Safety of switching from vitamin K antagonist to non-vitamin K antagonist oral anticoagulant in frail elderly with atrial fibrillation: rationale and design of the FRAIL-AF randomised controlled trial
Joosten, Linda P T; van Doorn, Sander; Hoes, Arno W; Nierman, Melchior C; Wiersma, Nynke M; Koek, Huiberdina L; Hemels, Martin E W; Huisman, Menno V; Roes, Kit C; van den Bor, Rutger M; Buding, Wim F; Rutten, Frans H; Geersing, Geert-Jan
(2019) BMJ Open, volume 9, issue 12
(Article)
Abstract
INTRODUCTION: Clinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF). Frail elderly were under-represented in the landmark NOAC-trials, leaving a knowledge gap on the optimal anticoagulant management (VKA or NOAC) in this increasing population. The
... read more
aim of the Frail-AF (FRAIL-AF) study is to assess whether switching from international normalised ratio (INR)-guided VKA-management to a NOAC-based treatment strategy compared with continuing VKA-management is safe in frail elderly patients with AF. METHODS AND ANALYSIS: The FRAIL-AF study is a pragmatic, multicentre, open-label, randomised controlled clinical trial. Frail elderly (age ≥75 years plus a Groningen Frailty Indicator score ≥3) who receive VKA-treatment for AF in the absence of a mechanical heart valve or severe mitral valve stenosis will be randomised to switch to a NOAC-based treatment strategy or to continue INR-guided VKA-management. Patients with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m2) will be excluded from randomisation. Based on existing trial evidence in non-frail patients, we will aim to explore whether NOAC-treatment is superior to VKA-therapy in reducing major or clinically relevant non-major bleeding events. Secondary outcomes include minor bleeding, the composite of ischaemic and haemorrhagic stroke, health-related quality of life and cost-effectiveness. The follow-up period for all subjects is 12 months. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, the Netherlands and by the Central Committee on Research Involving Human Subjects, the Netherlands. All patients are asked written informed consent. Results are expected in 2022 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences. TRIAL REGISTRATION NUMBER: EudraCT: 2017-000393-11; The Netherlands Trial Registry: 6721 (FRAIL-AF study).
show less
Download/Full Text
Keywords: anticoagulation, atrial fibrillation, bleeding, elderly, frail, open-label, General Medicine
ISSN: 2044-6055
Publisher: BMJ Publishing Group
Note: Funding Information: Competing interests G-JG and FHR report unrestricted institutional grants for performing research in the field of atrial fibrillation from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer and Daiichi Sankyo. MEWH reports personal fees from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer and Daiichi Sankyo, and grants from The Netherlands Organisation for Health Research and Development (ZonMw), outside the submitted work. MVH reports grants from The Netherlands Organisation for Health Research and Development (ZonMw), Dutch Healthcare Fund and grants and personal fees from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer, Daiichi Sankyo and Aspen, outside the submitted work. All other authors (LPTJ, SvD, AWH, MCN, NMW, HLK, KCR, RMvdB and WFB) report no competing interests. Funding Information: Funding The FRAIL-AF study is mainly supported by The Netherlands Organisation for Health Research and Development (ZonMw), grant number 848015004. Furthermore, the FRAIL-AF study receives unrestricted educational grants of all four NOAC-selling pharmaceutical companies (Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer, Daiichi Sankyo) for symposia and for the development of training material. There are no restrictions to the execution of the study or the publication process by any of the subsiding parties of this study as confirmed by the Dutch Advertising Code Committee. Funding Information: The FRAIL-AF study will be conducted according to the principles of the Declaration of Helsinki29 and in accordance with Dutch law (the Medical Research Involving Human Subjects Act (WMO)).30 The protocol was approved by the Medical Research Ethics Committee of the UMC Utrecht, the Netherlands (reviewing committee), and by the Central Committee on Research Involving Human Subjects, the Netherlands (competent authority). All patients are asked written informed consent before being randomised or followed observationally. Patients’ personal data will be saved separate from baseline and follow-up data, and their privacy will be guaranteed throughout the entire study. The progress of the study, the occurrence of (serious) adverse events and finally the overall safety of the frail elderly participating in this trial will be assessed on a frequent basis by an independent data safety monitoring board. In addition, quality assurance will be guaranteed by monitoring. Results are expected in 2022 and will be disseminated through peer-reviewed publications and presentations at national and international conferences. Funding Information: Committee of the University Medical Center Utrecht, the Netherlands (reviewing committee) on 7 September 2017, and by the Central Committee on Research Involving Human Subjects, the Netherlands (competent authority) on 3 July 2017. Provenance and peer review Not commissioned; externally peer reviewed. open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. Publisher Copyright: © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
(Peer reviewed)
