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. 2024 Feb 26;14(2):e081961.
doi: 10.1136/bmjopen-2023-081961.

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  1   2 , Kristine Lindhard  3 , Morten Lindhardt  2   4 , Christian Daugaard Peters  5   6 , Finn Thomsen Nielsen  2   7 , Ida Nørager Tietze  8 , Rikke Borg  2   9 , Lene Boesby  9 , Marianne Camilla Bertelsen  10 , Julie Maria Bøggild Brøsen  10 , Donata Cibulskyte-Ninkovic  11 , Jesper Moesgaard Rantanen  12 , Frank Holden Mose  13 , Jan Dominik Kampmann  14 , Alice Skovhede Nielsen  15 , Johanne Kodal Breinholt  16 , Dea Haagensen Kofod  17   2 , Iain Bressendorff  17   3 , Peter Vilhelm Clausen  17 , Theis Lange  18 , Lars Køber  19 , Anne-Lise Kamper  17 , Casper Niels Furbo Bang  20 , Christian Torp-Pedersen  21 , Ditte Hansen  2   3 , Erik L Grove  22   23 , Gunnar Gislason  24   25 , Jens Dam Jensen  6 , Jonas Bjerring Olesen  24 , Mads Hornum  17   2 , Marianne Rix  17 , Morten Schou  2   24 , Nicholas Carlson  17
Affiliations

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 et al. BMJ Open. .

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.

Keywords: Anticoagulation; Clinical Trial; Dialysis; End stage renal failure; Thromboembolism.

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Conflict of interest statement

Competing interests: CDP has received speaker honoraria or consultancy fees from AstraZeneca and Astellas. Support for attending meetings and travel from Boehringer Ingelheim. CDP also has an ongoing collaboration with Vifor Pharma including donation of a research grant unrelated to this study. DH has received speaker and consultancy fees from AstraZeneca, GlaxoSmithKline and UCB Nordic. ELFB has received a donation of a research grant from AstraZeneca unrelated to this study. ELG has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Novo Nordisk, MSD, Lundbeck Pharma and Organon. He is an investigator in clinical studies sponsored by AstraZeneca, Idorsia or Bayer and has received unrestricted research grants from Boehringer Ingelheim. IB has received speaker honoraria from Amgen and Bayer. JBO has received speaker honoraria or consultancy fees from Bayer, Bristol-Myers Squibb, Organon and Pfizer. LB has received consultancy fees from AstraZeneca, Astellas, Vifor Pharma, Pfizer and Novartis. LK has received speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis and Novo Nordisk. MH has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Vifor and GSK within the last 3 years. ML has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and GlaxoSmithKline. NC has received speaker honoraria from AstraZeneca and Bristol-Myers Squibb. RB has received speaker honoraria or consultancy fees from AstraZeneca, Bayer and Boehringer Ingelheim. She is an investigator in clinical studies sponsored by Boehringer Ingelheim, AstraZeneca or Bayer and has received unrestricted research grants from Boehringer Ingelheim.

Figures

Figure 1
Figure 1
Study design. Eligibility is assessed in accordance with the inclusion and exclusion criteria. 1Plasma-haemoglobin, platelet count, albumin, phosphate, ionised calcium, parathyroid hormone, C reactive protein, urea nitrogen and creatinine. 2Required in all women of childbearing potential at inclusion and monthly throughout the trial. 3Last recorded INR 4SAEs/SARs will be recorded continuously with reporting of SAEs/SARs to the study sponsor within 24 hours of identification for assessment. Efficacy and safety outcomes will be registered every month in an electronic database. ESKD, end-stage kidney disease; INR, international normalised ratio; SAE, serious adverse event; SAR, serious adverse reaction.
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