Rate control therapy evaluation in atrial fibrillation

ISRCTN ISRCTN95259705
DOI https://doi.org/10.1186/ISRCTN95259705
EudraCT/CTIS number 2015-005043-13
ClinicalTrials.gov number NCT02391337
Secondary identifying numbers 32563
Submission date
28/11/2016
Registration date
29/11/2016
Last edited
25/01/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

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, symptoms of breathlessness, and ability to provide written, informed consent.

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, Sandwell and West Midlands Hospital and Heartlands Hospital and takes place at general practitioners' practices in the Birmingham area (UK)

When is the study starting and how long is it expected to run for?
March 2016 to December 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

Study website

Contact information

Dr Dipak Kotecha
Scientific

Institute of Cardiovascular Sciences
University of Birmingham
Medical School
Vincent Drive
Birmingham
B15 2TT
United Kingdom

ORCiD logoORCID ID 0000-0002-2570-9812
Phone +44 (0)7974 115676
Email rate-af@trials.bham.ac.uk

Study information

Study designRandomised; Interventional; Design type: Treatment, Process of Care, Drug
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleEvaluating 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)
Study acronymRATE-AF
Study objectivesThe 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(s)East Midlands - Derby Research Ethics Committee, 18/07/2016, ref: 16/EM/0178
Health condition(s) or problem(s) studiedSpecialty: Cardiovascular disease, Primary sub-specialty: Other; UKCRC code/ Disease: Cardiovascular/ Other forms of heart disease
InterventionParticipants 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 typeOther
Primary outcome measurePatient-reported quality of life is measured using the SF-36 physical component summary score at baseline and 6 months
Secondary outcome measures1. 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 study start date23/03/2016
Completion date31/12/2019

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participantsPlanned Sample Size: 160; UK Sample Size: 160
Total final enrolment160
Key inclusion criteria1. 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
Key exclusion criteriaCurrent exclusion criteria as of 22/06/2018:
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. History of second or third-degree heart block
5. Supraventricular arrhythmias associated with accessory conducting pathways (e.g. Wolff-Parkinson-White syndrome) or a history of ventricular tachycardia or fibrillation
6. Decompensated heart failure (evidenced by need for intravenous inotropes, vasodilators or diuretics) within 14 days prior to randomisation
7. A current diagnosis of obstructive hypertrophic cardiomyopathy, myocarditis or constrictive pericarditis
8. Received or on waiting list for heart transplantation
9. Receiving renal replacement therapy
10. Major surgery, including thoracic or cardiac surgery, within 3 months of randomisation
11. Severe, concomitant non-cardiovascular disease (including malignancy) that is expected to reduce life expectancy

Previous 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
Date of first enrolment05/12/2016
Date of final enrolment02/10/2018

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

Queen Elizabeth Hospital
University Hospital Birmingham NHS Trust
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
City Hospital
Sandwell and West Birmingham Hospitals NHS Trust
Dudley Road
Birmingham
B18 7QH
United Kingdom
Sandwell General Hospital
Sandwell and West Birmingham Hospitals
Lyndon
West Bromwich
B71 4HJ
United Kingdom
Birmingham Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Sponsor information

University of Birmingham
Hospital/treatment centre

Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Phone +44 (0)121 414 8165
Email researchgovernance@contacts.bham.ac.uk
ROR logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Government

National Institute for Health Research
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 date31/12/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planThe 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 planThe current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 20/07/2017 Yes No
Results article results 02/12/2020 25/01/2021 Yes No
HRA research summary 28/06/2023 No No

Editorial Notes

25/01/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
06/10/2020: The intention to publish date has been changed from 31/01/2020 to 31/12/2020.
04/07/2019: ClinicalTrials.gov number added.
11/10/2018: The recruitment end date has been changed from 31/07/2018 to 02/10/2018.
22/06/2018: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2018 to 31/07/2018.
2. Birmingham Heartlands Hospital has been added as a trial centre.
3. The intention to publish date has been changed from 31/07/2019 to 31/01/2020.
4. The overall trial end date has been changed from 31/08/2019 to 31/12/2019.
5. The participant exclusion criteria have been changed.
6. The plain English summary has been updated to reflect the above changes.
25/07/2017: Publication reference added.