Clinical trial NCT02673463: Spironolactone in Atrial Fibrillation
Official title: Improved Exercise Tolerance in Participants With PReserved Ejection Fraction by Spironolactone on Myocardial Fibrosis in Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: University of Birmingham
Sponsor class: OTHER
First posted: 2016-02-04
Enrollment: 250
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Exercise tolerance (cardiopulmonary exercise testing)
timeFrame: 2 years of treatment
Secondary outcomes:
measure: Quality of life (MLWHF)
timeFrame: 2 years of treatment
measure: Quality of life (EQ-5D)
timeFrame: 2 years of treatment
measure: Left ventricular diastolic function
timeFrame: 2 years of treatment
measure: Exercise tolerance (6-minute walk test)
timeFrame: 2 years of treatment
measure: Rates of all-cause hospitalisations
timeFrame: 2 years of treatment
measure: Spontaneous return to sinus rhythm on electrocardiogram
timeFrame: 2 years of treatment
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University of Birmingham Institute of Cardiovascular Sciences
state: West Midlands
Study officials:
affiliation: University of Birmingham
name: Gregory YH Lip, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Birmingham
name: Eduard Shantsila, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Birmingham
name: Paulus Kirchhof, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shantsila E, Shahid F, Sun Y, Deeks J, Calvert M, Fisher JP, Kirchhof P, Gill PS, Lip GYH. Spironolactone in Atrial Fibrillation With Preserved Cardiac Fraction: The IMPRESS-AF Trial. J Am Heart Assoc. 2020 Sep 15;9(18):e016239. doi: 10.1161/JAHA.119.016239. Epub 2020 Sep 10.
citation: Shantsila E, Haynes R, Calvert M, Fisher J, Kirchhof P, Gill PS, Lip GY. IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial. BMJ Open. 2016 Oct 5;6(10):e012241. doi: 10.1136/bmjopen-2016-012241.