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NCT02901184PHASE3Recruiting

Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction

Uppsala University

Start Date

11/23/2017

Completion Date

12/1/2026

Summary

Heart failure with preserved ejection fraction (HFPEF) is common and deadly but without therapy. Inconclusive studies such as TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) suggest spironolactone may be effective in HFPEF, but it is generic and will not be studied by industry. SPIRRIT is a unique Registry-Randomized Clinical Trial (RRCT) that will test the hypothesis that spironolactone plus standard of care compared to standard of care alone reduces the composite of CV mortality and HF hospitalization as follows: Population: HFPEF patients in the Swedish Heart Failure Registry and HFPEF patients in US. HFPEF defined as symptoms/signs of HF, elevated NTproBNP (B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide) and EF\>=40%. Intervention and control: Randomized 1:1 to intervention: spironolactone + usual care vs. control: usual care alone. Outcome: Primary outcome cardiovascular death or time to HF hospitalization. Secondary outcomes include hospitalization for various causes, adverse events and treatment adherence. In Sweden outcomes are obtained automatically by linking with the Population, Patient and Drug Dispensed Registries. In the US, outcomes will be reported by sites and supplemented by data from a call center. The trial is event-driven with enrollment 7 years and study duration 9 years. For the primary outcome (CV Death or first HF hospitalization) with an event target of 721 events the sample size requires 1985 patients conservatively rounded to approximately 2000 patients.

Eligibility Criteria

Age Range: 50 years to 99 years

Inclusion Criteria: * Written informed consent * Age ≥50 years * Stable heart failure defined by symptoms and signs of heart failure as judged by local Investigator * Left ventricular ejection fraction (LVEF) ≥40% recorded in last 12 months (stratified to max 2/3rd in either 40-49% or ≥50% group) * Elevated natriuretic peptide levels, as defined by any of the following: 1. most recent NT-proBNP \>300 ng/L (or BNP\>100 pg/mL) in sinus rhythm at time of blood sampling; adjustments may be made for BMI according to table 3. 2. most recent NT-proBNP \>750 ng/L (or BNP \>250 pg/mL) in atrial fibrillation at time of blood sampling; adjustments may be made for BMI according to table 3. 3. NT-proBNP \>1200 ng/L (or BNP \>400 pg/mL) within the last 12 months even if most recent value is lower. * Regular use of loop diuretics, defined as daily or most days of the week * NYHA Class II-IV Exclusion Criteria: Previously enrolled in this study * Known Ejection Fraction \< 40% ever * Current absolute indication or contraindication for MRA (mineral receptor antagonist) in judgement of Investigator * Known chronic liver disease * Probable alternative explanations for symptoms: * Known primary cardiomyopathy (hypertrophic, constrictive, restrictive, infiltrative, congenital) * Primary hemodynamically significant valve disease * Right-sided HF not due to left-sided HF * Significant chronic pulmonary disease defined by Investigator or by requirement for home O2 * Symptomatic anemia, defined as Hemoglobin \< 10 g/dL (100 g/L ) * Heart transplant or LVAD (left ventricular assist device) recipient * Presence of cardiac resynchronization therapy (CRT) device * Systolic blood pressure \<90 or \>160 mmHg * K (potassium) \>5.0 mmol/L * eGFR (estimated glomerular filtration rate) by MDRD (Modification of Diet in Renal Disease) \< 30 ml/min/1.73m2 or creatinine \> 2.5 mg/dL (221 µmol/L ) * Current lithium use * Current dialysis * Actual or potential for pregnancy * Participation in another interventional clinical trial where a mineralocorticoid receptor antagonist is studied * Any condition that in the opinion of the Investigator may interfere with adherence to trial protocol

Interventions

DRUG

Spironolactone

OTHER

Standard care

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Conditions

Heart Failure With Preserved Ejection Fraction

Locations

Advanced Cardiovascular LLC

Alexander City, Alabama 35010

United States

University of Alabama at Birmingham

Birmingham, Alabama 35294

United States

Banner - University Medical Group

Tucson, Arizona 85724

United States

MedStar Cardiovascular Research Network

Washington D.C., District of Columbia 20010

United States

Howard University Hospital

Washington D.C., District of Columbia 20060

United States

Holy Cross Hospital

Fort Lauderdale, Florida 33308

United States

Piedmont Atlanta Hospital

Atlanta, Georgia 30309

United States

Wellstar Health System, Inc.

Marietta, Georgia 30060

United States

Queens Medical Center

Honolulu, Hawaii 96813

United States

Fox Valley Clinical Research Center, LLC

Aurora, Illinois 60506-1400

United States

University of Illinois at Chicago

Chicago, Illinois 60612

United States

Alexian Brothers Medical Center

Elk Grove Village, Illinois 60007

United States

Methodist Medical Center of Illinois

Peoria, Illinois 61636

United States

St. Vincent Medical Group

Indianapolis, Indiana 46260

United States

Ochsner Medical Center

New Orleans, Louisiana 85724

United States

Shady Grove Adventist Hospital

Rockville, Maryland 20850

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Pentucket Medical Associates

Haverhill, Massachusetts 01830

United States

Charles River Medical Associates

Natick, Massachusetts 01760

United States

Newton-Wellesley Hospital

Newton, Massachusetts 02462

United States

University of Michigan Medical Center

Ann Arbor, Michigan 48109

United States

Ascension Genesys Hospital

Grand Blanc, Michigan 48439

United States

The Heart House Haddon Heights

Haddon Heights, New Jersey 08035

United States

Rutgers University - Robert Wood Johnson Medical School

New Brunswick, New Jersey 08901

United States

University of New Mexico Health Science Center

Albuquerque, New Mexico 87131

United States

University at Buffalo

Buffalo, New York 14203

United States

Northwell Health - Manhasset

Manhasset, New York 11030

United States

Mount Sinai Medical Cente

New York, New York 10029

United States

Mid Carolina Cardiology Research

Charlotte, North Carolina 28204

United States

Duke University

Durham, North Carolina 27710-4000

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45267-0542

United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania 17033

United States

Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15213

United States

Stern Cardiovascular Center

Germantown, Tennessee 38138

United States

Baylor University Medical Center

Dallas, Texas 75246

United States

University of Miami Hospital

Miami, Texas 33136

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

Angereds närsjukhus

Angered,

Sweden

Hälsostaden Ängelholms sjukhus

Ängelholm,

Sweden

Falu lasarett

Falun,

Sweden

Närsjukvården i Finspång

Finspång,

Sweden

Vårdcentralen Centrum i Flen

Flen,

Sweden

Sahgrenska University Hospital Östra

Gothenburg,

Sweden

Sahlgrenska Universitetssjukhuset

Gothenburg,

Sweden

Hemse Vårdcentral

Hemse,

Sweden

Karolinska University Hospital

Huddinge,

Sweden

Länssjukhuset Ryhov

Jönköping, 55185

Sweden

Blekingesjukhuset

Karlskrona, 37185

Sweden

Hjärtmottagningen, Centralsjukhuset

Karlstad, 65230

Sweden

Västmanlands sjukhus Köping

Köping,

Sweden

Centralsjukhuset Kristianstad

Kristianstad,

Sweden

Lasarettet i Landskrona

Landskrona,

Sweden

Skaraborgs sjukhus i Lidköping

Lidköping,

Sweden

Linköpings Universitetssjukhus

Linköping, 58185

Sweden

VO Akut- och internmedicin, Skånes Universitetssjukhus

Lund, 22185

Sweden

Capio Citykliniken

Lund,

Sweden

FO Kranskärl/Svikt, Skånes Universitetssjukhus

Lund,

Sweden

Hjärtavdelningen, Skånes Universitetssjukhus

Malmö, 20502

Sweden

Kliniska forskningsenheten Skånes Universitetssjukhus

Malmö,

Sweden

Mariefreds Vårdcentral

Mariefred,

Sweden

Sahlgrenska University Hospital Mölndal

Mölndal,

Sweden

Kardiologikliniken, Vrinnevisjukhuset

Norrköping, 60182

Sweden

Oskarshamns sjukhus

Oskarshamn,

Sweden

Örebro University Hospital

Örebro,

Sweden

Skellefteå lasarett

Skellefteå,

Sweden

Karolinska University Hospital

Solna,

Sweden

Södertälje sjukhus

Södertälje,

Sweden

VO Kardiologi, Södersjukhuset AB

Stockholm, 11883

Sweden

Capio S:t Görans sjukhus AB

Stockholm,

Sweden

Danderyds sjukhus AB

Stockholm,

Sweden

Länssjukhuset Sundsvall-Härnösand

Sundsvall,

Sweden

Sundsvalls Vårdcentral

Sundsvall,

Sweden

Uppsala University Hospital, Cardiology dept

Uppsala,

Sweden

Uppsala University Hospital, Internal Medicine dept

Uppsala,

Sweden

Medicinkliniken, Hallands sjukhus

Varberg, 43281

Sweden

Västmanlands sjukhus Västerås

Västerås,

Sweden

Västerviks sjukhus

Västervik,

Sweden