NCT04727073

Spironolactone in the Treatment of Heart Failure

Spironolactone in the Treatment of Heart Failure- a Double-blind, Randomized, Placebo-controlled, Parallel Group Interventional Phase III Study to Determine Efficacy and Safety of Spironolactone on the Composite Endpoint of Recurrent Heart Failure Hospitalizations and Cardiovascular Death in Patients with Heart Failure with Mid-range or Preserved Ejection Fraction

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 743 (actual)
• Sponsor: Charite University, Berlin, Germany · Academic / Other
• Sex: All
• Age: 50 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether the treatment of patients with HFmrEF and HFpEF at high risk of cardiovascular events with the mineralocorticoid receptor antagonist (MRA) spironolactone reduces a composite of recurrent heart failure hospitalizations and cardiovascular mortality.

Detailed description

The primary objective of the SPIRIT-HF study is to compare Spironolactone to Placebo in reducing the rate of the composite endpoint of recurrent heart failure hospitalizations and cardiovascular (CV) death in symptomatic HF patients (NYHA II-IV) with mid-range (LVEF 40- 49 %) or preserved (LVEF ≥ 50 %) ejection fraction. The efficacy and safety of mineralocorticoid receptor antagonist (MRA) in reducing the risk of death and hospitalizations has been proven with two separate substances (Spironolactone; RALES 1999 and Eplerenone; EMPHASIS 2011) in symptomatic heart failure patients with reduced left- ventricular ejection fraction (HFrEF). In 2013 the TOPCAT investigators tried to proof similar efficacy in patients with heart failure and preserved ejection fraction (≥ 45%). Because of regional variations in the enrollment process and difficulties regarding drug adherence the trial revealed neutral findings but the substance spironolactone was still able to show its potential benefit in the American cohort. Hence, the investigators see a strong rationale for testing a mineralocorticoid receptor blocker in patients suffering from heart failure with mid-range or preserved left ventricular ejection fraction. Intervention: Mineralocorticoid receptor blocker Spironolactone in tablet form taken daily. Starting dosage will be 25 mg OD with dosage escalation to 50 mg OD within 4 weeks if kidney function at VR was \> 30 mL/min/m2 and potassium \< 4.5 mmol/L. Spironolactone is not approved for the treatment of HFmrEF and HFpEF. Matching placebo in tablet form taken daily with dosage escalation rules in accordance with dosage of the study drug Spironolactone. Visits: Screening (VScr), Visit of Randomization (VR), V1 Safety Visit (1 week), V2 (4 weeks), V2S Safety Visit (5 week), V3 (4 months), V4 (8 months), V5 (12 months), V6 (18 months), V7 (24 months), V8 (30 months), V9 (36 months), V10 (42 months), V11/EOT (48 months); VXS (1 week after Visit X). Individual intervention duration with spironolactone or placebo will be continued until the overall expected event rate is reached or until withdrawal of informed consent. Based on previous HF trials the investigators calculate a mean follow-up duration of 3 years (range 2-4 years) depending on the individual inclusion date. Duration of follow-up will be event-rate based, with an expected overall study duration of 60 months. With an anticipated recruitment phase of 24 months; this will result in a maximum follow-up of 48 months and an average follow-up per patient of 36 months assuming a constant recruitment rate.

Conditions

• Heart Failure with Mid-range Ejection Fraction
• Heart Failure with Preserved Ejection Fraction

Interventions

Type	Name	Description
DRUG	Experimental: Spironolactone	Spironolactone (an aldosterone antagonist) in tablet form taken daily. The initial study drug dose is 25 mg/day (one tablet) and may be titrated up to 50 mg/day (two tablets) within 4 weeks if kidney function at VR was \> 30 mL/min/m2 and potassium \< 4.5 mmol/L.
DRUG	Placebo Comparator	Placebo of Spironolactone in tablet form taken daily with dosage escalation rules in accordance with dosage of the study drug Spironolactone.

Timeline

• Start date: 2018-11-01
• Primary completion: 2024-10-01
• Completion: 2024-10-01
• First posted: 2021-01-27
• Last updated: 2025-03-28

Locations

69 sites across 5 countries: Austria, France, Germany, Netherlands, Serbia