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

NCT02901184 · tracked via the Priya Life Science Sweden tracker

Sponsor

Uppsala University

Phase

Phase 3

Started

2017-11-23

Last updated

2024-10-22

Condition(s) studied

Heart Failure With Preserved Ejection Fraction

Investigational drug(s) / intervention(s)

Spironolactone →Standard care

Spironolactone: Treatment with Spironolactone tablets on top of standard care

Standard care: Standard care does not involve Spironolactone

Study 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

Sex

ALL

Min age

50 Years

Max age

99 Years

Healthy volunteers

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

Primary outcome measure(s)

Incidence rate for total heart failure (HF) hospitalizations or cardiovascular (CV) death — Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Sweden: Information on Death from the Swedish Causes of death registry and information on hospitalization collected from Swedish Patient Registry US: Collected in eCRF or via call center interview

Trial sites (78)

Facility	City	Region	Status
Advanced Cardiovascular LLC	Alexander City	Alabama	Terminated
University of Alabama at Birmingham	Birmingham	Alabama	Terminated
Banner - University Medical Group	Tucson	Arizona	Terminated
MedStar Cardiovascular Research Network	Washington D.C.	District of Columbia	Terminated
Howard University Hospital	Washington D.C.	District of Columbia	Terminated
Holy Cross Hospital	Fort Lauderdale	Florida	Terminated
Piedmont Atlanta Hospital	Atlanta	Georgia	Terminated
Wellstar Health System, Inc.	Marietta	Georgia	Terminated
Queens Medical Center	Honolulu	Hawaii	Terminated
Fox Valley Clinical Research Center, LLC	Aurora	Illinois	Terminated
University of Illinois at Chicago	Chicago	Illinois	Terminated
Alexian Brothers Medical Center	Elk Grove Village	Illinois	Terminated
Methodist Medical Center of Illinois	Peoria	Illinois	Terminated
St. Vincent Medical Group	Indianapolis	Indiana	Terminated
Ochsner Medical Center	New Orleans	Louisiana	Terminated
Shady Grove Adventist Hospital	Rockville	Maryland	Terminated
Brigham and Women's Hospital	Boston	Massachusetts	Terminated
Pentucket Medical Associates	Haverhill	Massachusetts	Terminated
Charles River Medical Associates	Natick	Massachusetts	Terminated
Newton-Wellesley Hospital	Newton	Massachusetts	Terminated
University of Michigan Medical Center	Ann Arbor	Michigan	Terminated
Ascension Genesys Hospital	Grand Blanc	Michigan	Terminated
The Heart House Haddon Heights	Haddon Heights	New Jersey	Terminated
Rutgers University - Robert Wood Johnson Medical School	New Brunswick	New Jersey	Terminated
University of New Mexico Health Science Center	Albuquerque	New Mexico	Terminated
University at Buffalo	Buffalo	New York	Terminated
Northwell Health - Manhasset	Manhasset	New York	Terminated
Mount Sinai Medical Cente	New York	New York	Terminated
Mid Carolina Cardiology Research	Charlotte	North Carolina	Terminated
Duke University	Durham	North Carolina	Terminated
University of Cincinnati Medical Center	Cincinnati	Ohio	Terminated
Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	Terminated
Jefferson University Hospital	Philadelphia	Pennsylvania	Terminated
University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	Terminated
Stern Cardiovascular Center	Germantown	Tennessee	Terminated
Baylor University Medical Center	Dallas	Texas	Terminated
University of Miami Hospital	Miami	Texas	Terminated
University of Texas Health Science Center at San Antonio	San Antonio	Texas	Terminated
Angereds närsjukhus	Angered	Sweden	Terminated
Hälsostaden Ängelholms sjukhus	Ängelholm	Sweden	Terminated

+ 38 more sites — see the full list on the official registry below.

On this site

📄 Aldactone (spironolactone) drug profile →

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT02901184 on ClinicalTrials.gov ↗ ← All trials in Sweden