Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial

Ellen Linnea Freese Ballegaard*, Kristine Lindhard, Morten Lindhardt, Christian Daugaard Peters, Finn Thomsen Nielsen, Ida Nørager Tietze, Rikke Borg, Lene Boesby, Marianne Camilla Bertelsen, Julie Maria Bøggild Brøsen, Donata Cibulskyte-Ninkovic, Jesper Moesgaard Rantanen, Frank Holden Mose, Jan Dominik Kampmann, Alice Skovhede Nielsen, Johanne Kodal Breinholt, Dea Haagensen Kofod, Iain Bressendorff, Peter Vilhelm Clausen, Theis LangeLars Køber, Anne Lise Kamper, Casper Niels Furbo Bang, Christian Torp-Pedersen, Ditte Hansen, Erik L. Grove, Gunnar Gislason, Jens Dam Jensen, Jonas Bjerring Olesen, Mads Hornum, Marianne Rix, Morten Schou, Nicholas Carlson

*Corresponding author for this work

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Abstract

Introduction Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. Methods and analysis The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. Ethics and dissemination The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals. Trial registration numbers NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Original languageEnglish
Article numbere081961
JournalBMJ Open
Volume14
Issue number2
Number of pages7
ISSN2044-6055
DOIs
Publication statusPublished - 26. Feb 2024

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Keywords

  • Anticoagulation
  • Clinical Trial
  • Dialysis
  • End stage renal failure
  • Thromboembolism

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