IMPRESS-AF: Improved exercise tolerance in heart failure with preserved ejection fraction by spironolactone on myocardial fibrosis in atrial fibrillation

• Register: ISRCTN
• Last refreshed on: 5 January 2021
• Main ID: ISRCTN10259346
• Date of registration: 15/01/2015
• Prospective Registration: No
• Primary sponsor: University of Birmingham
• Public title: IMPRESS-AF: Improved exercise tolerance in heart failure with preserved ejection fraction by spironolactone on myocardial fibrosis in atrial fibrillation
• Scientific title: IMPRESS-AF: IMproved exercise tolerance in heart failure with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation - an open randomised double-blind parallel-group trial
• Date of first enrolment: 01/01/2015
• Target sample size: 250
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN10259346
• Study type: Interventional
• Study design: Two-year open randomised double-blind parallel-group single-site (Treatment)
• Phase: Not Specified

Countries of recruitment

United Kingdom

Contacts

• Name: Eduard Shantsila

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 50 years old or over
2. Permanent AF as defined by the European Society of Cardiology (ESC) criteria
3. Normal BNP levels (<100 pg/mL)
4. Ability to understand and complete questionnaires (with or without use of a
translator/translated materials)

Exclusion criteria:
1. Severe systemic illness with life expectancy of less than 2 years from screening
2. Left ventricular ejection fraction (LVEF) <50% (echocardiography)
3. Severe chronic obstructive pulmonary disease (COPD) (e.g., requiring home oxygen or chronic oral steroid therapy)
4. Severe mitral/aortal valve stenosis/regurgitation
5. Significant renal dysfunction (serum creatinine 220 µmol/L or above), anuria, active renal insufficiency, rapidly progressing or sever impairment of renal function, confirmed or suspected renal insufficiency in diabetic patients/ diabetic nephropathy
6. Increase in potassium level to > 5mmol/L)
7. Recent coronary artery bypass graft surgery (within 3 months)
8. Use of aldosterone antagonist within 14 days before randomisation
9. Use of or potassium sparing diuretic within 14 days before randomisation
10. Systolic blood pressure >160 mm Hg
11. Addison’s disease
12. Hypersensitivity to spironolactone or any of the ingredients in the product
13. Any participant characteristic that may interfere with adherence to the trial protocol


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Treatment of symptomatic patients with atrial fibrillation with preserved ejection fraction
Circulatory System
Atrial fibrillation and flutter

Intervention(s)

The study patients will be randomised to receive spironolactone or placebo (i.e., two-arm study). Study patients and researchers will be blinded to treatment allocation. Placebo and spironolactone will be identical in appearance and packaging and manufactured as 25-mg tablets in accordance with national and international standards. Patients will be instructed to take the study drug at one capsule once daily after randomisation. There is no up-titration planned.

In the case of an increase in potassium level to 5.1-5.5 mmol/L or in the presence of other non-life-threatening side effects (such as gynaecomastia) the trial drug will be down-titrated to 25 mg each second day. In such cases, the investigators are advised to re-up-titrate the trial medication if the reason for down-titration has resolved. Routine laboratory surveillance of serum potassium, sodium, full blood count with hematocrit, and renal function will be done by protocol at each visit and within 1 week of any dose adjustment.

Drug toxicity will be defined as an increase in potassium level to >5.5 mmol/L. In the case of toxicity or suspected toxicity, the trial medication will be stopped for the duration of the trial, but the patient will be requested to attend the remaining follow-up visits.

The trial treatment will be administered during 2 years with no further follow-up planned.

The protocol calls for current optimised management of AF and any background cardiac pathology as per current guidelines.

Primary Outcome(s)

Exercise tolerance (peak VO2 on cardio-pulmonary exercise testing); Timepoint(s): 2 years of treatment

Secondary Outcome(s)

1. Diastolic function measured by echocardiography; Timepoint(s): After 2 years of treatment
2. Exercise tolerance measured by 6-minute walking test; Timepoint(s): 2 years of treatment
3. Health-related quality of life (assessed using the validated questionnaires); Timepoint(s): After 2 years of treatment
4. Rates of all-cause hospitalisations; Timepoint(s): After 2 years of treatment
5. Sinus rhythm; Timepoint(s): After 2 years of treatment

Secondary ID(s)

NCT02673463

18080

2014-003702-33

Source(s) of Monetary Support

National Institute for Health Research

Ethics review

Status:
Approval date:
Contact:

Coventry and Warwickshire Research Ethics Committee, 07/01/2015, ref: 14/WM/1211

Results

• Results available: Yes
• Date Completed: 30/09/2017