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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— SPIRRIT  

Official title:

Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction, SPIRRIT-HFPEF

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02901184
• Other study ID #: U-2015-030
• Secondary ID: U01HL134679-01U0
• Status: Recruiting
• Phase: Phase 3
• Start date: November 23, 2017
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Uppsala University
• Contact: Anna Gustavsson (SWE)
• Phone: +46186110181
• Email: anna.gustavsson[@]ucr.uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• Spironolactone
Treatment with Spironolactone tablets on top of standard care

Other:
• Standard care
Standard care does not involve Spironolactone

Locations

Country	Name	City	State
Sweden	Hälsostaden Ängelholms sjukhus	Ängelholm
Sweden	Angereds närsjukhus	Angered
Sweden	Falu lasarett	Falun
Sweden	Närsjukvården i Finspång	Finspång
Sweden	Vårdcentralen Centrum i Flen	Flen
Sweden	Sahgrenska University Hospital Östra	Göteborg
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Hemse Vårdcentral	Hemse
Sweden	Karolinska University Hospital	Huddinge
Sweden	Länssjukhuset Ryhov	Jönköping
Sweden	Blekingesjukhuset	Karlskrona
Sweden	Hjärtmottagningen, Centralsjukhuset	Karlstad
Sweden	Västmanlands sjukhus Köping	Köping
Sweden	Centralsjukhuset Kristianstad	Kristianstad
Sweden	Lasarettet i Landskrona	Landskrona
Sweden	Skaraborgs sjukhus i Lidköping	Lidköping
Sweden	Linköpings Universitetssjukhus	Linköping
Sweden	Capio Citykliniken	Lund
Sweden	FO Kranskärl/Svikt, Skånes Universitetssjukhus	Lund
Sweden	VO Akut- och internmedicin, Skånes Universitetssjukhus	Lund
Sweden	Hjärtavdelningen, Skånes Universitetssjukhus	Malmö
Sweden	Kliniska forskningsenheten Skånes Universitetssjukhus	Malmö
Sweden	Mariefreds Vårdcentral	Mariefred
Sweden	Sahlgrenska University Hospital Mölndal	Mölndal
Sweden	Kardiologikliniken, Vrinnevisjukhuset	Norrköping
Sweden	Örebro University Hospital	Örebro
Sweden	Oskarshamns sjukhus	Oskarshamn
Sweden	Skellefteå lasarett	Skellefteå
Sweden	Södertälje sjukhus	Södertälje
Sweden	Karolinska University Hospital	Solna
Sweden	Capio S:t Görans sjukhus AB	Stockholm
Sweden	Danderyds sjukhus AB	Stockholm
Sweden	VO Kardiologi, Södersjukhuset 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
Sweden	Västmanlands sjukhus Västerås	Västerås
Sweden	Västerviks sjukhus	Västervik
United States	University of New Mexico Health Science Center	Albuquerque	New Mexico
United States	Advanced Cardiovascular LLC	Alexander City	Alabama
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Fox Valley Clinical Research Center, LLC	Aurora	Illinois
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University at Buffalo	Buffalo	New York
United States	Mid Carolina Cardiology Research	Charlotte	North Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Stern Cardiovascular Center	Germantown	Tennessee
United States	Ascension Genesys Hospital	Grand Blanc	Michigan
United States	The Heart House Haddon Heights	Haddon Heights	New Jersey
United States	Pentucket Medical Associates	Haverhill	Massachusetts
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Queens Medical Center	Honolulu	Hawaii
United States	St. Vincent Medical Group	Indianapolis	Indiana
United States	Northwell Health - Manhasset	Manhasset	New York
United States	Wellstar Health System, Inc.	Marietta	Georgia
United States	University of Miami Hospital	Miami	Texas
United States	Charles River Medical Associates	Natick	Massachusetts
United States	Rutgers University - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Mount Sinai Medical Cente	New York	New York
United States	Newton-Wellesley Hospital	Newton	Massachusetts
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Shady Grove Adventist Hospital	Rockville	Maryland
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Banner - University Medical Group	Tucson	Arizona
United States	Howard University Hospital	Washington	District of Columbia
United States	MedStar Cardiovascular Research Network	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
Uppsala University	Duke Clinical Research Institute, Karolinska University, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate for total heart failure (HF) hospitalizations or cardiovascular (CV) death	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	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Time to CV Death or first HF hospitalization	Sweden: Information on Death from the Swedish Causes of death registry US: Collected in eCRF or via call center interview	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Time to CV Death	Sweden: Information on Death from the Swedish Causes of death registry US: Collected in eCRF or via call center interview	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Incidence rate for total HF hospitalizations	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	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Time to HF hospitalizations	Sweden: Information on information on hospitalization collected from Swedish Patient Registry.; US: Collected in eCRF or via call center interview	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Time to all-cause mortality	Sweden: Information on Death from the Swedish Causes of death registry. US: Collected in eCRF or via call center interview	Collected at data base lock, five (5) years after study start
Secondary	Incidence rate for all-cause hospitalizations	Sweden: Information on information on hospitalization collected from Swedish Patient Registry.; US: Collected in eCRF or via call center interview	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Time to all-cause hospitalizations	Sweden: Information on information on hospitalization collected from Swedish Patient Registry.; US: Collected in eCRF or via call center interview	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Secondary	Incidence rate for all-cause hospitalizations or all-cause mortality	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	Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)