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

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.

Conditions

• Heart Failure With Preserved Ejection Fraction

Interventions

DRUG

Spironolactone

Treatment with Spironolactone tablets on top of standard care

OTHER

Standard care

Standard care does not involve Spironolactone

Sponsors & Collaborators

• Karolinska University

  collaborator OTHER

• Duke Clinical Research Institute

  collaborator OTHER

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Uppsala University

  lead OTHER

Principal Investigators

• Lars H Lund, MD, PhD · Karolinska Institutet

• Bertram Pitt · University of Michigan

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

50 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-11-23

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

Countries

• United States
• Sweden

Study Locations