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

Официальное название

The Danish Warfarin-Dialysis Study: Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis - A Nationwide Parallel-group Open Randomized Clinical Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Warfarin
  Dose adjusted Warfarin targeting an international normalized ratio of 2-3.

Первичные конечные точки

• Primary efficacy outcome - Number of participants with transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke [Срок оценки: From randomization to end of observation - up to 4 years]
• Primary safety outcome - Number of participants with fatal or non-fatal major bleeding [Срок оценки: From randomization to end of observation - up to 4 years]

Вторичные конечные точки (7)

• Number of participants with ischemic or unspecified stroke [Срок оценки: From time of randomization to end of observation - up to 4 years]
• Number of participants with ischemic stroke [Срок оценки: From time of randomization to end of observation - up to 4 years]
• Number of participants with hemorrhagic stroke [Срок оценки: From time of randomization to end of observation - up to 4 years]
• Number of participants with ischemic or hemorrhagic stroke [Срок оценки: From time of randomization to end of observation - up to 4 years]
• Number of deaths [Срок оценки: From time of randomization to end of observation - up to 4 years]
• The combination of any non-fatal stroke and all-cause mortality [Срок оценки: From time of randomization to end of observation - up to 4 years]
• The combination of any non-fatal stroke, any non-fatal major bleeding, and all-cause mortality [Срок оценки: From time of randomization to end of observation - up to 4 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Дания · 13 центров

• Department of Nephrology, Herlev Hospital — Herlev
• Department of nephrology, Nordsjaellands Hospital — Hillerød
• Aalborg University Hosptial — Aalborg
• Aarhus University Hospital — Aarhus
• Department of Nephrology, Copenhagen University Hospital Rigshospitalet — Copenhagen
• Esbjerg and Grindsted Hospital — Esbjerg
• Holbaek Hospital — Holbæk
• Holstebro Hospital — Holstebro
• … и ещё 5 центров

Публикации

• Ballegaard ELF, Lindhard K, Lindhardt M, Peters CD, Thomsen Nielsen F, Tietze IN, Borg R, Boesby L, Bertelsen MC, Brosen JMB, Cibulskyte-Ninkovic D, Rantanen JM, Mose FH, Kampmann JD, Nielsen AS, Breinholt JK, Kofod DH, Bressendorff I, Clausen PV, Lange T, Kober L, Kamper AL, Bang CNF, Torp-Pedersen C, Hansen D, Grove EL, Gislason G, Dam Jensen J, Olesen JB, Hornum M, Rix M, Schou M, Carlson N. Pr PMID 38413147

Идентификаторы

NCT: NCT03862859 · DANWARD 1.26 · 2018-000484-86

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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