NCT04367051

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at P25-P50 for not_applicable heart-failure

Timeline
Completed

Started Aug 2020

Geographic Reach
1 country

1 active site

Status
completed

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

April 27, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 29, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

August 13, 2020

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 10, 2021

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2022

Completed
Last Updated

October 5, 2023

Status Verified

October 1, 2023

Enrollment Period

1.3 years

First QC Date

April 27, 2020

Last Update Submit

October 4, 2023

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

  • Change of left ventricular ejection fraction

    Proportion of patients with change of left ventricular ejection fraction declining more than 10%

    6 month

Secondary Outcomes (5)

  • Numerical change of left ventricular ejection fraction

    6 month

  • Change of serum level on B-type natriuretic peptide or N-terminal pro-brain natriuretic peptide

    6 months

  • Change of serum level of biomarkers (e.g. soluble ST-2, galectin-3)

    6 months

  • Rates of death, re-hospitalization or visit on emergency department for heart failure

    6 months

  • results of each outcomes during extended follow-up period

    2 years

Study Arms (2)

Withdrawal group

EXPERIMENTAL

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

Continuation group

ACTIVE COMPARATOR

Spironolactone will be continued during the study period with other medical therapy in combination.

Drug: Continuation of spironolactone

Interventions

Withdrawal of SpironolactoneDRUG

Other recommended medications for heart failure than spironolactone will be continued for withdrawal group.

Withdrawal group
Continuation of spironolactoneDRUG

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.

Continuation group

Eligibility Criteria

Age19 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Asan Medical Center

Seoul, Songpa-gu, 138-736, South Korea

Location

Related Publications (1)

  • Hyun J, Lee SA, Lee SE, Hong JA, Kim MS, Kim JJ. Withdrawal of Spironolactone for Heart Failure With Improved Ejection Fraction: An Open-Label, Pilot, Randomized Controlled Trial (With-HF Trial). Korean Circ J. 2025 Dec;55(12):1077-1089. doi: 10.4070/kcj.2025.0052. Epub 2025 Jul 8.

    PMID: 40736394DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
professor of medicine

Study Record Dates

First Submitted

April 27, 2020

First Posted

April 29, 2020

Study Start

August 13, 2020

Primary Completion

December 10, 2021

Study Completion

June 30, 2022

Last Updated

October 5, 2023

Record last verified: 2023-10

Locations

KR(1)