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

Cardiovascular Diseases Clinical Trial

— TOPCAT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094302
• Other study ID #: 160
• Secondary ID: HHSN268200425207
• Status: Completed
• Phase: Phase 3
• First received: October 15, 2004
• Last updated: February 11, 2015
• Start date: August 2006
• Est. completion date: June 2013

Study information

• Verified date: January 2014
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3445
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Heart Diseases
• Heart Failure
• Heart Failure, Congestive

Intervention

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.
• Placebo
Placebo of spironolactone

Locations

Country	Name	City	State
Argentina	Instituto de Investigaciones Clinicas de Bahia Blanca	Bahia Blanca	Buenos Aires
Argentina	CIPREC	Buenos Aires
Argentina	Clinica IMA	Buenos Aires
Argentina	IMAI Research	Buenos Aires
Argentina	Instituto Cardiologico Ezpecializado S.R.L	Buenos Aires
Argentina	Policlinico Modelo de Cipoletti	Cipolletti	Rio Negro
Argentina	Clinica Privada Del Prado	Cordoba
Argentina	Clinica Coronel Suarez	Coronel Suarez	Buenos Aires
Argentina	Hospital Italiano de La Plata	La Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas de Mar Del Plata	Mar del Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas de Quilmes	Quilmes	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas de Rosario	Rosario Santa Fe
Argentina	Hospital San Bernardo	Salta
Argentina	Centro de Investigaciones Clinicas del Litoral SRL	Santa Fe
Argentina	Sanatorio Mayo S.A.	Santa Fe
Argentina	Centro Modelo de Cardiología	Tucuman
Argentina	Centro Privado de Cardiologia	Tucuman
Argentina	Instituto de Cardiologia SRL	Tucuman
Brazil	Hospital Felicio Rocho	Belo Horizonte
Brazil	Santa Casa De Belo Horizonte	Belo Horizonte
Brazil	HMCP PUC Campinas	Campinas
Brazil	Irmandade da Santa Casa de Misericordia de Curitiba	Curitiba Parana
Brazil	Hospital das Clinicas da Universidade Federal de Goias	Goias
Brazil	Instituto do Coracao de Marilia	Marilia Sao Paulo
Brazil	Hospital Sao Vicente de Paulo	Passo Fundo
Brazil	PROCAPE	Pernambuco
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Brazil	Hospital Mae De Deus	Porto Alegre
Brazil	Hospital Universitario Pedro Ernesto	Rio de Janeiro
Brazil	Santa Casa de Misericordia do Rio de Janeiro	Rio de Janeiro
Brazil	Instituto de Molestias Cardiosvaculares	San Paulo
Brazil	Instituto de Cardiologia de Santa Catarina	Santa Catarina
Brazil	Incor Fmusp	Sao Paulo
Brazil	UNIFESP/Hospital Sao Paulo	Sao Paulo
Brazil	Instituto do Coracao do Triangulo Mineiro	Uberlandia
Canada	University of Calgary	Calgary	Alberta
Canada	Dr. Saul Vizel Cardiac Research Office	Cambridge	Ontario
Canada	Cornwall Clinical Trials	Cornwall	Ontario
Canada	Misericordia Hospital - Cardiac Sciences	Edmonton
Canada	CHUS - Hopital Fleurimont	Fleurimont	Quebec
Canada	Service de la Recherche	Granby	Quebec
Canada	Capital District Health Authority	Halifax	Nova Scotia
Canada	Hamilton Health Sciences - General Site	Hamilton	Ontario
Canada	Cite de la Sante de Laval	Laval	Quebec
Canada	Clinique Cardiologie Levis	Levis	Quebec
Canada	London Health Sciences Center	London	Ontario
Canada	CDRC Rive-Sud	Longueuil
Canada	CHUM - Hotel Dieu	Montreal	Quebec
Canada	Chum Hotel Dieu	Montreal	Quebec
Canada	Hopital Du Sacre Coeur de Montreal	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	SMBD Jewish General Hospital	Montreal
Canada	Fraser Clinical Trials Inc.	New Westminster	British Columbia
Canada	Ottawa Heart Institute	Ottawa	Ontario
Canada	Centre de recherche clinique de Quebec	Quebec City	Quebec
Canada	Centre Hosp Regional de Lanaudiere	Sainte Charles Borromee	Quebec
Canada	Saskatchewan Heart Centre	Saskatoon
Canada	C.S.S.S.B.	St. George	Quebec
Canada	Health Science Centre	St. John's	Newfoundland and Labrador
Canada	Hopital Laval	Ste-Foy	Quebec
Canada	Dr. Gurcharan Syan (PP)	Sudbury	Ontario
Canada	Cardiology Clinical Trials - Surrey Memorial Hospital	Surrey
Canada	CSSS du Sud de Lanaudiere (Hopital Pierre-Le Gardeur)	Terrebonne	Quebec
Canada	Centre De Sante et De Services Sociaux De Thetford	Thetford-Mines	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Centre Hospitalier de Trois-Rivieres	Trois Rivieres
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Georgia	L &J Clinic	Kutaisi
Georgia	Cardio-Reanimation Centre	Tbilisi
Georgia	Clinic of Angiocardiology "ADAPTI"	Tbilisi
Georgia	Diagnostic Services Clinic	Tbilisi
Georgia	Emergency Cardiology Centre	Tbilisi
Georgia	Multiprofile Clinical Hospital of Tbilisi #2	Tbilisi
Georgia	National Center of Therapy	Tbilisi
Georgia	Tbilisi State Medical University Clinic #1	Tbilisi
Georgia	Cardiology Clinic	Tibilisi
Russian Federation	Altay State Medical University of federal agency of public health and social progress RF	Barnaul
Russian Federation	Municipal Health Care Institution "City Hospital #1"	Barnaul
Russian Federation	Municipal Healthcare Institution <>	Gatchina	Leningrad Region
Russian Federation	Kaliningrad Region Hospital	Kaliningrad
Russian Federation	Kemerovo Cadiologiy Dispensary, Kemerovo Medical Academy	Kemerovo
Russian Federation	Nonstate Healthcare Institution	Kemerovo
Russian Federation	State Healthcare Institution "Region Clinical Hospital #1	Krasnodar
Russian Federation	Federal State Institution "Outpatient clinic #3 of President's Management Department of Russian Fede	Moscow
Russian Federation	National Research Center for Preventitive Medicine	Moscow
Russian Federation	Non State Health Care Institution Central Hospital #6 of Russian Railways JSC	Moscow
Russian Federation	Research Institute of Physico-Chemical Medicine Center for Atheosclerosis and Laboratory	Moscow
Russian Federation	Russian State Medical University, Hospital Therapy Department #1	Moscow
Russian Federation	State Education High Professional Education Russian State Medical University	Moscow
Russian Federation	Novosibirsk Municipal Clinical Emergency Hosp. # 2	Novosibirsk
Russian Federation	Chair of Nephrology and Dialysis of St Petersburg State Medical University	Saint Petersburg
Russian Federation	Saint-Petersburg State Healthcare Institution "City Alexander's Hospital"	Saint Petersburg
Russian Federation	Saint-Petersburg State Institution of Health Protection, "City Hosptial # 15"	Saint Petersburg
Russian Federation	Federal State Health Care Institution	Saint-Petersburg
Russian Federation	Medico- Military Academy, Navy Therapy Dept	Saint-Petersburg
Russian Federation	Public Institution of Health City Hospital # 28	Saint-Petersburg
Russian Federation	Saint-Petersburg State Health Institution "Pokrovskaya City Hospital"	Saint-Petersburg
Russian Federation	Federal State Institution	Saratov
Russian Federation	State Educational Institution of High Professional Education Saratov State Medical University	Saratov
Russian Federation	Almasov research institute of Cardiology	St. Petersberg
Russian Federation	Chair and Department of Hospital Therapy	St. Petersburg
Russian Federation	City Hospital #26	St. Petersburg
Russian Federation	City Hospital No 26	St. Petersburg
Russian Federation	Non-state Health Care Institution	St. Petersburg
Russian Federation	Saint-Petersburg Clinical Hospital of RAMS, policlinic department	St. Petersburg
Russian Federation	Saint-Petersburg State Health Care Institution "City Hospital of Saint George the Martyr"	St. Petersburg
Russian Federation	State Institution Saint-Petersburg Dzhanelidze Scientific	St. Petersburg
Russian Federation	State Institition Research Institution of Cardiology of Tomsk	Tomsk
Russian Federation	State Educational institution of Higher Professional Education "Volgograd State Medical University o	Volgograd
Russian Federation	State Health Care Institution "Voronezh Regional Clinical Consultative & Diagnostic Centre"	Voronezh
Russian Federation	City Healthcare Institution Clinical Hospital #8	Yaroslavl
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl
United States	Veterans Affairs Ann Arbor Health Care System	Ann Arbor	Michigan
United States	DCT - APHC, LLC dba Discovery Clinical Trials	Arlington	Texas
United States	Emory University at Grady Health System	Atlanta	Georgia
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	Northside Cardiology Center	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Northeast Cardiology	Bangor	Maine
United States	St. Charles Health System	Bend	Oregon
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Caritas St. Elizabeth's Medical Center	Boston	Massachusetts
United States	Bronx-Lebanon Hospital Center	Bronx	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	Deborah Heart and Lung Center	Browns Mills	New Jersey
United States	Buffalo Heart Group, LLC	Buffalo	New York
United States	Research Foundation State University of New York at Buffalo	Buffalo	New York
United States	Cynthia Thaik	Burbank	California
United States	Capital Area Research	Camp Hill	Pennsylvania
United States	CAMC Health Education and Research Institute	Charleston	West Virginia
United States	VAMC - Charleston, SC	Charleston	South Carolina
United States	Merrimack Valley Cardiology Associates	Chelmsford	Massachusetts
United States	Cardiovascular Associates Ltd.	Chesapeake	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois at Chicago Medical Center	Chicago	Illinois
United States	The Lindner Clinical Trial Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	University Hospitals of Cleveland/Case Western Reserve University	Cleveland	Ohio
United States	Ohio State University Hospital East	Columbus	Ohio
United States	Northeast Medical Center	Concord	North Carolina
United States	Cardiovascular Research Institute of Dallas	Dallas	Texas
United States	Dallas VA Medical Center	Dallas	Texas
United States	U.T. Southwestern Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	VAMC Dayton	Dayton	Ohio
United States	Daytona Heart Group	Daytona Beach	Florida
United States	Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Detroit VA Medical Center	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Durham VA Medical Center	Durham	North Carolina
United States	Compass Medical East Bridgewater	East Bridgewater	Massachusetts
United States	Cardiovascular Research Foundation	Elk Grove Village	Illinois
United States	Cardiovascular Associates of the Delaware Valley	Elmer	New Jersey
United States	Medicor Associates, Inc	Erie	Pennsylvania
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Fresno VA Medical Center	Fresno	California
United States	M & O Clinical Research, LLC	Ft. Lauderdale	Florida
United States	Black Hills VA Health Care System	Ft. Meade	South Dakota
United States	Florida Heart Center	Ft. Pierce	Florida
United States	University of Florida	Gainesville	Florida
United States	CCHS Clinical Research Office/Marymount Hospital	Garfield Heights	Ohio
United States	The Stern Cardiovascular Center	Germantown	Tennessee
United States	Cardiovascular Consultants, Ltd.	Glendale	Arizona
United States	Cardio-Vascular Institute	Greeley	Colorado
United States	Cardiovascular Associates of the Delaware Valley	Haddon Heights	New Jersey
United States	Pentucket Medical Associates	Haverhill	Massachusetts
United States	The Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Leonard J. Chabert Medical Center	Houma	Louisiana
United States	Michael E. DeBakey VA Medical Cntr.	Houston	Texas
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	The Care Group, LLC	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Jamaica Hospital Medical Center	Jamaica	New York
United States	Glacier View Cardiology	Kalispell	Montana
United States	Mid Valley Cardiology	Kingston	New York
United States	Evergreen Healthcare	Kirkland	Washington
United States	Wilford Hall Medical Center	Lackland	Texas
United States	Lancaster Heart and Stroke Foundation	Lancaster	Pennsylvania
United States	Kaiser Permanente	Largo	Maryland
United States	Bryan LGH Heart Institute	Lincoln	Nebraska
United States	NJ Heart	Linden	New Jersey
United States	Central Arkansas Veterans Healthcare System	Little Rock	Arkansas
United States	Heart Clinic Arkansas	Little Rock	Arkansas
United States	CAPRI	Los Angeles	California
United States	Clinica Medica San Miguel	Los Angeles	California
United States	VA Medical Center West Los Angeles	Los Angeles	California
United States	Baptist Healthcare System, Inc. d/b/a Baptist Hospital East	Louisville	Kentucky
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	William S. Middleton Memorial VA Hospital	Madison	Wisconsin
United States	InnovaMed Alliance	Marietta	Georgia
United States	CCHS Clinical Research Office/ Hillcrest Hospital	Mayfield Heights	Ohio
United States	Memphis Heart Clinic	Memphis	Tennessee
United States	Memphis VA Medical Center	Memphis	Tennessee
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Winthrop Cardiology Associates	Mineola	New York
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Cardiovascular Research of Northwest Indiana, LLC	Munster	Indiana
United States	LDS Hospital	Murray	Utah
United States	Vanderbilt Heart and Vascular Institute	Nashville	Tennessee
United States	Charles River Medical Associates	Natick	Massachusetts
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Soundshore Medical Center of Westchester	New Rochelle	New York
United States	NYU School of Medicine	New York	New York
United States	St. Lukes Roosevelt	New York	New York
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	Hawthorn Medical Associates	North Dartmouth	Massachusetts
United States	Northport VA Medical Center	Northport	New York
United States	Mehrdad Kevin Ariani, MD, Inc.	Northridge	California
United States	Texas Tech University Health Sciences Center	Odessa	Texas
United States	COR Clinical Research	Oklahoma City	Oklahoma
United States	Oklahoma City VA Medical Center	Oklahoma City	Oklahoma
United States	Oklahoma Foundation for Cardiovascular Research	Oklahoma City	Oklahoma
United States	Providence St. Peter Hospital	Olympia	Washington
United States	The Creighton Cardiac Center	Omaha	Nebraska
United States	St. Joseph's Regional Medical Center	Paterson	New Jersey
United States	Memorial Hospital Rhode Island	Pawtucket	Rhode Island
United States	Heart, Lung and Vascular Institute	Peoria	Illinois
United States	HeartCare Midwest	Peoria	Illinois
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Eastwick Primary Care	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital- Dept. of Family and Community Health	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Carl T. Hayden VA Medical Center	Phoenix	Arizona
United States	Pittsburgh VA Healthcare System	Pittsburgh	Pennsylvania
United States	Sound Health Research	Port Orchard	Washington
United States	Providence Heart and Vascular Institute	Portland	Oregon
United States	Northwest Hospital	Randallstown	Maryland
United States	The Valley Hospital	Ridgewood	New Jersey
United States	University of Rochester Medical Center	Rochester	New York
United States	Brevard Cardiovascular Research Associates, Inc	Rockledge	Florida
United States	William Beaumont Health Center	Royal Oak	Michigan
United States	UC Davis Medical Center	Sacremento	California
United States	Central Coast Cardiology	Salinas	California
United States	Delmarva Heart Research Foundation	Salisbury	Maryland
United States	University of Utah	Salt Lake City	Utah
United States	Cardiology Clinic of San Antonio	San Antonio	Texas
United States	Naval Medical Center San Diego	San Diego	California
United States	University of Washington	Seattle	Washington
United States	Associates in Cardiology, PA	Silver Spring	Maryland
United States	Lewin, Fagen, and Lown, MD, PC	Smithtown	New York
United States	Electrophysiology Research Foundation	Somerset	New Jersey
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Heartland Regional Medical Clinic	St. Joseph	Missouri
United States	Olive View - UCLA Medial Center	Sylmar	California
United States	SUNY Upstate Medical Center	Syracuse	New York
United States	Syracuse VA Medical Center	Syracuse	New York
United States	Tallahassee Research Institute	Tallahassee	Florida
United States	Community Medical Center	Toms River	New Jersey
United States	Oklahoma Heart Institute	Tulsa	Oklahoma
United States	Tyler Cardiovascular Consultants	Tyler	Texas
United States	Washington DC VA Hospital	Washington	District of Columbia
United States	Washington Hospital Center	Washington	District of Columbia
United States	Howard University Hospital	Washington DC	District of Columbia
United States	Aspirus Heart and Vascular Institute	Wausau	Wisconsin
United States	New Jersey Cardiology Associates	West Orange	New Jersey
United States	The Reading Hospital and Medical Center	West Reading	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Umass Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Georgia,  Russian Federation, 

References & Publications (6)

Desai AS, Lewis EF, Li R, Solomon SD, Assmann SF, Boineau R, Clausell N, Diaz R, Fleg JL, Gordeev I, McKinlay S, O'Meara E, Shaburishvili T, Pitt B, Pfeffer MA. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. 2011 Dec;162(6):966-972.e10. doi: 10.1016/j.ahj.2011.09.007. Epub 2011 Nov 8. — View Citation

Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Heitner JF, Lewis EF, O'Meara E, Rouleau JL, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, McKinlay SM, Pitt B. Regional variat — View Citation

Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM — View Citation

Shah AM, Claggett B, Sweitzer NK, Shah SJ, Anand IS, O'Meara E, Desai AS, Heitner JF, Li G, Fang J, Rouleau J, Zile MR, Markov V, Ryabov V, Reis G, Assmann SF, McKinlay SM, Pitt B, Pfeffer MA, Solomon SD. Cardiac structure and function and prognosis in he — View Citation

Shah AM, Shah SJ, Anand IS, Sweitzer NK, O'Meara E, Heitner JF, Sopko G, Li G, Assmann SF, McKinlay SM, Pitt B, Pfeffer MA, Solomon SD; TOPCAT Investigators. Cardiac structure and function in heart failure with preserved ejection fraction: baseline findin — View Citation

Shah SJ, Heitner JF, Sweitzer NK, Anand IS, Kim HY, Harty B, Boineau R, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Lewis EF, Markov V, O'Meara E, Kobulia B, Shaburishvili T, Solomon SD, Pitt B, Pfeffer MA, Li R. Baseline characteristics of patients — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Outcome of Cardiovascular Mortality, Aborted Cardiac Arrest, or Hospitalization for 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.	No
Secondary	Cardiovascular Mortality		Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Aborted Cardiac Arrest	First incidence of aborted cardiac arrest	Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Hospitalization for the Management of Heart Failure	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.	No
Secondary	All-cause Mortality		Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	Yes
Secondary	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		Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Cardiovascular-related Hospitalization	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.	No
Secondary	Total Hospitalizations (Including Repeat Hospitalizations) for the Management of Heart Failure		Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Composite Outcome of Sudden Death or Aborted Cardiac Arrest, Whichever Occurred First		Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	New Onset Diabetes Mellitus, Among Subjects Without a History of Diabetes Mellitus at Baseline.	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.	No
Secondary	Development of Atrial Fibrillation, Among Subjects Without a History of Atrial Fibrillation at Baseline.	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.	No
Secondary	Myocardial Infarction	First incidence of myocardial infarction	Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Stroke	First incidence of stroke	Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Deterioration of Renal Function	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.	Yes
Secondary	Composite Outcome of Sudden Death, Aborted Cardiac Arrest, or Hospitalization for the Management of Ventricular Tachycardia, Whichever Occurred First		Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.	No
Secondary	Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire.	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.	No
Secondary	Quality of Life, as Measured by the EuroQOL Visual Analog Scale.	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.	No
Secondary	Quality of Life, as Measured by McMaster Overall Treatment Evaluation Questionnaire.	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.	No
Secondary	Depression Symptoms, as Measured by Patient Health Questionnaire.	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.	No
Secondary	Hospitalization for Any Reason	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.	Yes
Secondary	Potassium	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.	Yes
Secondary	Serum Creatinine	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.	Yes
Secondary	Sodium	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.	Yes
Secondary	Chloride	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.	Yes
Secondary	Estimated Glomerular Filtration Rate (GFR)	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.	Yes

External Links

•   Link to PubMed ID #23258572 publication in Circulation: Heart Failure
•   Link to PubMed ID #24249049 publication in Circulation: Heart Failure
•   Link to PubMed ID #24716680 publication in the New England Journal of Medicine
•   Link to PubMed ID #25122186 publication in Circulation: Heart Failure
•   Link to PubMed ID #25406305 publication in Circulation
•   Link to PubMed Identification (ID) #22137068 publication in the American Heart Journal