Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF)

Condition(s) targeted: Permanent Atrial Fibrillation

Intervention: Bisoprolol (Drug); Digoxin (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: University of Birmingham

Official(s) and/or principal investigator(s):
Dipak Kotecha, MBChB PhD MRCP, Principal Investigator, Affiliation: University of Birmingham

Overall contact:
Dipak Kotecha, MBChB PhD MRCP, Phone: +447974115676, Email: d.kotecha@bham.ac.uk

Atrial fibrillation is a common heart rhythm disturbance, causing important discomfort for patients, a high risk of stroke, frequent hospital admissions and a two-fold increase in death. The number of patients with this condition are expected to double in the next 20 years. Medications to control heart-rate are used in the majority of patients, although the choice of agent is often guided by local preference rather than evidence from controlled trials. Despite the fact that patients with atrial fibrillation have high rates of other cardiac conditions such as heart failure, clinicians have insufficient evidence to personalise the use of different therapies. This feasibility study will allow us to develop a range of methods that can characterise patients according to the pumping and relaxing function of the heart, the burden of symptoms and to identify new blood markers. In this way, the investigators hope to improve clinical practice guidelines, allowing doctors to prescribe appropriate treatments for the right patients. The research will be focused around a randomised trial of two medication strategies, providing much-needed data on the comparison of digoxin and beta-blockers (two commonly-used drugs in patients with atrial fibrillation). It will also allow us to identify the best way to record patient-reported quality of life and develop robust techniques to determine heart function using non-invasive imaging, facilitating the conduct of a large-scale clinical trial. The key objectives of the research programme are to define the optimal medications for patients with atrial fibrillation and identify the most valid, reproducible and cost-effective methods to examine patients. The ultimate aim of the project is to improve clinical outcomes in atrial fibrillation, benefiting patients, the National Health Service and the global community.

Official title: Evaluating Different Rate Control Therapies in Permanent Atrial Fibrillation: A Prospective, Randomised, Open-label, Blinded Endpoint Feasibility Pilot Comparing Digoxin and Beta-blockers as Initial Rate Control Therapy

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Composite of feasibility/pilot objectives to plan a future definitive event-driven outcome trial

Co-primary efficacy outcome: Patient reported quality of life

Co-primary efficacy outcome: Echocardiographic left-ventricular function

Secondary outcome:

Hospitalisation

B-type natriuretic peptide (BNP)

Composite functional status measures

Drug discontinuation rate due to adverse reactions

Therapy-induced requirement for additional investigation and treatment

Time to all-cause death

Composite of major adverse cardiovascular events

Patient reported outcomes over 12 months

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Adult patients aged 18 years or older, able to provide informed written consent 2. Permanent AF, characterised (at time of randomisation) as a physician decision for rate-control with no plans for cardioversion, anti-arrhythmic medication, or ablation therapy 3. All patients must complete baseline QoL questionnaires 4. All patients should be prescribed an oral anticoagulant if the CHA2DS2-VASc score is ≥1 (unless specific contraindication noted) Exclusion Criteria: 1. Patients with severe systolic heart failure (LVEF ≤25%) 2. Myocardial infarction in the last 6 months 3. Any other specific indication for beta-blocker therapy 4. Known intolerance of beta-blockers or digoxin 5. A history of severe bronchospasm (e. g. due to asthma) that would preclude use of beta-blockers 6. Baseline heart rate <60 bpm 7. History of second or third-degree heart block 8. Supraventricular arrhythmias associated with accessory conducting pathways (e. g. Wolff-Parkinson-White syndrome) or a history of ventricular tachycardia or fibrillation 9. Planned pacemaker implantation, pacemaker-dependent rhythm or history of atrioventricular node ablation 10. Baseline systolic blood pressure <90mmHg 11. Hypokalaemia (serum potassium <3. 5mmol/L) 12. Estimated glomerular filtration rate (GFR) <30mL/min or receiving renal replacement therapy 13. Initiation of cardiac resynchronization therapy (with/without defibrillator) within 6 months prior to randomisation 14. Intravenous infusions for heart failure (inotropes, vasodilators or diuretics) within 7 days prior to randomisation 15. A current diagnosis of hypertrophic cardiomyopathy, myocarditis or constrictive pericarditis 16. Received or on waiting list for heart transplantation 17. Major surgery, including thoracic or cardiac surgery, within 3 months of randomisation 18. Severe, concomitant non-cardiovascular disease (including malignancy) that is expected to reduce life expectancy to less than 3 years 19. Pregnancy or breast feeding (women of reproductive potential advised to use highly effective contraception methods)

Dipak Kotecha, MBChB PhD MRCP, Phone: +447974115676, Email: d.kotecha@bham.ac.uk

City Hospital, Birmingham, West Midlands, United Kingdom; Not yet recruiting

Queen Elizabeth Hospital, Birmingham, West Midlands, United Kingdom; Not yet recruiting

Related publications:

Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, Lip GY, Coats AJ, Andersson B, Kirchhof P, von Lueder TG, Wedel H, Rosano G, Shibata MC, Rigby A, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014 Dec 20;384(9961):2235-43. doi: 10.1016/S0140-6736(14)61373-8. Epub 2014 Sep 2.

Starting date: December 2015
Last updated: March 12, 2015