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

Study Overview
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Brief Summary
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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.

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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Withdrawal of Spironolactone
* Drug: Continuation of spironolactone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Withdrawal group<br>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<br>* Other recommended medications for heart failure than spironolactone will be continued for withdrawal group.<br>|
| Active Comparator: Continuation group<br>Spironolactone will be continued during the study period with other medical therapy in combination. | Drug: Continuation of spironolactone<br>* 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.<br>|

What is the study measuring?
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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 |