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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 718
- 试验地点
- 13
- 主要终点
- Primary efficacy outcome - Number of participants with transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
盲法说明
None (Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
No treatment
No treatment
Treatment with Warfarin
Warfarin with dosing targeting an international normalized ratio of 2-3.
干预措施: Warfarin (Drug)
结局指标
主要结局
Primary efficacy outcome - Number of participants with transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke
时间窗: From randomization to end of observation - up to 4 years
Any transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke or death attributable to either ischemic or undefined stroke
Primary safety outcome - Number of participants with fatal or non-fatal major bleeding
时间窗: From randomization to end of observation - up to 4 years
Any major bleeding as defined in accordance with the International Society on Thrombosis and Hemostasis definition pertaining to major bleeding in non-surgical patients
次要结局
- Number of participants with ischemic or unspecified stroke(From time of randomization to end of observation - up to 4 years)
- Number of participants with hemorrhagic stroke(From time of randomization to end of observation - up to 4 years)
- The combination of any non-fatal stroke and all-cause mortality(From time of randomization to end of observation - up to 4 years)
- Number of participants with ischemic stroke(From time of randomization to end of observation - up to 4 years)
- Number of participants with ischemic or hemorrhagic stroke(From time of randomization to end of observation - up to 4 years)
- Number of deaths(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(From time of randomization to end of observation - up to 4 years)
研究者
Nicholas Carlson
Principal Investigator
Rigshospitalet, Denmark