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Cardiovascular medicine
Protocol
A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial
  1. Dipak Kotecha1,2,3,4,
  2. Melanie Calvert4,5,
  3. Jonathan J Deeks5,6,
  4. Michael Griffith2,
  5. Paulus Kirchhof1,2,3,4,
  6. Gregory YH Lip1,3,4,
  7. Samir Mehta6,
  8. Gemma Slinn6,
  9. Mary Stanbury7,
  10. Richard P Steeds1,2,
  11. Jonathan N Townend1,2
  1. 1 Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
  2. 2 Cardiology, University Hospitals Birmingham NHS Trust, Birmingham, UK
  3. 3 Cardiology, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK
  4. 4 Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
  5. 5 Institute of Applied Health Research, University of Birmingham, Birmingham, UK
  6. 6 Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
  7. 7 (Lead for the Patient and Public Involvement panel), Birmingham, UK
  1. Correspondence to Dr. Dipak Kotecha; d.kotecha{at}bham.ac.uk

Abstract

Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being.

Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF.

Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice.

Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF.

Ethics and dissemination East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications.

Trial registration Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results.

  • atrial fibrillation
  • heart rate
  • quality of life
  • Echocardiography
  • Protocols & guidelines
  • RATE-AF

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/bmjopen-2016-015099

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    Footnotes

    • DK is the Chief Investigator

    • Contributors The manuscript was drafted by DK who is the Chief Investigator for the RATE-AF trial. MG and GYHL are Principal Investigators. MC, PK, RPS and JNT are members of the Trial Management Group. JJD, SM and GS are representatives from the Clinical Trials Unit. MS is the Lead for the Patient Involvement Panel, and a member of the Steering Committee. All authors contributed to the writing of the RATE-AF protocol or patient information, and edited this manuscript for intellectual content.

    • Funding DK and the RATE-AF trial are supported by the National Institute of Health Research (NIHR) as part of a Career Development Fellowship (CDF-2015-08-074). The opinions expressed in this paper are those of the authors and do not represent the NIHR or the UK Department of Health.

    • Competing interests None of the authors report a conflict of interest. All authors have completed the ICMJE uniform disclosure form (www.icmje.org/coi_disclosure.pdf) and declare: DK reports grants from Menarini, during the conduct of the study; non-financial support from Daiichi Sankyo and personal fees from AtriCure, outside the submitted work. MC reports grants from the National Institute of Health Research, during the conduct of the study; and personal fees from Astella Pharma and Ferring Pharma, outside the submitted work. PK reports consulting fees and honoraria from Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Medtronic, Pfizer and Servier, all outside the submitted work; research grants from Bristol-Myers Squibb, Pfizer, Cardiovascular Therapeutics, Daiichi Sankyo, Sanofi, St. Jude Medical, German Federal Ministry for Education and Research (BMBF), Fondation Leducq, German Research Foundation (DFG), European Union, British Heart Foundation and Medical Research Council UK, all outside the submitted work; and is listed on two patent applications on AF therapy and markers for AF, both outside the submitted work. GYHL has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Biotronik, Portola and Boehringer Ingelheim, and has been on the speaker's bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim and Sanofi Aventis. RPS is the President of the British Society of Echocardiography. JJD, MG, MS. JNT, SM, GS report no competing interests.

    • Patient consent Informed written consent was obtained from all trial participants using HRA and ethics-approved consent forms.

    • Ethics approval East Midlands-Derby Research Ethics Committee (16/EM/0178).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Correction notice This article has been corrected since it first published. The acronym for the Chief Investigator has been corrected. The Funding information has been updated with the correct ID of the Career Development Fellowship. Other typos and encoding errors have been corrected in the abstract, main text and reference list.