Clinical trial NCT00094302: Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function
Official title: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Heart Diseases
Heart Failure, Congestive
Keywords: Heart Failure
Diastolic Heart Failure
Preserved Ejection Fraction
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2004-10-15
Enrollment: 3445
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite Outcome of Cardiovascular Mortality, Aborted Cardiac Arrest, or Hospitalization for the Management of Heart Failure, Whichever Occurred First
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Secondary outcomes:
measure: Cardiovascular Mortality
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Aborted Cardiac Arrest
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Hospitalization for the Management of Heart Failure
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: All-cause Mortality
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: 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
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Cardiovascular-related Hospitalization
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Total Hospitalizations (Including Repeat Hospitalizations) for the Management of Heart Failure
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Composite Outcome of Sudden Death or Aborted Cardiac Arrest, Whichever Occurred First
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: New Onset Diabetes Mellitus, Among Subjects Without a History of Diabetes Mellitus at Baseline.
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Development of Atrial Fibrillation, Among Subjects Without a History of Atrial Fibrillation at Baseline.
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Myocardial Infarction
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Stroke
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Deterioration of Renal Function
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Composite Outcome of Sudden Death, Aborted Cardiac Arrest, or Hospitalization for the Management of Ventricular Tachycardia, Whichever Occurred First
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire.
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Quality of Life, as Measured by the EuroQOL Visual Analog Scale.
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Quality of Life, as Measured by McMaster Overall Treatment Evaluation Questionnaire.
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Depression Symptoms, as Measured by Patient Health Questionnaire.
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Hospitalization for Any Reason
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Potassium
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Serum Creatinine
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Sodium
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Chloride
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
measure: Estimated Glomerular Filtration Rate (GFR)
timeFrame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Glendale
country: United States
facility: Cardiovascular Consultants, Ltd.
state: Arizona
city: Phoenix
country: United States
facility: Carl T. Hayden VA Medical Center
state: Arizona
city: Little Rock
country: United States
facility: Central Arkansas Veterans Healthcare System
state: Arkansas
city: Little Rock
country: United States
facility: Heart Clinic Arkansas
state: Arkansas
city: Burbank
country: United States
facility: Cynthia Thaik
state: California
city: Fresno
country: United States
facility: Fresno VA Medical Center
state: California
city: Los Angeles
country: United States
facility: Clinica Medica San Miguel
state: California
city: Los Angeles
country: United States
facility: CAPRI
state: California
city: Los Angeles
country: United States
facility: VA Medical Center West Los Angeles
state: California
city: Northridge
country: United States
facility: Mehrdad Kevin Ariani, MD, Inc.
state: California
city: Sacremento
country: United States
facility: UC Davis Medical Center
state: California
city: Salinas
country: United States
facility: Central Coast Cardiology
state: California
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medial Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Greeley
country: United States
facility: Cardio-Vascular Institute
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Washington DC
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VA Hospital
state: District of Columbia
city: Daytona Beach
country: United States
facility: Daytona Heart Group
state: Florida
city: Ft. Lauderdale
country: United States
facility: M & O Clinical Research, LLC
state: Florida
city: Ft. Pierce
country: United States
facility: Florida Heart Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Rockledge
country: United States
facility: Brevard Cardiovascular Research Associates, Inc
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University at Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Northside Cardiology Center
state: Georgia
city: Marietta
country: United States
facility: InnovaMed Alliance
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Elk Grove Village
country: United States
facility: Cardiovascular Research Foundation
state: Illinois
city: Peoria
country: United States
facility: Heart, Lung and Vascular Institute
state: Illinois
city: Peoria
country: United States
facility: HeartCare Midwest
state: Illinois
city: Indianapolis
country: United States
facility: The Care Group, LLC
state: Indiana
city: Munster
country: United States
facility: Cardiovascular Research of Northwest Indiana, LLC
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Baptist Healthcare System, Inc. d/b/a Baptist Hospital East
state: Kentucky
city: Houma
country: United States
facility: Leonard J. Chabert Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Bangor
country: United States
facility: Northeast Cardiology
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Largo
country: United States
facility: Kaiser Permanente
state: Maryland
city: Randallstown
country: United States
facility: Northwest Hospital
state: Maryland
city: Salisbury
country: United States
facility: Delmarva Heart Research Foundation
state: Maryland
city: Silver Spring
country: United States
facility: Associates in Cardiology, PA
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Caritas St. Elizabeth's Medical Center
state: Massachusetts
city: Chelmsford
country: United States
facility: Merrimack Valley Cardiology Associates
state: Massachusetts
city: East Bridgewater
country: United States
facility: Compass Medical East Bridgewater
state: Massachusetts
city: Haverhill
country: United States
facility: Pentucket Medical Associates
state: Massachusetts
city: Natick
country: United States
facility: Charles River Medical Associates
state: Massachusetts
city: North Dartmouth
country: United States
facility: Hawthorn Medical Associates
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: Umass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Veterans Affairs Ann Arbor Health Care System
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Detroit VA Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Health Center
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Medical Center
state: Minnesota
city: St. Joseph
country: United States
facility: Heartland Regional Medical Clinic
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Cardiology
state: Montana
city: Lincoln
country: United States
facility: Bryan LGH Heart Institute
state: Nebraska
city: Omaha
country: United States
facility: The Creighton Cardiac Center
state: Nebraska
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Elmer
country: United States
facility: Cardiovascular Associates of the Delaware Valley
state: New Jersey
city: Haddon Heights
country: United States
facility: Cardiovascular Associates of the Delaware Valley
state: New Jersey
city: Linden
country: United States
facility: NJ Heart
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Regional Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Somerset
country: United States
facility: Electrophysiology Research Foundation
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
city: West Orange
country: United States
facility: New Jersey Cardiology Associates
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital Center
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: Research Foundation State University of New York at Buffalo
state: New York
city: Buffalo
country: United States
facility: Buffalo Heart Group, LLC
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: Kingston
country: United States
facility: Mid Valley Cardiology
state: New York
city: Mineola
country: United States
facility: Winthrop Cardiology Associates
state: New York
city: New Rochelle
country: United States
facility: Soundshore Medical Center of Westchester
state: New York
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: New York
country: United States
facility: St. Lukes Roosevelt
state: New York
city: Northport
country: United States
facility: Northport VA Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Smithtown
country: United States
facility: Lewin, Fagen, and Lown, MD, PC
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Syracuse
country: United States
facility: Syracuse VA Medical Center
state: New York
city: Concord
country: United States
facility: Northeast Medical Center
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland/Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital East
state: Ohio
city: Dayton
country: United States
facility: VAMC Dayton
state: Ohio
city: Garfield Heights
country: United States
facility: CCHS Clinical Research Office/Marymount Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: CCHS Clinical Research Office/ Hillcrest Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma City VA Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Cardiovascular Research
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Bend
country: United States
facility: St. Charles Health System
state: Oregon
city: Portland
country: United States
facility: Providence Heart and Vascular Institute
state: Oregon
city: Camp Hill
country: United States
facility: Capital Area Research
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Erie
country: United States
facility: Medicor Associates, Inc
state: Pennsylvania
city: Hershey
country: United States
facility: The Milton S. Hershey Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster Heart and Stroke Foundation
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital- Dept. of Family and Community Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Eastwick Primary Care
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pittsburgh VA Healthcare System
state: Pennsylvania
city: West Reading
country: United States
facility: The Reading Hospital and Medical Center
state: Pennsylvania
city: Pawtucket
country: United States
facility: Memorial Hospital Rhode Island
state: Rhode Island
city: Charleston
country: United States
facility: VAMC - Charleston, SC
state: South Carolina
city: Ft. Meade
country: United States
facility: Black Hills VA Health Care System
state: South Dakota
city: Germantown
country: United States
facility: The Stern Cardiovascular Center
state: Tennessee
city: Memphis
country: United States
facility: Memphis VA Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Memphis Heart Clinic
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Heart and Vascular Institute
state: Tennessee
city: Arlington
country: United States
facility: DCT - APHC, LLC dba Discovery Clinical Trials
state: Texas
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Dallas
country: United States
facility: Cardiovascular Research Institute of Dallas
state: Texas
city: Dallas
country: United States
facility: U.T. Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Cntr.
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Lackland
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: Odessa
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: San Antonio
country: United States
facility: Cardiology Clinic of San Antonio
state: Texas
city: Tyler
country: United States
facility: Tyler Cardiovascular Consultants
state: Texas
city: Murray
country: United States
facility: LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Chesapeake
country: United States
facility: Cardiovascular Associates Ltd.
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Kirkland
country: United States
facility: Evergreen Healthcare
state: Washington
city: Olympia
country: United States
facility: Providence St. Peter Hospital
state: Washington
city: Port Orchard
country: United States
facility: Sound Health Research
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Charleston
country: United States
facility: CAMC Health Education and Research Institute
state: West Virginia
city: Madison
country: United States
facility: William S. Middleton Memorial VA Hospital
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Heart and Vascular Institute
state: Wisconsin
city: Bahia Blanca
country: Argentina
facility: Instituto de Investigaciones Clinicas de Bahia Blanca
state: Buenos Aires
city: Coronel Suarez
country: Argentina
facility: Clinica Coronel Suarez
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas de Mar Del Plata
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas de Quilmes
state: Buenos Aires
city: Cipolletti
country: Argentina
facility: Policlinico Modelo de Cipoletti
state: Rio Negro
city: Buenos Aires
country: Argentina
facility: IMAI Research
city: Buenos Aires
country: Argentina
facility: CIPREC
city: Buenos Aires
country: Argentina
facility: Instituto Cardiologico Ezpecializado S.R.L
city: Buenos Aires
country: Argentina
facility: Clinica IMA
city: Cordoba
country: Argentina
facility: Clinica Privada Del Prado
city: Rosario Santa Fe
country: Argentina
facility: Instituto de Investigaciones Clinicas de Rosario
city: Salta
country: Argentina
facility: Hospital San Bernardo
city: Santa Fe
country: Argentina
facility: Centro de Investigaciones Clinicas del Litoral SRL
city: Santa Fe
country: Argentina
facility: Sanatorio Mayo S.A.
city: Tucuman
country: Argentina
facility: Centro Privado de Cardiologia
city: Tucuman
country: Argentina
facility: Centro Modelo de Cardiología
city: Tucuman
country: Argentina
facility: Instituto de Cardiologia SRL
city: Belo Horizonte
country: Brazil
facility: Hospital Felicio Rocho
city: Belo Horizonte
country: Brazil
facility: Santa Casa De Belo Horizonte
city: Campinas
country: Brazil
facility: HMCP PUC Campinas
city: Curitiba Parana
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Curitiba
city: Goias
country: Brazil
facility: Hospital das Clinicas da Universidade Federal de Goias
city: Marilia Sao Paulo
country: Brazil
facility: Instituto do Coracao de Marilia
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo
city: Pernambuco
country: Brazil
facility: PROCAPE
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital Mae De Deus
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Pedro Ernesto
city: Rio de Janeiro
country: Brazil
facility: Santa Casa de Misericordia do Rio de Janeiro
city: San Paulo
country: Brazil
facility: Instituto de Molestias Cardiosvaculares
city: Santa Catarina
country: Brazil
facility: Instituto de Cardiologia de Santa Catarina
city: Sao Paulo
country: Brazil
facility: Incor Fmusp
city: Sao Paulo
country: Brazil
facility: UNIFESP/Hospital Sao Paulo
city: Uberlandia
country: Brazil
facility: Instituto do Coracao do Triangulo Mineiro
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: New Westminster
country: Canada
facility: Fraser Clinical Trials Inc.
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: St. John's
country: Canada
facility: Health Science Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Capital District Health Authority
state: Nova Scotia
city: Cambridge
country: Canada
facility: Dr. Saul Vizel Cardiac Research Office
state: Ontario
city: Cornwall
country: Canada
facility: Cornwall Clinical Trials
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - General Site
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Sudbury
country: Canada
facility: Dr. Gurcharan Syan (PP)
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS - Hopital Fleurimont
state: Quebec
city: Granby
country: Canada
facility: Service de la Recherche
state: Quebec
city: Laval
country: Canada
facility: Cite de la Sante de Laval
state: Quebec
city: Levis
country: Canada
facility: Clinique Cardiologie Levis
state: Quebec
city: Montreal
country: Canada
facility: Hopital Du Sacre Coeur de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hotel Dieu
state: Quebec
city: Montreal
country: Canada
facility: Chum Hotel Dieu
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Centre de recherche clinique de Quebec
state: Quebec
city: Sainte Charles Borromee
country: Canada
facility: Centre Hosp Regional de Lanaudiere
state: Quebec
city: St. George
country: Canada
facility: C.S.S.S.B.
state: Quebec
city: Ste-Foy
country: Canada
facility: Hopital Laval
state: Quebec
city: Terrebonne
country: Canada
facility: CSSS du Sud de Lanaudiere (Hopital Pierre-Le Gardeur)
state: Quebec
city: Thetford-Mines
country: Canada
facility: Centre De Sante et De Services Sociaux De Thetford
state: Quebec
city: Edmonton
country: Canada
facility: Misericordia Hospital - Cardiac Sciences
city: Longueuil
country: Canada
facility: CDRC Rive-Sud
city: Montreal
country: Canada
facility: SMBD Jewish General Hospital
city: Saskatoon
country: Canada
facility: Saskatchewan Heart Centre
city: Surrey
country: Canada
facility: Cardiology Clinical Trials - Surrey Memorial Hospital
city: Trois Rivieres
country: Canada
facility: Centre Hospitalier de Trois-Rivieres
city: Kutaisi
country: Georgia
facility: L &J Clinic
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University Clinic #1
city: Tbilisi
country: Georgia
facility: Cardio-Reanimation Centre
city: Tbilisi
country: Georgia
facility: Multiprofile Clinical Hospital of Tbilisi #2
city: Tbilisi
country: Georgia
facility: Emergency Cardiology Centre
city: Tbilisi
country: Georgia
facility: National Center of Therapy
city: Tbilisi
country: Georgia
facility: Diagnostic Services Clinic
city: Tbilisi
country: Georgia
facility: Clinic of Angiocardiology "ADAPTI"
city: Tibilisi
country: Georgia
facility: Cardiology Clinic
city: Gatchina
country: Russian Federation
facility: Municipal Healthcare Institution <>
state: Leningrad Region
city: Barnaul
country: Russian Federation
facility: Altay State Medical University of federal agency of public health and social progress RF
city: Barnaul
country: Russian Federation
facility: Municipal Health Care Institution "City Hospital #1"
city: Kaliningrad
country: Russian Federation
facility: Kaliningrad Region Hospital
city: Kemerovo
country: Russian Federation
facility: Kemerovo Cadiologiy Dispensary, Kemerovo Medical Academy
city: Kemerovo
country: Russian Federation
facility: Nonstate Healthcare Institution
city: Krasnodar
country: Russian Federation
facility: State Healthcare Institution "Region Clinical Hospital #1
city: Moscow
country: Russian Federation
facility: National Research Center for Preventitive Medicine
city: Moscow
country: Russian Federation
facility: Russian State Medical University, Hospital Therapy Department #1
city: Moscow
country: Russian Federation
facility: State Education High Professional Education Russian State Medical University
city: Moscow
country: Russian Federation
facility: Federal State Institution "Outpatient clinic #3 of President's Management Department of Russian Fede
city: Moscow
country: Russian Federation
facility: Research Institute of Physico-Chemical Medicine Center for Atheosclerosis and Laboratory
city: Moscow
country: Russian Federation
facility: Non State Health Care Institution Central Hospital #6 of Russian Railways JSC
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk Municipal Clinical Emergency Hosp. # 2
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution "City Alexander's Hospital"
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Institution of Health Protection, "City Hosptial # 15"
city: Saint Petersburg
country: Russian Federation
facility: Chair of Nephrology and Dialysis of St Petersburg State Medical University
city: Saint-Petersburg
country: Russian Federation
facility: Public Institution of Health City Hospital # 28
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Health Care Institution
city: Saint-Petersburg
country: Russian Federation
facility: Medico- Military Academy, Navy Therapy Dept
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Health Institution "Pokrovskaya City Hospital"
city: Saratov
country: Russian Federation
facility: Federal State Institution
city: Saratov
country: Russian Federation
facility: State Educational Institution of High Professional Education Saratov State Medical University
city: St. Petersberg
country: Russian Federation
facility: Almasov research institute of Cardiology
city: St. Petersburg
country: Russian Federation
facility: State Institution Saint-Petersburg Dzhanelidze Scientific
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg Clinical Hospital of RAMS, policlinic department
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Health Care Institution "City Hospital of Saint George the Martyr"
city: St. Petersburg
country: Russian Federation
facility: Non-state Health Care Institution
city: St. Petersburg
country: Russian Federation
facility: City Hospital #26
city: St. Petersburg
country: Russian Federation
facility: City Hospital No 26
city: St. Petersburg
country: Russian Federation
facility: Chair and Department of Hospital Therapy
city: Tomsk
country: Russian Federation
facility: State Institition Research Institution of Cardiology of Tomsk
city: Volgograd
country: Russian Federation
facility: State Educational institution of Higher Professional Education "Volgograd State Medical University o
city: Voronezh
country: Russian Federation
facility: State Health Care Institution "Voronezh Regional Clinical Consultative & Diagnostic Centre"
city: Yaroslavl
country: Russian Federation
facility: City Healthcare Institution Clinical Hospital #8
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
Study officials:
affiliation: New England Research Institutes, Inc.
name: Sonja M. McKinlay, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Myhre PL, Vaduganathan M, O'Meara E, Claggett BL, de Denus S, Jarolim P, Anand IS, Pitt B, Rouleau JL, Solomon SD, Pfeffer MA, Desai AS. Mechanistic Effects of Spironolactone on Cardiovascular and Renal Biomarkers in Heart Failure With Preserved Ejection Fraction: A TOPCAT Biorepository Study. Circ Heart Fail. 2020 Jan;13(1):e006638. doi: 10.1161/CIRCHEARTFAILURE.119.006638. Epub 2020 Jan 20.
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citation: Tromp J, Shen L, Jhund PS, Anand IS, Carson PE, Desai AS, Granger CB, Komajda M, McKelvie RS, Pfeffer MA, Solomon SD, Kober L, Swedberg K, Zile MR, Pitt B, Lam CSP, McMurray JJV. Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2019 Aug 6;74(5):601-612. doi: 10.1016/j.jacc.2019.05.052.
citation: Beale AL, Nanayakkara S, Kaye DM. Impact of Sex on Ventricular-Vascular Stiffness and Long-Term Outcomes in Heart Failure With Preserved Ejection Fraction: TOPCAT Trial Substudy. J Am Heart Assoc. 2019 Jul 2;8(13):e012190. doi: 10.1161/JAHA.119.012190. Epub 2019 Jun 22.
citation: Selvaraj S, Claggett B, Shah SJ, Anand IS, Rouleau JL, Desai AS, Lewis EF, Vaduganathan M, Wang SY, Pitt B, Sweitzer NK, Pfeffer MA, Solomon SD. Utility of the Cardiovascular Physical Examination and Impact of Spironolactone in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2019 Jul;12(7):e006125. doi: 10.1161/CIRCHEARTFAILURE.119.006125. Epub 2019 Jun 21.
citation: Neefs J, van den Berg NWE, Krul SPJ, Boekholdt SM, de Groot JR. Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial. Am J Cardiovasc Drugs. 2020 Feb;20(1):73-80. doi: 10.1007/s40256-019-00353-5.
citation: Kristensen SL, Mogensen UM, Jhund PS, Rorth R, Anand IS, Carson PE, Desai AS, Pitt B, Pfeffer MA, Solomon SD, Zile MR, Kober L, McMurray JJV. N-Terminal Pro-B-Type Natriuretic Peptide Levels for Risk Prediction in Patients With Heart Failure and Preserved Ejection Fraction According to Atrial Fibrillation Status. Circ Heart Fail. 2019 Mar;12(3):e005766. doi: 10.1161/CIRCHEARTFAILURE.118.005766.
citation: Merrill M, Sweitzer NK, Lindenfeld J, Kao DP. Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial. JACC Heart Fail. 2019 Mar;7(3):228-238. doi: 10.1016/j.jchf.2019.01.003.
citation: Myhre PL, O'Meara E, Claggett BL, de Denus S, Jarolim P, Anand IS, Beldhuis IE, Fleg JL, Lewis E, Pitt B, Rouleau JL, Solomon SD, Pfeffer MA, Desai AS. Cardiac Troponin I and Risk of Cardiac Events in Patients With Heart Failure and Preserved Ejection Fraction. Circ Heart Fail. 2018 Nov;11(11):e005312. doi: 10.1161/CIRCHEARTFAILURE.118.005312.
citation: Selvaraj S, Claggett B, Shah SJ, Anand I, Rouleau JL, O'Meara E, Desai AS, Lewis EF, Pitt B, Sweitzer NK, Fang JC, Pfeffer MA, Solomon SD. Prognostic Value of Albuminuria and Influence of Spironolactone in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2018 Nov;11(11):e005288. doi: 10.1161/CIRCHEARTFAILURE.118.005288.
citation: Myhre PL, Vaduganathan M, Claggett BL, Anand IS, Sweitzer NK, Fang JC, O'Meara E, Shah SJ, Desai AS, Lewis EF, Rouleau J, Pitt B, Pfeffer MA, Solomon SD. Association of Natriuretic Peptides With Cardiovascular Prognosis in Heart Failure With Preserved Ejection Fraction: Secondary Analysis of the TOPCAT Randomized Clinical Trial. JAMA Cardiol. 2018 Oct 1;3(10):1000-1005. doi: 10.1001/jamacardio.2018.2568.
citation: Cikes M, Claggett B, Shah AM, Desai AS, Lewis EF, Shah SJ, Anand IS, O'Meara E, Rouleau JL, Sweitzer NK, Fang JC, Saksena S, Pitt B, Pfeffer MA, Solomon SD. Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial. JACC Heart Fail. 2018 Aug;6(8):689-697. doi: 10.1016/j.jchf.2018.05.005. Epub 2018 Jul 11.
citation: Lewis EF, Claggett B, Shah AM, Liu J, Shah SJ, Anand I, O'Meara E, Sweitzer NK, Rouleau JL, Fang JC, Desai AS, Retta TM, Solomon SD, Heitner JF, Stamos TD, Boineau R, Pitt B, Pfeffer MA. Racial Differences in Characteristics and Outcomes of Patients With Heart Failure and Preserved Ejection Fraction in the Treatment of Preserved Cardiac Function Heart Failure Trial. Circ Heart Fail. 2018 Mar;11(3):e004457. doi: 10.1161/CIRCHEARTFAILURE.117.004457.
citation: Vaduganathan M, Claggett BL, Chatterjee NA, Anand IS, Sweitzer NK, Fang JC, O'Meara E, Shah SJ, Hegde SM, Desai AS, Lewis EF, Rouleau J, Pitt B, Pfeffer MA, Solomon SD. Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial. JACC Heart Fail. 2018 Aug;6(8):653-661. doi: 10.1016/j.jchf.2018.02.014. Epub 2018 Mar 4.
citation: Rossignol P, Claggett BL, Liu J, Vardeny O, Pitt B, Zannad F, Solomon S. Spironolactone and Resistant Hypertension in Heart Failure With Preserved Ejection Fraction. Am J Hypertens. 2018 Mar 10;31(4):407-414. doi: 10.1093/ajh/hpx210.
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