Plain English Summary
Background and study aims
Atrial fibrillation (AF) is a common heart condition that around 1 in 4 adults are at risk of developing. It is caused by a fault in the electrical control centre in the heart which is found in the upper right chamber (right atrium), causing it to fire erratically. These uncoordinated signals cause the heart to beat irregularly and often very fast (arrhythmia). Sufferers are typically elderly and often have a number of other medical conditions, including high blood pressure and heart failure. In addition, AF is a common cause of stroke, hospital admissions and early death, and leads to reduced quality of life. An important part of AF treatment is the control of heart rate however evidence as to which medication is the best for rate-control is and whether it can improve quality of life or heart function is currently lacking. The aim of this study is to find out which, of two treatments (digoxin or bisoprolol), improves quality of life and heart function.
Who can participate?
Adults aged 60 and over who have AF and symptoms of breathlessness.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are treated with digoxin through a drip once a day for 12 months. Those in the second group are treated with bisoprolol through a drip once a day for 12 months. In both groups, the dosage will vary depending on each participant’s clinical need. At the start of the study and then after 6 and 12 months, participants in both groups complete a number of questionnaires to assess their quality of life, heart monitoring to assess their heart function and blood testing to see how well their bodies are responding to treatment.
What are the possible benefits and risks of participating?
Although there may be no direct benefit to those participating, it is hoped that this study will benefit all future patients with atrial fibrillation. Patient will benefit from being seen more regularly than normal because they are taking part in a study and will have access to the expert study team. There is a small risk that having to take part in the questionnaires, tests and visits to the hospital might be an inconvenience. There is also a small risk of bruising or discomfort during blood tests.
Where is the study run from?
The study is run from Queen Elizabeth Hospital, City Hospital and Sandwell General Hospital and takes place at General practitioners in the Birmingham area (UK)
When is the study starting and how long is it expected to run for?
March 2016 to August 2019
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Dipak Kotecha
d.kotecha@bham.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Dipak Kotecha
ORCID ID
http://orcid.org/0000-0002-2570-9812
Contact details
Institute of Cardiovascular Sciences
University of Birmingham
Medical School
Vincent Drive
Birmingham
B15 2TT
United Kingdom
+44 (0)7974 115676
rate-af@trials.bham.ac.uk
Additional identifiers
EudraCT number
2015-005043-13
ClinicalTrials.gov number
Protocol/serial number
32563
Study information
Scientific title
Evaluating different rate control therapies in permanent atrial fibrillation: a prospective, randomised, open-label, blinded endpoint study comparing digoxin and beta-blockers as initial rate control therapy. RAte control Therapy Evaluation in permanent Atrial Fibrialltion (RATE-AF)
Acronym
RATE-AF
Study hypothesis
The aim of this study is to compare two strategies of rate-control in patients with atrial fibrillation (AF), based either on initial treatment with digoxin or beta-blockers.
Ethics approval
East Midlands - Derby Research Ethics Committee, 18/07/2016, ref: 16/EM/0178
Study design
Randomised; Interventional; Design type: Treatment, Process of Care, Drug
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Specialty: Cardiovascular disease, Primary sub-specialty: Other; UKCRC code/ Disease: Cardiovascular/ Other forms of heart disease
Intervention
Participants are be randomised to one of two groups in a 1:1 ratio by a computer generated and stratified minimisation algorithm:
Group 1: Participants receive Digoxin 62.5 – 250 micrograms once daily uptitrated according to response and symptoms.
Group 2: Participants receive Bisoprolol 1.25 – 15 mg once daily uptitrated according to response and symptoms.
Patients in both groups will remain on treatment for 12 months as part of the trial.
The trial is testing the initial randomisation to either a digoxin or beta-blocker strategy. In both groups, additional therapy will likely be needed over the course of the trial.
Follow-up takes place at 6 and 12 months, and involves quality of life measurement, heart ultrasound (echocardiography), blood tests and assessment of function (questionnaires and a walking test).
Most patients will continue their treatment after the trial, according to their needs.
Intervention type
Other
Phase
Phase IV
Drug names
Primary outcome measures
Patient-reported quality of life is measured using the SF-36 physical component summary score at baseline and 6 months
Secondary outcome measures
1. Patient-reported quality of life is measured using SF-36 global and domain-specific scores, EQ-5D-5L summary index and visual analogue scale and AFEQT overall score at baseline, 6 and 12 months
2. Cardiac function is assessed by measuring echocardiographic left ventricular ejection fraction and diastolic function (E/e’ and composite of diastolic indices) at baseline and 12 months
3. Six-minute walking distance is measured at baseline, 6 and 12 months
4. European Heart Rhythm Association (EHRA) functional class information is checked at baseline, 6 and 12 months
5. B-type natriuretic peptide (BNP) levels and other biomarkers of treatment response are measured using blood testing at baseline, 6 and 12 months
6. Heart rate control is measured using 24-hour ambulatory ECG at approximately 3 months
Overall trial start date
23/03/2016
Overall trial end date
31/08/2019
Reason abandoned
Eligibility
Participant inclusion criteria
1. Adult patients aged 60 years or older
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. Symptoms of breathlessness (New York Heart Association Class II or more)
4. Able to provide written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 160; UK Sample Size: 160
Participant exclusion criteria
1. Established clinical indication for beta-blocker therapy, e.g. myocardial infarction in the last 6 months
2. Known contraindications for therapy with beta-blockers or digoxin, e.g. a history of severe bronchospasm that would preclude use of beta-blockers, or known intolerance to these medications
3. Baseline heart rate history of atrioventricular node ablation
4. Decompensated heart failure (evidenced by need for intravenous inotropes, vasodilators or diuretics) within 14 days prior to randomisation
5. A current diagnosis of obstructive hypertrophic cardiomyopathy, myocarditis or constrictive pericarditis
6. Received or on waiting list for heart transplantation
7. Receiving renal replacement therapy
8. Major surgery, including thoracic or cardiac surgery, within 3 months of randomisation
9. Severe, concomitant non-cardiovascular disease (including malignancy) that is expected to reduce life expectancy
Recruitment start date
05/12/2016
Recruitment end date
31/03/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
University Hospital Birmingham NHS Trust
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Trial participating centre
City Hospital
Sandwell and West Birmingham Hospitals NHS Trust
Dudley Road
Birmingham
B18 7QH
United Kingdom
Trial participating centre
Sandwell General Hospital
Sandwell and West Birmingham Hospitals
Lyndon
West Bromwich
B71 4HJ
United Kingdom
Sponsor information
Organisation
University of Birmingham
Sponsor details
Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 414 8165
researchgovernance@contacts.bham.ac.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The Chief Investigator will coordinate dissemination of data from this trial (likely publication mid-2019). All publications and presentations, including abstracts, relating to the main trial will be authorised by the RATE-AF Trial Management Group. The results of the analysis will be published in the name of the RATE-AF Collaborative Group in a peer reviewed journal (provided that this does not conflict with the journal’s policy). Named authors must satisfy the International Committee of Medical Journal Editors (ICMJE) criteria for authorship (contribute to drafting of the article or revision for important intellectual content), provide timely approval of the final version to be published and supply detailed statements on any potential conflict of interest or financial relationship (http://www.icmje.org/). Members of the group who do not fulfil ICMJE criteria for authorship will be listed in the article appendix. Trial participants will be sent a lay summary of the final results of the trial, which will contain a reference to the full paper.
IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/07/2019
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary
2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28729311