The Danish Warfarin-Dialysis Study - Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis (DANWARD)

Nicholas Carlson

Status and phase

Enrolling

Phase 4

Conditions

Stroke

Atrial Fibrillation and Flutter

Major Bleed

End-stage Renal Disease

Treatments

Drug: Warfarin

Study type

Interventional

Funder types

Other

Identifiers

NCT03862859

DANWARD 1.26

2018-000484-86 (EudraCT Number)

Details and patient eligibility

About

The study aims to evaluate the appropriateness of initiating oral anticoagulation for stroke risk reduction in dialysis populations with atrial fibrillation. Specifically, the study will assess the overall safety, tolerability, and efficacy of initiating treatment with Warfarin in patients with end-stage renal disease on dialysis and atrial fibrillation.

Full description

Data pertaining to the tolerability, safety, and benefit of initiating anticoagulation for stroke risk reduction in patients with end-stage renal disease and atrial fibrillation remains conflicting and insufficient. Patients on dialysis continue to be routinely excluded from randomized controlled trials, and evidence from observational studies is plausibly biased. The main objective of the following parallel-group open randomized clinical trial presents a nationwide study aimed at investigating the benefit, tolerability, and safety of initiating warfarin versus no treatment in patients with atrial fibrillation on dialysis. The anticipated results from this project will provide conclusive evidence as to the appropriateness of initiating oral anticoagulation for stroke risk reduction in dialysis populations with atrial fibrillation with direct effects on clinical management and international guidelines pertaining to these patients.

The study is planned as a multicentre, randomized, open label, parallel group trial with planned inclusion of a total of 718 patients (359 patients per arm). Dialysis-treated patients with end-stage renal disease with paroxysmal, persistent, or permanent atrial fibrillation will be enrolled and randomized to either treatment with warfarin or no treatment. Randomization with be attained using a 1:1 allocation as per a computer-generated randomization schedule stratified by gender, age by decade, and center using permuted blocks of random sizes. Study participants will be allocated to treatment in accordance with the randomization for the full duration of the trial i.e. at a minimum one year following randomization, and followed with regular monitoring for the the primary efficacy outcome of ischemic stroke or death due to ischemic or unspecified stroke and the primary safety outcome of major bleeding defined in accordance with the International Society on Thrombosis and Hemostasis definition.

Enrollment

718 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients ≥18 years on chronic dialysis due to end-stage renal disease
Non-valvular paroxysmal, persistent, or permanent atrial fibrillation OR non-treated (for >2 months) prevalent paroxysmal, persistent or permanent atrial fibrillation as documented by an electrocardiogram or an episode of ≥30 seconds on Holter monitor, or episodes ≥ 6 minutes on event recorders or any other recording device.
Competence to understand the study rationale, including potential risks and benefits associated with treatment, necessary for written informed consent.

Exclusion criteria

CHA2DS2-VASc Score ≤1
Other indications for oral anticoagulation treatment (pulmonary embolism < 6 months, deep vein thrombosis <3 months, mechanical heart valve prosthesis) irrespective of whether treatment is implemented
Ongoing dual antiplatelet treatment
Malignancy (with exception of non-melanoma skin cancer) with recent < 1 year, ongoing, or planned curative, or palliative chemo- , radiation-, and/or scheduled surgical therapy
Endoscopy with gastrointestinal ulcer <1 month
Esophageal varices
Autoimmune og genetic coagulation disorders
Congenital alactasia, Lapp Lactase deficiency or glucose-galactose malabsorption
Pending spinal tap
Cerebrovascular malformations
Arterial aneurysms
Ulcers or wounds (Wagner grad >1)
Bacterial endocarditis < 3 months
Active bleeding contraindicating anticoagulation
Any non-elective and/or non-ambulant surgery <7 days
Cerebral hemorrhage <4 weeks
Thrombocytopenia (platelet count <100 × 109/L) <30 days.
Severe liver insufficiency (spontaneous international normalized ratio >1.5) <30 days.
Known intolerance to warfarin
Use of hypericum perforatum / St. John's Wort
Uncontrolled hypertension (repeat blood pressure >180/110 mmhg) < 30 days
Uncontrolled hyperthyroidism (thyroid-stimulating hormone <0.1μIU/mL) <30 days
Pregnancy or lactation
Participation in other ongoing intervention trials adjudged to influence study outcomes