Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction
SPIRRIT
3 other identifiers
interventional
2,000
2 countries
78
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2017
Longer than P75 for phase_3
78 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 9, 2016
CompletedFirst Posted
Study publicly available on registry
September 15, 2016
CompletedStudy Start
First participant enrolled
November 23, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
October 22, 2024
October 1, 2024
9 years
September 9, 2016
October 21, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (8)
Time to CV Death or first HF hospitalization
Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Time to CV Death
Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Incidence rate for total HF hospitalizations
Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Time to HF hospitalizations
Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)
Time to all-cause mortality
Collected at data base lock, five (5) years after study start
- +3 more secondary outcomes
Study Arms (2)
Spironolactone treatment
ACTIVE COMPARATORSpironolactone will be prescribed by the Investigator and filled by patient at conventional pharmacies as 25 mg tablets. The treatment will be on top of standard care. Initial dose is 25 mg/day, which will be increased to target dose 50 mg/day if tolerated. Eplerenone can be prescribed if spironolactone is not tolerated.
Standard care alone
PLACEBO COMPARATORPatients in the control arm will get the standard care alone
Interventions
Treatment with Spironolactone tablets on top of standard care
Eligibility Criteria
You may qualify if:
- 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:
- 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.
- 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.
- 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
You may not qualify if:
- 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 )
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Uppsala Universitylead
- Karolinska Universitycollaborator
- Duke Clinical Research Institutecollaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (78)
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
Malmo, 20502, Sweden
Kliniska forskningsenheten Skånes Universitetssjukhus
Malmo, 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
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lars H Lund, MD, PhD
Karolinska Institutet
- PRINCIPAL INVESTIGATOR
Bertram Pitt
University of Michigan
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 9, 2016
First Posted
September 15, 2016
Study Start
November 23, 2017
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
October 22, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share