactone treatment caused a 30% reduction in mortality compared to placebo (p< 0.001). The improvement resulted from a reduction in all cause mortality. More recently, the Eplerenone Post-Myocardial Infarction (MI) study showed that this aldosterone antagonist significantly reduces mortality despite background treatment with an angiotensin-converting enzyme (ACE) inhibitor and beta-blocker. Advantages of using spironolactone in this study are that it is commercially available, inexpensive, and no longer under patent (therefore this study will not be done by industry). Also, there is a clear physiologic rationale for its use, and the side effect profile is well understood. The study enrolled subjects who had preserved systolic function with heart failure and who met clearly defined eligibility criteria that were selected to make the results widely generalizable to clinical practice.

DESIGN NARRATIVE:

This is a randomized, double-blinded, placebo-controlled trial of aldosterone antagonist therapy (15 mg dose spironolactone or placebo; titrated up to 30 or 45 mg/day) in 3,445 adult patients with heart failure and preserved systolic function. Patients were recruited from August 2006 through January 2012, treated, and will be followed through June 2013. Approximately 270 clinical sites in six countries were subcontracted by the clinical trial coordinating center. Subject visits to a clinical center will occur every four or six months. Data collected include demographic and clinical data, including the results of history and physical exams, laboratory and imaging data, repository specimens for special physiology studies, and genetic studies. Additionally, data regarding quality of life and compliance with assigned treatment will also be collected and assessed.

Study Type

Interventional

Enrollment (Actual)

3445

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1119ACN
        • CIPREC
      • Buenos Aires, Argentina, 1425
        • IMAI Research
      • Buenos Aires, Argentina, C1426 ANZ
        • Instituto Cardiologico Ezpecializado S.R.L
      • Buenos Aires, Argentina, J846
        • Clinica IMA
      • Cordoba, Argentina, X500AAW
        • Clinica Privada del Prado
      • Rosario Santa Fe, Argentina, 2000
        • Instituto de Investigaciones Clinicas de Rosario
      • Salta, Argentina, A4406CLA
        • Hospital San Bernardo
      • Santa Fe, Argentina, 3000
        • Centro de Investigaciones Clínicas Del Litoral SRL
      • Santa Fe, Argentina
        • Sanatorio Mayo S.A.
      • Tucuman, Argentina, T4000NIL
        • Centro Privado de Cardiología
      • Tucuman, Argentina
        • Centro Modelo de Cardiologia
      • Tucuman, Argentina
        • Instituto de Cardiologia SRL
    • Buenos Aires
      • Bahia Blanca, Buenos Aires, Argentina, B80001JH
        • Instituto de Investigaciones Clinicas de Bahia Blanca
      • Coronel Suarez, Buenos Aires, Argentina, B7540GHD
        • Clinica Coronel Suárez
      • La Plata, Buenos Aires, Argentina, B1900 AXI
        • Hospital Italiano de La Plata
      • Mar del Plata, Buenos Aires, Argentina, B7600 FZN
        • Instituto de Investigaciones clinicas de Mar del Plata
      • Quilmes, Buenos Aires, Argentina, 1878
        • Instituto de Investigaciones Clínicas de Quilmes
    • Rio Negro
      • Cipolletti, Rio Negro, Argentina, 8324
        • Policlinico Modelo de Cipoletti
  • Brazil
      • Belo Horizonte, Brazil
        • Hospital Felicio Rocho
      • Belo Horizonte, Brazil
        • Santa Casa de Belo Horizonte
      • Campinas, Brazil
        • HMCP PUC Campinas
      • Curitiba Parana, Brazil
        • Irmandade da Santa Casa de Misericórdia de Curitiba
      • Goias, Brazil
        • Hospital Das Clinicas Da Universidade Federal De Goias
      • Marilia Sao Paulo, Brazil
        • Instituto do Coracao de Marília
      • Passo Fundo, Brazil
        • Hospital São Vicente de Paulo
      • Pernambuco, Brazil
        • PROCAPE
      • Porto Alegre, Brazil, 90035-903
        • Hospital de Clínicas de Porto Alegre
      • Porto Alegre, Brazil
        • Hospital Mae de Deus
      • Rio de Janeiro, Brazil
        • Hospital Universitário Pedro Ernesto
      • Rio de Janeiro, Brazil
        • Santa Casa de Misericordia do Rio de Janeiro
      • San Paulo, Brazil
        • Instituto de Molestias Cardiosvaculares
      • Santa Catarina, Brazil
        • Instituto de Cardiologia de Santa Catarina
      • Sao Paulo, Brazil
        • INCOR FMUSP
      • Sao Paulo, Brazil
        • UNIFESP/Hospital Sao Paulo
      • Uberlandia, Brazil
        • Instituto do Coração do Triângulo Mineiro
  • Canada
      • Edmonton, Canada
        • Misericordia Hospital - Cardiac Sciences
      • Longueuil, Canada
        • CDRC Rive-Sud
      • Montreal, Canada
        • SMBD Jewish General Hospital
      • Saskatoon, Canada
        • Saskatchewan Heart Centre
      • Surrey, Canada
        • Cardiology Clinical Trials - Surrey Memorial Hospital
      • Trois Rivieres, Canada
        • Centre Hospitalier de Trois-Rivieres
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N1
        • University of Calgary
    • British Columbia
      • New Westminster, British Columbia, Canada, V3L 3W4
        • Fraser Clinical Trials Inc.
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H2A6
        • St. Boniface General Hospital
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
        • Health Science Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3A7
        • Capital District Health Authority
    • Ontario
      • Cambridge, Ontario, Canada, N1R 7R1
        • Dr. Saul Vizel Cardiac Research Office
      • Cornwall, Ontario, Canada, K6H 4M4
        • Cornwall Clinical Trials
      • Hamilton, Ontario, Canada, L8L 2X2
        • Hamilton Health Sciences - General Site
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Center
      • Ottawa, Ontario, Canada, K1Y 4W7
        • Ottawa Heart Institute
      • Sudbury, Ontario, Canada, P3C 5K7
        • Dr. Gurcharan Syan (PP)
      • Toronto, Ontario, Canada, M5G1X5
        • Mount Sinai Hospital
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital
    • Quebec
      • Fleurimont, Quebec, Canada, J1H 5N4
        • CHUS - Hôpital Fleurimont
      • Granby, Quebec, Canada, J2G 1T7
        • Service de la Recherche
      • Laval, Quebec, Canada, H7M 3L9
        • Cite de La Sante de Laval
      • Levis, Quebec, Canada, G6V 4Z5
        • Clinique Cardiologie Levis
      • Montreal, Quebec, Canada, H1T 1C8
        • Montreal Heart Institute
      • Montreal, Quebec, Canada, H3A 1A1
        • Royal Victoria Hospital
      • Montreal, Quebec, Canada, A4J 1C5
        • Hopital Du Sacre Coeur de Montreal
      • Montreal, Quebec, Canada, H2W 1T8
        • CHUM - Hotel Dieu
      • Montreal, Quebec, Canada, H2W IT8
        • CHUM Hôtel Dieu
      • Montreal, Quebec, Canada, H3G IA4
        • Montreal General Hospital
      • Quebec City, Quebec, Canada, G1J 1Z6
        • Centre de Recherche Clinique de Quebec
      • Sainte Charles Borromee, Quebec, Canada, J6E 6J2
        • Centre Hosp Regional de Lanaudiere
      • St. George, Quebec, Canada, G5Y 4T8
        • C.S.S.S.B.
      • Ste-Foy, Quebec, Canada, GIV 4G5
        • Hôpital Laval
      • Terrebonne, Quebec, Canada, J6V 2H2
        • CSSS du Sud de Lanaudiere (Hopital Pierre-Le Gardeur)
      • Thetford-Mines, Quebec, Canada, G6G 2V4
        • Centre De Sante et De Services Sociaux De Thetford
  • Georgia
      • Kutaisi, Georgia, 4600
        • L &J Clinic
      • Tbilisi, Georgia, 0102
        • Tbilisi State Medical University Clinic #1
      • Tbilisi, Georgia, 0141
        • Cardio-Reanimation Centre
      • Tbilisi, Georgia, 0154
        • Multiprofile Clinical Hospital of Tbilisi #2
      • Tbilisi, Georgia, 0159
        • Emergency Cardiology Centre
      • Tbilisi, Georgia, 0159
        • National Center of Therapy
      • Tbilisi, Georgia, 0179
        • Diagnostic Services Clinic
      • Tbilisi, Georgia, 0186
        • Clinic of Angiocardiology "ADAPTI"
      • Tibilisi, Georgia, 0144
        • Cardiology Clinic
  • Russian Federation
      • Barnaul, Russian Federation, 656038
        • Altay State Medical University of federal agency of public health and social progress RF
      • Barnaul, Russian Federation, 656099
        • Municipal Health Care Institution "City Hospital #1"
      • Kaliningrad, Russian Federation, 236016
        • Kaliningrad Region Hospital
      • Kemerovo, Russian Federation, 650002
        • Kemerovo Cadiologiy Dispensary, Kemerovo Medical Academy
      • Kemerovo, Russian Federation, 650036
        • Nonstate Healthcare Institution
      • Krasnodar, Russian Federation, 350086
        • State Healthcare Institution "Region Clinical Hospital #1
      • Moscow, Russian Federation, 101990
        • National Research Center for Preventitive Medicine
      • Moscow, Russian Federation, 111539
        • Russian State Medical University, Hospital Therapy Department #1
      • Moscow, Russian Federation, 115093
        • State Education High Professional Education Russian State Medical University
      • Moscow, Russian Federation, 129090
        • Federal State Institution "Outpatient clinic #3 of President's Management Department of Russian Fede
      • Moscow, Russian Federation, 777020
        • Research Institute of Physico-Chemical Medicine Center for Atheosclerosis and Laboratory
      • Moscow, Russian Federation
        • Non State Health Care Institution Central Hospital #6 of Russian Railways JSC
      • Novosibirsk, Russian Federation, 630008
        • Novosibirsk Municipal Clinical Emergency Hosp. # 2
      • Saint Petersburg, Russian Federation, 193312
        • Saint-Petersburg State Healthcare Institution "City Alexander's Hospital"
      • Saint Petersburg, Russian Federation, 198205
        • Saint-Petersburg State Institution of Health Protection, "City Hosptial # 15"
      • Saint Petersburg, Russian Federation
        • Chair of Nephrology and Dialysis of St Petersburg State Medical University
      • Saint-Petersburg, Russian Federation, 190000
        • Public Institution of Health City Hospital # 28
      • Saint-Petersburg, Russian Federation, 194291
        • Federal State Health Care Institution
      • Saint-Petersburg, Russian Federation, 198013
        • Medico- Military Academy, Navy Therapy Dept
      • Saint-Petersburg, Russian Federation, 199106
        • Saint-Petersburg State Health Institution "Pokrovskaya City Hospital"
      • Saratov, Russian Federation, 410028
        • Federal State Institution
      • Saratov, Russian Federation, 410054
        • State Educational Institution of High Professional Education Saratov State Medical University
      • St. Petersberg, Russian Federation, 194156
        • Almasov research institute of Cardiology
      • St. Petersburg, Russian Federation, 192242
        • State Institution Saint-Petersburg Dzhanelidze Scientific
      • St. Petersburg, Russian Federation, 194017
        • Saint-Petersburg Clinical Hospital of RAMS, policlinic department
      • St. Petersburg, Russian Federation, 194354
        • Saint-Petersburg State Health Care Institution "City Hospital of Saint George the Martyr"
      • St. Petersburg, Russian Federation, 195221
        • Non-state Health Care Institution
      • St. Petersburg, Russian Federation, 196247
        • City Hospital #26
      • St. Petersburg, Russian Federation, 196247
        • City Hospital No 26
      • St. Petersburg, Russian Federation, 197089
        • Chair and Department of Hospital Therapy
      • Tomsk, Russian Federation, 634012
        • State Institition Research Institution of Cardiology of Tomsk
      • Volgograd, Russian Federation, 400001
        • State Educational institution of Higher Professional Education "Volgograd State Medical University o
      • Voronezh, Russian Federation, 396018
        • State Health Care Institution "Voronezh Regional Clinical Consultative & Diagnostic Centre"
      • Yaroslavl, Russian Federation, 150030
        • City Healthcare Institution Clinical Hospital #8
      • Yaroslavl, Russian Federation, 150068
        • Yaroslavl Regional Clinical Hospital
    • Leningrad Region
      • Gatchina, Leningrad Region, Russian Federation, 188300
        • Municipal Healthcare Institution <>
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Glendale, Arizona, United States, 85306
        • Cardiovascular Consultants, Ltd.
      • Phoenix, Arizona, United States, 85012
        • Carl T. Hayden VA Medical Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Central Arkansas Veterans Healthcare System
      • Little Rock, Arkansas, United States, 72205
        • Heart Clinic Arkansas
    • California
      • Burbank, California, United States, 91505
        • Cynthia Thaik
      • Fresno, California, United States, 93703
        • Fresno VA Medical Center
      • Los Angeles, California, United States, 90015
        • Clinica Medica San Miguel
      • Los Angeles, California, United States, 90048
        • CAPRI
      • Los Angeles, California, United States, 90073
        • VA Medical Center West Los Angeles
      • Northridge, California, United States, 91325
        • Mehrdad Kevin Ariani, MD, Inc.
      • Sacremento, California, United States, 95829
        • UC Davis Medical Center
      • Salinas, California, United States, 93901
        • Central Coast Cardiology
      • San Diego, California, United States, 92134
        • Naval Medical Center San Diego
      • Sylmar, California, United States, 91342
        • Olive View - UCLA Medial Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Health Sciences Center
      • Greeley, Colorado, United States, 80631
        • Cardio-Vascular Institute
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut Health Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Hospital Center
      • Washington, District of Columbia, United States, 20422
        • Washington DC VA Hospital
      • Washington DC, District of Columbia, United States, 20060'
        • Howard University Hospital
    • Florida
      • Daytona Beach, Florida, United States, 32114
        • Daytona Heart Group
      • Ft. Lauderdale, Florida, United States, 33316
        • M & O Clinical Research, LLC
      • Ft. Pierce, Florida, United States, 34950
        • Florida Heart Center
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Florida
      • Rockledge, Florida, United States, 37955
        • Brevard Cardiovascular Research Associates, Inc
      • Tallahassee, Florida, United States, 32308
        • Tallahassee Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30310
        • Morehouse School Of Medicine
      • Atlanta, Georgia, United States, 30303
        • Emory University at Grady Health System
      • Atlanta, Georgia, United States, 30342
        • Northside Cardiology Center
      • Marietta, Georgia, United States, 30060
        • InnovaMed Alliance
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago Medical Center
      • Chicago, Illinois, United States, 60657
        • Northwestern University
      • Elk Grove Village, Illinois, United States, 60007
        • CardioVascular Research Foundation
      • Peoria, Illinois, United States, 61614
        • HeartCare Midwest
      • Peoria, Illinois, United States, 61606
        • Heart, Lung and Vascular Institute
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • The Care Group, Llc
      • Munster, Indiana, United States, 46321
        • Cardiovascular Research Of Northwest Indiana, Llc
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Baptist Healthcare System, Inc. d/b/a Baptist Hospital East
    • Louisiana
      • Houma, Louisiana, United States, 70363
        • Leonard J. Chabert Medical Center
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Maine
      • Bangor, Maine, United States, 04401
        • Northeast Cardiology
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Largo, Maryland, United States, 20774
        • Kaiser Permanente
      • Randallstown, Maryland, United States, 21133
        • Northwest Hospital
      • Salisbury, Maryland, United States, 21804
        • Delmarva Heart Research Foundation
      • Silver Spring, Maryland, United States, 20910
        • Associates in Cardiology, PA
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02135
        • Caritas St. Elizabeth's Medical Center
      • Boston, Massachusetts, United States, 02118
        • Boston University Medical Center
      • Chelmsford, Massachusetts, United States, 01824
        • Merrimack Valley Cardiology Associates
      • East Bridgewater, Massachusetts, United States, 02333
        • Compass Medical East Bridgewater
      • Haverhill, Massachusetts, United States, 01830
        • Pentucket Medical Associates
      • Natick, Massachusetts, United States, 01760
        • Charles River Medical Associates
      • North Dartmouth, Massachusetts, United States, 02747
        • Hawthorn Medical Associates
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Veterans Affairs Ann Arbor Health Care System
      • Dearborn, Michigan, United States, 48123
        • Oakwood Hospital and Medical Center
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Detroit VA Medical Center
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Health Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Medical Center
    • Missouri
      • St. Joseph, Missouri, United States, 64506
        • Heartland Regional Medical Clinic
    • Montana
      • Kalispell, Montana, United States, 59901
        • Glacier View Cardiology
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Bryan LGH Heart Institute
      • Omaha, Nebraska, United States, 68131
        • The Creighton Cardiac Center
    • New Jersey
      • Browns Mills, New Jersey, United States, 08015
        • Deborah Heart and Lung Center
      • Elmer, New Jersey, United States, 08318
        • Cardiovascular Associates of the Delaware Valley
      • Haddon Heights, New Jersey, United States, 08035
        • Cardiovascular Associates of the Delaware Valley
      • Linden, New Jersey, United States, 07036
        • NJ Heart
      • Paterson, New Jersey, United States, 07503
        • St. Joseph's Regional Medical Center
      • Ridgewood, New Jersey, United States, 07450
        • The Valley Hospital
      • Somerset, New Jersey, United States, 08873
        • Electrophysiology Research Foundation
      • Toms River, New Jersey, United States, 08755
        • Community Medical Center
      • West Orange, New Jersey, United States, 07052
        • New Jersey Cardiology Associates
    • New York
      • Bronx, New York, United States, 10457
        • Bronx-Lebanon Hospital Center
      • Brooklyn, New York, United States, 11215
        • New York Methodist Hospital
      • Buffalo, New York, United States, 14203
        • Research Foundation State University of New York at Buffalo
      • Buffalo, New York, United States, 14215
        • Buffalo Heart Group, LLC
      • Jamaica, New York, United States, 11418
        • Jamaica Hospital Medical Center
      • Kingston, New York, United States, 12401
        • Mid Valley Cardiology
      • Mineola, New York, United States, 11501
        • Winthrop Cardiology Associates
      • New Rochelle, New York, United States, 10802
        • Soundshore Medical Center of Westchester
      • New York, New York, United States, 10016
        • NYU School of Medicine
      • New York, New York, United States, 10019
        • St. Lukes Roosevelt
      • Northport, New York, United States, 11768
        • Northport VA Medical Center
      • Rochester, New York, United States, 14618
        • University of Rochester Medical Center
      • Smithtown, New York, United States, 11787
        • Lewin, Fagen, and Lown, MD, PC
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical Center
      • Syracuse, New York, United States, 13210
        • Syracuse VA Medical Center
    • North Carolina
      • Concord, North Carolina, United States, 28025
        • Northeast Medical Center
      • Durham, North Carolina, United States, 27705
        • Durham VA Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati
      • Cincinnati, Ohio, United States, 45219
        • The Lindner Clinical Trial Center
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland/Case Western Reserve University
      • Columbus, Ohio, United States, 43205
        • Ohio State University Hospital East
      • Dayton, Ohio, United States, 45428
        • VAMC Dayton
      • Garfield Heights, Ohio, United States, 44125
        • CCHS Clinical Research Office/Marymount Hospital
      • Mayfield Heights, Ohio, United States, 44124
        • CCHS Clinical Research Office/ Hillcrest Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma City VA Medical Center
      • Oklahoma City, Oklahoma, United States, 73103
        • COR Clinical Research
      • Oklahoma City, Oklahoma, United States, 73210
        • Oklahoma Foundation for Cardiovascular Research
      • Tulsa, Oklahoma, United States, 74137
        • Oklahoma Heart Institute
    • Oregon
      • Bend, Oregon, United States, 97701
        • St. Charles Health System
      • Portland, Oregon, United States, 97213
        • Providence Heart and Vascular Institute
    • Pennsylvania
      • Camp Hill, Pennsylvania, United States, 17011
        • Capital Area Research
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Erie, Pennsylvania, United States, 16507
        • Medicor Associates, Inc
      • Hershey, Pennsylvania, United States, 17033
        • The Milton S. Hershey Medical Center
      • Lancaster, Pennsylvania, United States, 17603
        • Lancaster Heart and Stroke Foundation
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital- Dept. of Family and Community Health
      • Philadelphia, Pennsylvania, United States, 19153
        • Eastwick Primary Care
      • Pittsburgh, Pennsylvania, United States, 15240
        • Pittsburgh VA Healthcare System
      • West Reading, Pennsylvania, United States, 19611
        • The Reading Hospital and Medical Center
    • Rhode Island
      • Pawtucket, Rhode Island, United States, 02860
        • Memorial Hospital Rhode Island
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • Vamc - Charleston, Sc
    • South Dakota
      • Ft. Meade, South Dakota, United States, 57741
        • Black Hills VA Health Care System
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The Stern Cardiovascular Center
      • Memphis, Tennessee, United States, 38163
        • University of Tennessee Health Science Center
      • Memphis, Tennessee, United States, 38120
        • Memphis Heart Clinic
      • Memphis, Tennessee, United States, 38104
        • Memphis VA Medical Center
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Heart and Vascular Institute
    • Texas
      • Arlington, Texas, United States, 76014
        • DCT - APHC, LLC dba Discovery Clinical Trials
      • Dallas, Texas, United States, 75216
        • Dallas VA Medical Center
      • Dallas, Texas, United States, 75231
        • Cardiovascular Research Institute of Dallas
      • Dallas, Texas, United States, 75390
        • U.T. Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Research Institute
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Cntr.
      • Lackland, Texas, United States, 78236
        • Wilford Hall Medical Center
      • Odessa, Texas, United States, 79763
        • Texas Tech University Health Sciences Center
      • San Antonio, Texas, United States, 78229
        • Cardiology Clinic of San Antonio
      • Tyler, Texas, United States, 75701
        • Tyler Cardiovascular Consultants
    • Utah
      • Murray, Utah, United States, 84157
        • LDS Hospital
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Chesapeake, Virginia, United States, 23320
        • Cardiovascular Associates Ltd.
      • Norfolk, Virginia, United States, 23507
        • Sentara Cardiovascular Research Institute
    • Washington
      • Kirkland, Washington, United States, 98034
        • Evergreen Healthcare
      • Olympia, Washington, United States, 98506
        • Providence St. Peter Hospital
      • Port Orchard, Washington, United States, 98366
        • Sound Health Research
      • Seattle, Washington, United States, 98195
        • University of Washington
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • CAMC Health Education and Research Institute
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin-Madison
      • Madison, Wisconsin, United States, 53705
        • William S. Middleton Memorial VA Hospital
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Heart and Vascular Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

  • Heart failure as defined by at least one of symptom (paroxysmal nocturnal dyspnea; orthopnea; or dyspnea on mild or moderate exertion) at the time of screening and at least one sign (any rales post cough; jugular venous pressure(JVP) greater than or equal to 10cm of water(H2O); lower extremity edema; or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly) within 12 months prior to study entry:
  • left ventricular ejection fraction greater than or equal to 45% (per local reading); the ejection fraction must have been obtained within 6 months prior to randomization and after any MI or other event that would affect ejection fraction
  • Controlled systolic blood pressure(BP), defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP
  • Serum potassium less than 5.0 mmol/L prior to randomization
  • At least one hospital admission for which heart failure was a major component of the hospitalization some time within the 12 months prior to study entry OR brain natriuretic peptide (BNP) greater than or equal to 100pg/ml or N-terminal pro-BNP greater than or equal to 360pg/ml within the 60 days prior to study entry
  • Women of child-bearing potential must have a negative serum/urine pregnancy test within 72 hours prior to randomization, must not be lactating, and must agree to use an effective method of contraception during the entire course of study participation
  • Willing to comply with scheduled visits
  • Informed consent form signed by the subject prior to participation in the trial

EXCLUSION CRITERIA:

  • Severe systemic illness with an expected life expectancy of less than 3 years
  • Chronic pulmonary disease requiring home O2, oral steroid therapy, or hospitalization for exacerbation within 12 months of study entry, or significant chronic pulmonary disease in the opinion of the investigator
  • Known infiltrative or hypertrophic obstructive cardiomyopathy or known pericardial constriction
  • Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial
  • Atrial fibrillation with a resting heart rate greater than 90 bpm
  • MI in the past 90 days
  • Coronary artery bypass graft surgery in the past 90 days
  • Percutaneous coronary intervention in the past 30 days
  • Heart transplant recipient
  • Currently implanted left ventricular assist device
  • Stroke in past 90 days
  • Systolic BP (SBP) greater than 160 mm Hg
  • Known orthostatic hypotension
  • Gastrointestinal disorder that could interfere with study drug absorption
  • Use of any aldosterone antagonist or potassium sparing medication in the last 14 days or any known condition that would require the use of an aldosterone antagonist during study participation;
  • Known intolerance to aldosterone antagonists
  • Current lithium use
  • Current participation (including prior 30 days) in any other therapeutic trial
  • Any condition that, in the opinion of the investigator, may prevent the participant from adhering to the trial protocol
  • History of hyperkalemia (serum potassium greater than or equal to 5.5mmol/L) in the past 6 months or serum potassium greater than or equal to 5.0mmol/L within the past 2 weeks
  • Severe renal dysfunction, defined as an estimated glomerular filtration rate(GFR) less than 30ml/min. Participants with serum creatinine greater than or equal to 2.5mg/dl are also excluded even if their GFR is greater than or equal to 30ml/min
  • Known chronic hepatic disease, defined as aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels greater than 3.0 times the upper limit of normal as read at the local lab.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Placebo of spironolactone
Drug: Placebo
Placebo of spironolactone
EXPERIMENTAL: Spironolactone
Spironolactone (an aldosterone antagonist) is supplied as 15 mg tablets. Drug is taken orally by subjects. The initial study drug dose is 15 mg/day (one tablet) and may be titrated up to 30 mg/day (two tablets) or 45 mg/day (three tablets). Subjects are on study drug for the duration of the trial.
Drug: Spironolactone
Spironolactone (an aldosterone antagonist) is supplied as 15 mg tablets. Drug is taken orally by subjects. The initial study drug dose is 15 mg/day (one tablet) and may be titrated up to 30 mg/day (two tablets) or 45 mg/day (three tablets). Subjects are on study drug for the duration of the trial.
Other Names:
  • aldosterone antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite Outcome of Cardiovascular Mortality, Aborted Cardiac Arrest, or Hospitalization for the Management of Heart Failure, Whichever Occurred First
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular Mortality
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Aborted Cardiac Arrest
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of aborted cardiac arrest
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Hospitalization for the Management of Heart Failure
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of a hospitalization for the management of heart failure
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
All-cause Mortality
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Composite Outcome of Cardiovascular Mortality or Cardiovascular-related Hospitalization (i.e., Hospitalization for Myocardial Infarction(MI), Stroke, or the Management of Heart Failure), Whichever Occurred First
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Cardiovascular-related Hospitalization
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Hospitalization for MI, stroke or the management of heart failure, whichever occurred first
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Total Hospitalizations (Including Repeat Hospitalizations) for the Management of Heart Failure
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Composite Outcome of Sudden Death or Aborted Cardiac Arrest, Whichever Occurred First
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
New Onset Diabetes Mellitus, Among Subjects Without a History of Diabetes Mellitus at Baseline.
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of new onset diabetes mellitus among subjects without a history of diabetes mellitus at baseline.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Development of Atrial Fibrillation, Among Subjects Without a History of Atrial Fibrillation at Baseline.
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of atrial fibrillation among subjects without a history of atrial fibrillation at baseline
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Myocardial Infarction
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of myocardial infarction
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Stroke
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of stroke
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Deterioration of Renal Function
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of a deterioration of renal function. The TOPCAT protocol defines deterioration of renal function as occurring if a subject has a serum creatinine value which is at least double the baseline value for that subject, and is also above the upper limit of normal (assumed to be 1.0 mg/dL for females and 1.2 mg/dL for males.)
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Composite Outcome of Sudden Death, Aborted Cardiac Arrest, or Hospitalization for the Management of Ventricular Tachycardia, Whichever Occurred First
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire.
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Average post-baseline quality of life, taking into consideration baseline quality of life, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. The KCCQ was administered at the following study visits: baseline, month 4, month 12 and annually thereafter.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Quality of Life, as Measured by the EuroQOL Visual Analog Scale.
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Average post-baseline quality of life, taking into consideration baseline quality of life, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.

The EuroQOL visual analog scale (EQ5D) is a single-item, self-administered instrument that quantifies current health status. Scores can range from 0-100, in which higher scores reflect better health status. The EQ5D was administered at the following study visits: baseline, month 4, month 12 and annually thereafter.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Quality of Life, as Measured by McMaster Overall Treatment Evaluation Questionnaire.
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Average post-baseline quality of life, taking into consideration baseline quality of life and treatment group.

The McMaster Overall Treatment Evaluation questionnaire is a self-administered 3-item instrument that measures a patient's perception of change in their health-related quality of life since the start of therapy. The questionnaire consists of a single question - "Since treatment started, has there been any change in your activity limitation, symptoms and/or feelings related to your heart condition?" Scores can range from -7 to +7, and higher scores reflect better health status. The questionnaire was administered at the following study visits: month 4 and month 12. Valid translations of this questionnaire were only available for subjects enrolled in the United States, Canada and Argentina.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Depression Symptoms, as Measured by Patient Health Questionnaire.
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Average post-baseline depression, taking into consideration baseline depression, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.

The Patient Health Questionnaire (PHQ) is a 10-item, self-administered instrument for screening, diagnosing, monitoring and measuring the severity of depression. Scores can range from 0-27, in which lower scores reflect better mental health status. The PH-Q was administered at the following study visits: baseline, month 12 and annually thereafter. Valid translations of this questionnaire were only available for subjects enrolled in the United States and Canada.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Hospitalization for Any Reason
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
First incidence of a hospitalization for any reason
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Potassium
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Average post-baseline Potassium, taking into consideration baseline Potassium, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Serum Creatinine
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Average post-baseline serum creatinine, taking into consideration baseline serum creatinine, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Sodium
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Average post-baseline Sodium, taking into consideration baseline Sodium, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Chloride
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Average post-baseline Chloride, taking into consideration baseline Chloride, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Estimated Glomerular Filtration Rate (GFR)
Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Average post-baseline GFR, taking into consideration baseline GFR, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

HealthCore-NERI

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Sonja M. McKinlay, PhD, New England Research Institutes, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (ACTUAL)

June 1, 2013

Study Completion (ACTUAL)

June 1, 2013

Study Registration Dates

First Submitted

October 15, 2004

First Submitted That Met QC Criteria

October 14, 2004

First Posted (ESTIMATE)

October 15, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

March 2, 2015

Last Update Submitted That Met QC Criteria

February 11, 2015

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 160
  • HHSN268200425207C (OTHER_GRANT: NIH contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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