Pilot Study on Withdrawal of Spironolactone Among Heart Failure With Improved Ejection Fraction

Withdrawal of Spironolactone Treatment for Heart Failure With Improved Left Ventricular Ejection Fractraction: an Open-label Randomized Controlled Pilot Study (With-HF Trial)

The study is a randomized controlled pilot trial to evaluate whether withdrawal of spironolactone is safe and associated with re-deterioration of left ventricular function in patients with heart failure with improved ejection fraction. The aim of current trial is to test the hypothesis that withdrawal of spironolactone would not be associated with relapse of significant clinical deterioration of left ventricular systolic function.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Withdrawal of Spironolactone; Drug: Continuation of spironolactone

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of, 138-736
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and capable of providing informed consent and agrees to follow the study protocol and schedule of clinical follow-up
• Age between 19 and 80 years old
• Prior diagnosis of heart failure with reduced left ventricular ejection fraction (LV EF ≤ 35%) and on medical therapy including spironolactone combined with angiotensin-converting enzyme or angiotensin receptor blocker or antiotensin receptior neprilysin blocker, beta-blocker.
• LV EF ≥ 50% documented with echocardiography performed within a month
• Documented result of BNP or NT-proBNP level within a month

Exclusion Criteria:

• Dyspnea ≥ New York Heart Association (NYHA) functional class III
• Patients who need to discontinue spironolactone owing to prior adverse event
• Primary valvular heart disease with at least moderate degree
• Estimated glomerular filtration rate less than 30 mL/min per 1.73 m2
• Uncontrolled hypertension defined as blood pressure more than 140/90 mmHg
• Presence of other clinical reason to continue spironolactone such as myocardial infarction, primary aldosteronism, and liver cirrhosis
• Hyperkalemia defined as serum potassium level less than 3.5 mmol per liter
• Pregnant and/or lactating women
• Life expectancy less than a year
• Patients who are not suitable to enrollment by investigator's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Withdrawal group; Spironolactone will be discontinued in patients who were receiving optimal medical therapy including angiotensin-converting enzyme or angiotensin receptor blocker or angiotensin receptor neprilysin, beta-blocker, and spironolactone.	Drug: Withdrawal of Spironolactone; Other recommended medications for heart failure than spironolactone will be continued for withdrawal group.
Active Comparator: Continuation group; Spironolactone will be continued during the study period with other medical therapy in combination.	Drug: Continuation of spironolactone; Specific dose of spironolactone for continuation group is on each physician's discretion with acceptable range of 12.5 mg - 50 mg once or twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of left ventricular ejection fraction	Proportion of patients with change of left ventricular ejection fraction declining more than 10%	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical change of left ventricular ejection fraction	Comparison as continuous variable	6 month
Change of serum level on B-type natriuretic peptide or N-terminal pro-brain natriuretic peptide	Each serum level transformed with a log value and comparing with baseline level	6 months
Change of serum level of biomarkers (e.g. soluble ST-2, galectin-3)	Serum biomarkers such as soluble ST-2, galectin-3 are checked and compared with baseline value for prediction of decreased left ventricular ejection fraction	6 months
Rates of death, re-hospitalization or visit on emergency department for heart failure	Adverse clinical events	6 months
results of each outcomes during extended follow-up period	change of echocardiographic parameters, clinical events, natriuretic peptide	2 years

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: AMC_2020_0613

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No