Spironolactone in Atrial Fibrillation

Study Overview
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Brief Summary
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This study aims to assess whether treatment with a drug called spironolactone, which is an aldosterone inhibitor, can improve ability to cope with exertion, quality of life and ability of the heart to relax better in symptomatic patients with atrial fibrillation with preserved pumping capacity.

Detailed Description
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IMPRESS-AF study is a double-blinded randomised placebo-controlled trial of 2-year treatment with an aldosterone antagonist, spironolactone (25mg once daily) vs placebo in 250 patients with symptomatic chronic atrial fibrillation and preserved left ventricular contractility (both added to the current optimised care). The trial will establish impact of spironolactone on the primary outcome of exercise tolerance (peak oxygen consumption on cardiopulmonary exercise testing) and secondary outcomes: (i) health-related quality of life (assessed using the validated Minnesota Living with Heart Failure and EuroQol EQ-5D questionnaires self-completed by patients), and (ii) left ventricular diastolic function (E/e' ratio on echocardiography) - all assessed at baseline and at 2 years; (iii) rates of all-cause hospitalisations during 2-year follow-up.

Official Title
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Improved Exercise Tolerance in Participants With PReserved Ejection Fraction by Spironolactone on Myocardial Fibrosis in Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Permanent AF Left ventricular ejection fraction >= 55% as established by echocardiography Able to perform cardio-pulmonary exercise testing using a cycling ergometer and complete quality of life questionnaires in English or in their native language. Exclusion Criteria: Severe systemic illness (life expectancy <2 years) Severe chronic obstructive pulmonary disease (e.g., requiring home oxygen or chronic oral steroid therapy) Severe mitral/aortal valve stenosis/regurgitation Significant renal dysfunction (serum creatinine 220 µmol/L or above), anuria, active renal insufficiency, rapidly progressing or severe impairment of renal function, confirmed or suspected renal insufficiency in diabetic patients/ diabetic nephropathy Increase in potassium level to >5mmol/L Recent coronary artery bypass graft surgery (within 3 months) Use of aldosterone antagonist within 14 days before randomisation Use of or potassium sparing diuretic within 14 days before randomisation Systolic blood pressure >160 mm Hg Addison's disease Hypersensitivity to spironolactone or any of the ingredients in the product Any participant characteristic that may interfere with adherence to the trial protocol

Ages Eligible for Study
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Minimum Age: 50 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spironolactone<br>Spironolactone 25 mg once daily for 2 years | Drug: Spironolactone<br>* 25 mg once daily<br>* Other names: Aldactone;|
| Placebo Comparator: Placebo<br>Matched placebo once daily for 2 years | Drug: Placebo<br>* Visually identical to spironolactone, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise tolerance (cardiopulmonary exercise testing) | Improvement in exercise tolerance (assessed using peak oxygen consumption on cardiopulmonary exercise testing) | 2 years of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (MLWHF) | Improvement in quality of life assessed using MLWHF questionnaire | 2 years of treatment | 
| Quality of life (EQ-5D) | Improvement in quality of life assessed using EQ-5D questionnaire | 2 years of treatment | 
| Left ventricular diastolic function | Improvement in diastolic function assessed using echocardiography (E/e' ratio) | 2 years of treatment | 
| Exercise tolerance (6-minute walk test) | Improvement in exercise tolerance (assessed using 6-minute walk test) | 2 years of treatment | 
| Rates of all-cause hospitalisations |  | 2 years of treatment | 
| Spontaneous return to sinus rhythm on electrocardiogram |  | 2 years of treatment |