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Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study
  1. Holger Reinecke1,
  2. Sabine Jürgensmeyer2,
  3. Christiane Engelbertz1,
  4. Joachim Gerss3,
  5. Paulus Kirchhof2,4,
  6. Günter Breithardt1,
  7. Rupert Bauersachs5,6,
  8. Christoph Wanner7
  1. 1 Dept. of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Cardiol, Muenster, Germany
  2. 2 Atrial Fibrillation NETwork, Muenster, Germany
  3. 3 Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany
  4. 4 Institute of Cardiovascular Sciences, University of Birmingham, and SWBH and UHB NHS Trusts, Birmingham, UK
  5. 5 Department of Vascular Medicine, Klinikum Darmstadt, Darmstadt, Germany
  6. 6 Center for Thrombosis and Hemostasis, University Medical Center of Johannes Gutenberg University of Mainz, Mainz, Germany
  7. 7 Department of Medicine, Division of Nephrology, Wuerzburg University Clinic, Wuerzburg, Germany
  1. Correspondence to Professor Holger Reinecke; holger.reinecke{at}ukmuenster.de

Abstract

Introduction Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal anticoagulation in patients with AF on haemodialysis are not available. The randomised controlled phase IIIb AXADIA–AFNET 8 trial will evaluate the safety and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring haemodialysis.

Methods and analysis A total of 222 patients will be randomised in an open-labelled, 1:1 design to receive either apixaban 2.5 mg twice daily or dose-adjusted vitamin K antagonist therapy (target international normalised ratio 2.0–3.0). All patients will be treated and followed up for a minimum of 6 months up to a maximum of 24 months. The primary outcome is major or clinically relevant, non-major bleedings or death of any cause. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, thus exploring the efficacy of apixaban. The first patient was randomised in June 2017.

Ethics and dissemination The study protocol was approved by the Ethical Committee of the Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598 f-A). Written informed consent will be obtained from all patients prior to study participation, including their consent for long-term follow-up. AXADIA–AFNET 8 is an investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer, Berlin, Germany, to the participating centres, at research conferences and in peer-reviewed journals.

Trial registration numbers NCT02933697,Pre-results.

  • arial fibrillation
  • hemodialysis
  • cardiovascular morbidity
  • cardiovascular mortality
  • anticoagulation

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/.

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Footnotes

  • Contributors HR, CW, RB, PK and GB conceived and designed the study; HR, CW, RB, PK, GB and SJ contributed to protocol development; JG contributed to the statistical analysis; HR, CE and SJ participated in the writing of the manuscript; all authors critically reviewed the manuscript and approved the final version.

  • Funding This investigator-initiated trial is conducted by the Kompetenznetz Vorhofflimmern e.V. (Atrial Fibrillation NETwork), Mendelstr. 11, 48149 Muenster, Germany. The study is financed by Bristol-Myers Squibb (BMS), Munich, Germany, and Pfizer, Berlin, Germany.

  • Competing interests HR has received speaker honoraria from BMS, MedUpdate, NephroUpdate, and Pfizer. He has acted as a consultant for BMS, Pfizer and Pluristem receiving in part also financial compensations for this work. He has received research grants from the German Federal Ministry for Education and Research (BMBF). His division within the University Hospital of Muenster has taken or is still taking part in multicentre trials of BARD, Bayer, BIOTRONIK, and Pluristem receiving patient fees and financial compensation for these efforts. PK has received grants and non-financial support from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Centre for Cardiovascular Research and from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies. He is listed as inventor on two patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). During preparation of this trial, GB has received speaker honoraria from BMS and Pfizer, he has been a member of the Scientific Advisory Boards for BMS and Pfizer, and Bayer Health Care. During his chairmanship of the Atrial Fibrillation NETwork, this institution has received funding for investigator-initiated trials from various companies (for details, please consult http://www.kompetenznetz-vorhofflimmern.de/en/research). RB has received consulting / lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. CW does not report conflicts of interest in respect to the present work. Outside this area of research he has received speaker honoraria from Amgen, Boehringer-Ingelheim, Genzyme-Sanofi and Shire.

  • Patient consent Not required.

  • Ethics approval Ethical Committee of the Landesaerztekammer (Medical Association) Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598-f-A)

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

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