Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function
- Conditions
- Heart DiseasesHeart Failure, CongestiveCardiovascular Diseases
- Interventions
- Drug: PlaceboDrug: Spironolactone
- Registration Number
- NCT00094302
- Lead Sponsor
- Carelon Research
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3445
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo of spironolactone Spironolactone 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.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Cardiovascular Mortality 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 Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. Deterioration of Renal Function 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.)
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. Aborted Cardiac Arrest Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. First incidence of aborted cardiac arrest
All-cause Mortality 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 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 Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. Hospitalization for Any Reason 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
Serum Creatinine 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.
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. First incidence of a hospitalization for the management of heart failure
Myocardial Infarction Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. First incidence of myocardial infarction
Quality of Life, as Measured by the EuroQOL Visual Analog Scale. 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.Quality of Life, as Measured by McMaster Overall Treatment Evaluation Questionnaire. 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.Potassium 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.
Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire. 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.Depression Symptoms, as Measured by Patient Health Questionnaire. 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.Sodium 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.
Estimated Glomerular Filtration Rate (GFR) 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.
Cardiovascular-related Hospitalization 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
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. First incidence of new onset diabetes mellitus among subjects without a history of diabetes mellitus at baseline.
Development 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. First incidence of atrial fibrillation among subjects without a history of atrial fibrillation at baseline
Stroke Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. First incidence of stroke
Chloride 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.
Trial Locations
- Locations (269)
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Cardiovascular Research Institute of Dallas
🇺🇸Dallas, Texas, United States
Aspirus Heart and Vascular Institute
🇺🇸Wausau, Wisconsin, United States
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Morehouse School of Medicine
🇺🇸Atlanta, Georgia, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
University Hospitals of Cleveland/Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Ohio State University Hospital East
🇺🇸Columbus, Ohio, United States
Michael E. DeBakey VA Medical Cntr.
🇺🇸Houston, Texas, United States
The Methodist Hospital Research Institute
🇺🇸Houston, Texas, United States
LDS Hospital
🇺🇸Murray, Utah, United States
Santa Casa de Misericordia do Rio de Janeiro
🇧🇷Rio de Janeiro, Brazil
Instituto de Cardiologia de Santa Catarina
🇧🇷Santa Catarina, Brazil
Clinique Cardiologie Levis
🇨🇦Levis, Quebec, Canada
Hopital Du Sacre Coeur de Montreal
🇨🇦Montreal, Quebec, Canada
CHUM - Hotel Dieu
🇨🇦Montreal, Quebec, Canada
Chair of Nephrology and Dialysis of St Petersburg State Medical University
🇷🇺Saint Petersburg, Russian Federation
The Care Group, LLC
🇺🇸Indianapolis, Indiana, United States
Minneapolis VA Medical Center
🇺🇸Minneapolis, Minnesota, United States
Cardiology Clinic of San Antonio
🇺🇸San Antonio, Texas, United States
Clinica IMA
🇦🇷Buenos Aires, Argentina
Clinica Privada Del Prado
🇦🇷Cordoba, Argentina
PROCAPE
🇧🇷Pernambuco, Brazil
Vanderbilt Heart and Vascular Institute
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
St. Boniface General Hospital
🇨🇦Winnipeg, Manitoba, Canada
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Detroit VA Medical Center
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Central Arkansas Veterans Healthcare System
🇺🇸Little Rock, Arkansas, United States
Heart Clinic Arkansas
🇺🇸Little Rock, Arkansas, United States
Cardiovascular Consultants, Ltd.
🇺🇸Glendale, Arizona, United States
Washington DC VA Hospital
🇺🇸Washington, District of Columbia, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Memphis Heart Clinic
🇺🇸Memphis, Tennessee, United States
Deborah Heart and Lung Center
🇺🇸Browns Mills, New Jersey, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
The Stern Cardiovascular Center
🇺🇸Germantown, Tennessee, United States
Bryan LGH Heart Institute
🇺🇸Lincoln, Nebraska, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
NJ Heart
🇺🇸Linden, New Jersey, United States
Sanatorio Mayo S.A.
🇦🇷Santa Fe, Argentina
Instituto de Cardiologia SRL
🇦🇷Tucuman, Argentina
CHUS - Hopital Fleurimont
🇨🇦Fleurimont, Quebec, Canada
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Glacier View Cardiology
🇺🇸Kalispell, Montana, United States
St. Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
The Valley Hospital
🇺🇸Ridgewood, New Jersey, United States
Memphis VA Medical Center
🇺🇸Memphis, Tennessee, United States
Cardiovascular Associates of the Delaware Valley
🇺🇸Haddon Heights, New Jersey, United States
CAMC Health Education and Research Institute
🇺🇸Charleston, West Virginia, United States
University of Tennessee Health Science Center
🇺🇸Memphis, Tennessee, United States
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
Centro de Investigaciones Clinicas del Litoral SRL
🇦🇷Santa Fe, Argentina
Centro Modelo de Cardiología
🇦🇷Tucuman, Argentina
Instituto de Investigaciones Clinicas de Bahia Blanca
🇦🇷Bahia Blanca, Buenos Aires, Argentina
Fraser Clinical Trials Inc.
🇨🇦New Westminster, British Columbia, Canada
University of Washington
🇺🇸Seattle, Washington, United States
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Kaliningrad Region Hospital
🇷🇺Kaliningrad, Russian Federation
Instituto de Investigaciones Clinicas de Quilmes
🇦🇷Quilmes, Buenos Aires, Argentina
IMAI Research
🇦🇷Buenos Aires, Argentina
CIPREC
🇦🇷Buenos Aires, Argentina
Montreal General Hospital
🇨🇦Montreal, Quebec, Canada
Centre Hosp Regional de Lanaudiere
🇨🇦Sainte Charles Borromee, Quebec, Canada
Cardiology Clinic
🇬🇪Tibilisi, Georgia
Municipal Health Care Institution "City Hospital #1"
🇷🇺Barnaul, Russian Federation
Saint-Petersburg State Healthcare Institution "City Alexander's Hospital"
🇷🇺Saint Petersburg, Russian Federation
Capital District Health Authority
🇨🇦Halifax, Nova Scotia, Canada
Health Science Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Hospital Italiano de La Plata
🇦🇷La Plata, Buenos Aires, Argentina
Policlinico Modelo de Cipoletti
🇦🇷Cipolletti, Rio Negro, Argentina
University of Calgary
🇨🇦Calgary, Alberta, Canada
Cite de la Sante de Laval
🇨🇦Laval, Quebec, Canada
Hopital Laval
🇨🇦Ste-Foy, Quebec, Canada
Tbilisi State Medical University Clinic #1
🇬🇪Tbilisi, Georgia
Multiprofile Clinical Hospital of Tbilisi #2
🇬🇪Tbilisi, Georgia
Diagnostic Services Clinic
🇬🇪Tbilisi, Georgia
Medico- Military Academy, Navy Therapy Dept
🇷🇺Saint-Petersburg, Russian Federation
Saint-Petersburg State Health Care Institution "City Hospital of Saint George the Martyr"
🇷🇺St. Petersburg, Russian Federation
City Hospital #26
🇷🇺St. Petersburg, 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
State Education High Professional Education Russian State Medical University
🇷🇺Moscow, Russian Federation
Centre de recherche clinique de Quebec
🇨🇦Quebec City, Quebec, Canada
C.S.S.S.B.
🇨🇦St. George, Quebec, Canada
Municipal Healthcare Institution <>
🇷🇺Gatchina, Leningrad Region, Russian Federation
Kemerovo Cadiologiy Dispensary, Kemerovo Medical Academy
🇷🇺Kemerovo, Russian Federation
Nonstate Healthcare Institution
🇷🇺Kemerovo, Russian Federation
State Institution Saint-Petersburg Dzhanelidze Scientific
🇷🇺St. Petersburg, Russian Federation
Centre De Sante et De Services Sociaux De Thetford
🇨🇦Thetford-Mines, Quebec, Canada
Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
Saint-Petersburg State Institution of Health Protection, "City Hosptial # 15"
🇷🇺Saint Petersburg, Russian Federation
Federal State Health Care Institution
🇷🇺Saint-Petersburg, Russian Federation
Non-state Health Care Institution
🇷🇺St. Petersburg, Russian Federation
City Hospital No 26
🇷🇺St. Petersburg, Russian Federation
Saint-Petersburg Clinical Hospital of RAMS, policlinic department
🇷🇺St. Petersburg, Russian Federation
Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, Brazil
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
The Creighton Cardiac Center
🇺🇸Omaha, Nebraska, United States
L &J Clinic
🇬🇪Kutaisi, Georgia
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Carl T. Hayden VA Medical Center
🇺🇸Phoenix, Arizona, United States
Cynthia Thaik
🇺🇸Burbank, California, United States
Fresno VA Medical Center
🇺🇸Fresno, California, United States
Clinica Medica San Miguel
🇺🇸Los Angeles, California, United States
CAPRI
🇺🇸Los Angeles, California, United States
VA Medical Center West Los Angeles
🇺🇸Los Angeles, California, United States
Mehrdad Kevin Ariani, MD, Inc.
🇺🇸Northridge, California, United States
UC Davis Medical Center
🇺🇸Sacremento, California, United States
Central Coast Cardiology
🇺🇸Salinas, California, United States
Naval Medical Center San Diego
🇺🇸San Diego, California, United States
Olive View - UCLA Medial Center
🇺🇸Sylmar, California, United States
Cardio-Vascular Institute
🇺🇸Greeley, Colorado, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Howard University Hospital
🇺🇸Washington DC, District of Columbia, United States
M & O Clinical Research, LLC
🇺🇸Ft. Lauderdale, Florida, United States
Daytona Heart Group
🇺🇸Daytona Beach, Florida, United States
Florida Heart Center
🇺🇸Ft. Pierce, Florida, United States
Emory University at Grady Health System
🇺🇸Atlanta, Georgia, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Tallahassee Research Institute
🇺🇸Tallahassee, Florida, United States
Northside Cardiology Center
🇺🇸Atlanta, Georgia, United States
InnovaMed Alliance
🇺🇸Marietta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Heart, Lung and Vascular Institute
🇺🇸Peoria, Illinois, United States
HeartCare Midwest
🇺🇸Peoria, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Cardiovascular Research Foundation
🇺🇸Elk Grove Village, Illinois, United States
University of Illinois at Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Cardiovascular Research of Northwest Indiana, LLC
🇺🇸Munster, Indiana, United States
Baptist Healthcare System, Inc. d/b/a Baptist Hospital East
🇺🇸Louisville, Kentucky, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Leonard J. Chabert Medical Center
🇺🇸Houma, Louisiana, United States
Northeast Cardiology
🇺🇸Bangor, Maine, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Kaiser Permanente
🇺🇸Largo, Maryland, United States
Delmarva Heart Research Foundation
🇺🇸Salisbury, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Caritas St. Elizabeth's Medical Center
🇺🇸Boston, Massachusetts, United States
Merrimack Valley Cardiology Associates
🇺🇸Chelmsford, Massachusetts, United States
Pentucket Medical Associates
🇺🇸Haverhill, Massachusetts, United States
Compass Medical East Bridgewater
🇺🇸East Bridgewater, Massachusetts, United States
Charles River Medical Associates
🇺🇸Natick, Massachusetts, United States
Hawthorn Medical Associates
🇺🇸North Dartmouth, Massachusetts, United States
Umass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Veterans Affairs Ann Arbor Health Care System
🇺🇸Ann Arbor, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Heartland Regional Medical Clinic
🇺🇸St. Joseph, Missouri, United States
Electrophysiology Research Foundation
🇺🇸Somerset, New Jersey, United States
Community Medical Center
🇺🇸Toms River, New Jersey, United States
New Jersey Cardiology Associates
🇺🇸West Orange, New Jersey, United States
Bronx-Lebanon Hospital Center
🇺🇸Bronx, New York, United States
Research Foundation State University of New York at Buffalo
🇺🇸Buffalo, New York, United States
Buffalo Heart Group, LLC
🇺🇸Buffalo, New York, United States
Mid Valley Cardiology
🇺🇸Kingston, New York, United States
Winthrop Cardiology Associates
🇺🇸Mineola, New York, United States
NYU School of Medicine
🇺🇸New York, New York, United States
Soundshore Medical Center of Westchester
🇺🇸New Rochelle, New York, United States
St. Lukes Roosevelt
🇺🇸New York, New York, United States
Northport VA Medical Center
🇺🇸Northport, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
SUNY Upstate Medical Center
🇺🇸Syracuse, New York, United States
Syracuse VA Medical Center
🇺🇸Syracuse, New York, United States
Northeast Medical Center
🇺🇸Concord, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
The Lindner Clinical Trial Center
🇺🇸Cincinnati, Ohio, United States
VAMC Dayton
🇺🇸Dayton, Ohio, United States
COR Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
CCHS Clinical Research Office/ Hillcrest Hospital
🇺🇸Mayfield Heights, Ohio, United States
Oklahoma City VA Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Foundation for Cardiovascular Research
🇺🇸Oklahoma City, Oklahoma, United States
CCHS Clinical Research Office/Marymount Hospital
🇺🇸Garfield Heights, Ohio, United States
St. Charles Health System
🇺🇸Bend, Oregon, United States
Capital Area Research
🇺🇸Camp Hill, Pennsylvania, United States
Providence Heart and Vascular Institute
🇺🇸Portland, Oregon, United States
Medicor Associates, Inc
🇺🇸Erie, Pennsylvania, United States
The Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Lancaster Heart and Stroke Foundation
🇺🇸Lancaster, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital- Dept. of Family and Community Health
🇺🇸Philadelphia, Pennsylvania, United States
Eastwick Primary Care
🇺🇸Philadelphia, Pennsylvania, United States
Pittsburgh VA Healthcare System
🇺🇸Pittsburgh, Pennsylvania, United States
The Reading Hospital and Medical Center
🇺🇸West Reading, Pennsylvania, United States
Memorial Hospital Rhode Island
🇺🇸Pawtucket, Rhode Island, United States
VAMC - Charleston, SC
🇺🇸Charleston, South Carolina, United States
Black Hills VA Health Care System
🇺🇸Ft. Meade, South Dakota, United States
DCT - APHC, LLC dba Discovery Clinical Trials
🇺🇸Arlington, Texas, United States
U.T. Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Wilford Hall Medical Center
🇺🇸Lackland, Texas, United States
Tyler Cardiovascular Consultants
🇺🇸Tyler, Texas, United States
Texas Tech University Health Sciences Center
🇺🇸Odessa, Texas, United States
Sentara Cardiovascular Research Institute
🇺🇸Norfolk, Virginia, United States
Cardiovascular Associates Ltd.
🇺🇸Chesapeake, Virginia, United States
Evergreen Healthcare
🇺🇸Kirkland, Washington, United States
Providence St. Peter Hospital
🇺🇸Olympia, Washington, United States
Sound Health Research
🇺🇸Port Orchard, Washington, United States
William S. Middleton Memorial VA Hospital
🇺🇸Madison, Wisconsin, United States
Instituto de Investigaciones Clinicas de Mar Del Plata
🇦🇷Mar del Plata, Buenos Aires, Argentina
Clinica Coronel Suarez
🇦🇷Coronel Suarez, Buenos Aires, Argentina
Instituto Cardiologico Ezpecializado S.R.L
🇦🇷Buenos Aires, Argentina
Instituto de Investigaciones Clinicas de Rosario
🇦🇷Rosario Santa Fe, Argentina
Hospital San Bernardo
🇦🇷Salta, Argentina
Centro Privado de Cardiologia
🇦🇷Tucuman, Argentina
Santa Casa De Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Hospital Felicio Rocho
🇧🇷Belo Horizonte, Brazil
Irmandade da Santa Casa de Misericordia de Curitiba
🇧🇷Curitiba Parana, Brazil
Instituto do Coracao de Marilia
🇧🇷Marilia Sao Paulo, Brazil
HMCP PUC Campinas
🇧🇷Campinas, Brazil
Hospital das Clinicas da Universidade Federal de Goias
🇧🇷Goias, 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
Incor Fmusp
🇧🇷Sao Paulo, Brazil
Instituto de Molestias Cardiosvaculares
🇧🇷San Paulo, Brazil
Instituto do Coracao do Triangulo Mineiro
🇧🇷Uberlandia, Brazil
UNIFESP/Hospital Sao Paulo
🇧🇷Sao Paulo, Brazil
Dr. Saul Vizel Cardiac Research Office
🇨🇦Cambridge, Ontario, Canada
Cornwall Clinical Trials
🇨🇦Cornwall, Ontario, Canada
Dr. Gurcharan Syan (PP)
🇨🇦Sudbury, Ontario, Canada
Hamilton Health Sciences - General Site
🇨🇦Hamilton, Ontario, Canada
London Health Sciences Center
🇨🇦London, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
Service de la Recherche
🇨🇦Granby, Quebec, Canada
Chum Hotel Dieu
🇨🇦Montreal, Quebec, Canada
CSSS du Sud de Lanaudiere (Hopital Pierre-Le Gardeur)
🇨🇦Terrebonne, Quebec, Canada
Misericordia Hospital - Cardiac Sciences
🇨🇦Edmonton, Canada
CDRC Rive-Sud
🇨🇦Longueuil, Canada
Saskatchewan Heart Centre
🇨🇦Saskatoon, Canada
Cardiology Clinical Trials - Surrey Memorial Hospital
🇨🇦Surrey, Canada
SMBD Jewish General Hospital
🇨🇦Montreal, Canada
Centre Hospitalier de Trois-Rivieres
🇨🇦Trois Rivieres, Canada
Cardio-Reanimation Centre
🇬🇪Tbilisi, Georgia
National Center of Therapy
🇬🇪Tbilisi, Georgia
Emergency Cardiology Centre
🇬🇪Tbilisi, Georgia
Clinic of Angiocardiology "ADAPTI"
🇬🇪Tbilisi, Georgia
Altay State Medical University of federal agency of public health and social progress RF
🇷🇺Barnaul, Russian Federation
State Healthcare Institution "Region Clinical Hospital #1
🇷🇺Krasnodar, 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
Federal State Institution "Outpatient clinic #3 of President's Management Department of Russian Fede
🇷🇺Moscow, Russian Federation
Novosibirsk Municipal Clinical Emergency Hosp. # 2
🇷🇺Novosibirsk, 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
State Educational Institution of High Professional Education Saratov State Medical University
🇷🇺Saratov, Russian Federation
Federal State Institution
🇷🇺Saratov, Russian Federation
Almasov research institute of Cardiology
🇷🇺St. Petersberg, Russian Federation
Chair and Department of Hospital Therapy
🇷🇺St. Petersburg, Russian Federation
State Health Care Institution "Voronezh Regional Clinical Consultative & Diagnostic Centre"
🇷🇺Voronezh, Russian Federation
Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
City Healthcare Institution Clinical Hospital #8
🇷🇺Yaroslavl, 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
Northwest Hospital
🇺🇸Randallstown, Maryland, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
William Beaumont Health Center
🇺🇸Royal Oak, Michigan, United States
New York Methodist Hospital
🇺🇸Brooklyn, New York, United States
Lewin, Fagen, and Lown, MD, PC
🇺🇸Smithtown, New York, United States
Oklahoma Heart Institute
🇺🇸Tulsa, Oklahoma, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
Dallas VA Medical Center
🇺🇸Dallas, Texas, United States
Associates in Cardiology, PA
🇺🇸Silver Spring, Maryland, United States
Jamaica Hospital Medical Center
🇺🇸Jamaica, New York, United States
Brevard Cardiovascular Research Associates, Inc
🇺🇸Rockledge, Florida, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States