IMPRESS-AF: Improved exercise tolerance in heart failure with preserved ejection fraction by spironolactone on myocardial fibrosis in atrial fibrillation
| ISRCTN | ISRCTN10259346 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10259346 |
| EudraCT/CTIS number | 2014-003702-33 |
| ClinicalTrials.gov number | NCT02673463 |
| Secondary identifying numbers | 18080 |
- Submission date
- 14/01/2015
- Registration date
- 15/01/2015
- Last edited
- 17/12/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English Summary
Background and study aims
Atrial fibrillation is a heart rhythm problem (arrhythmia) which causes the heart to beat irregularly and often at an abnormally fast pace. In these cases, the heart is often unable to supply enough blood to the body (a condition called ‘heart failure’). In about half of all heart failure patients the heart contracts reasonably well, but it does not relax properly because it is very stiff and so does not fill with sufficient blood between heart beats. These patients have a poor quality of life and a high risk of death, just as those heart failure patients who have hearts that contract poorly. There is a clear need to find beneficial therapies for such patients. The reason why patients with atrial fibrillation tend to have stiff hearts that fill poorly and develop heart failure is not known, but high levels of aldosterone have been suggested to play an important role. Aldosterone is normally produced by the kidney, travels in the blood, and has a wide range of affects throughout the body. We think that raised aldosterone levels may explain the stiffening of the heart and its poor filling in patients with atrial fibrillation and heart failure. The effects of aldosterone can be blunted with the drug spironolactone, and with this clinical trial we want to find out if giving spironolactone to patients with atrial fibrillation improves the way their hearts relax and so increases their ability to perform exercise and improving their quality of life.
Who can participate?
Adults aged 50 or over, with permanent atrial fibrillation and normal levels of the hormone called brain natriuretic peptide.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 are treated with spironolactone for two years. Those in group 2 are treated with a placebo for two years. We then measure each participants tolerance to exercise, assess their health-related quality of life, assess the ability of the heart to relax (diastolic function measured by echocardiography) and also look at rates of hospitalisations (regardless of cause) during the trial. Participants are blinded to their group allocation.
What are the possible benefits and risks of participating?
The study treatment aims to improve exercise performance of quality of life of the participants. The study drug benefits from a very well established safety profile with possible side effects (such as increase in blood potassium) being usually mild and disappearing on stopping the drug.
Where is the study run from?
University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
January 2015 to October 2017
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Eduard Shantsila
Contact information
Scientific
University of Birmingham
Department of Cardiovascular Medicine
Medical School
Edgbaston
Birmingham
B15 2TT
United Kingdom
Study information
| Study design | Two-year open randomised double-blind parallel-group single-site |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a patient information sheet |
| 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 |
| Study acronym | IMPRESS-AF |
| Study hypothesis | It is hypothesised that in symptomatic patients with permanent AF with normal BNP levels treatment with spironolactone will improve exercise tolerance as a surrogate for cardiovascular mortality/morbidity (primary outcome), and will improve quality of life and diastolic function, as well as reduce the rate of all-cause hospital admissions, and increase rate of spontaneous cardioversion to sinus rhythm (secondary outcomes). |
| Ethics approval(s) | Coventry and Warwickshire Research Ethics Committee, 07/01/2015, ref: 14/WM/1211 |
| Condition | Treatment of symptomatic patients with atrial fibrillation with preserved ejection fraction |
| Intervention | 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. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | |
| Drug / device / biological / vaccine name(s) | Spironolactone |
| Primary outcome measure | Exercise tolerance (peak VO2 on cardio-pulmonary exercise testing); Timepoint(s): 2 years of treatment |
| Secondary outcome measures | 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 |
| Overall study start date | 01/01/2015 |
| Overall study end date | 30/09/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 250; UK Sample Size: 250 |
| Total final enrolment | 250 |
| Participant 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) |
| Participant 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 |
| Recruitment start date | 01/01/2015 |
| Recruitment end date | 31/12/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Birmingham
B15 2TT
United Kingdom
Sponsor information
Hospital/treatment centre
Department of Cardiovascular Medicine
Medical School
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/07/2020 | 17/12/2020 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/12/2020: Publication reference, total final enrolment and ClinicalTrials.gov number added.
