DAN-WAR-D - Danish Warfarin-Dialysis Study: Safety and efficacy of warfarin in patients with atrial fibrillation on dialysis -A nationwide parallel-group open randomized clinical trial

The primary objective of the Danish Warfarin-Dialysis Study is to evaluate the **safety** and **efficacy** of warfarin in patients with **atrial fibrillation** undergoing **dialysis**. This is clinically relevant as it addresses the therapeutic management of atrial fibrillation in a population with **end-stage renal disease**, where the use of anticoagulants like warfarin is complex due to altered pharmacokinetics and increased risk of bleeding.

Secondary objectives include investigating the association between warfarin and other predefined outcomes. This will provide further insights into the broader implications of warfarin use in this specific patient group, potentially guiding clinical decision-making and optimizing patient care.

The clinical trial involves participants diagnosed with **end-stage renal disease** and **atrial fibrillation**. The study population includes both male and female subjects aged 18 years and older, who are on chronic dialysis due to end-stage renal disease. Participants have either a de novo diagnosis of non-valvular paroxysmal, persistent, or permanent atrial fibrillation, or have non-treated prevalent atrial fibrillation as documented by an electrocardiogram or other recording devices. The trial does not specifically target a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include individuals with specific medical conditions and treatment histories, but no additional lifestyle considerations such as diet or physical activity are specified.

The clinical trial is designed to evaluate the **safety** and **efficacy** of **warfarin** in patients with **atrial fibrillation** undergoing dialysis. This study is a nationwide, parallel-group, open, randomized clinical trial. The trial aims to compare the incidence of transient ischemic attacks, ischemic or unspecified strokes, or death due to these conditions between patients allocated to receive warfarin and those receiving no treatment. The trial also assesses secondary endpoints, including major bleeding events as defined by the International Society on Thrombosis and Hemostasis. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on December 31, 2022.

Participants eligible for inclusion are adults aged 18 years or older on chronic dialysis due to **end-stage renal disease** with a new diagnosis of non-valvular paroxysmal, persistent, or permanent atrial fibrillation, or those with untreated prevalent atrial fibrillation as documented by electrocardiogram or other recording devices. The study involves a series of visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits are scheduled to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will evaluate the primary and secondary endpoints and gather final data on the participants' health outcomes.

The expected duration of participant involvement in the trial is approximately three years, depending on the individual start date within the recruitment period. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial employs **Warfarin Teva 2.5 mg Tablets** administered orally, with a maximum daily dose of 10 mg. The study is not classified as a low-intervention trial due to the investigational nature of warfarin use in this specific patient population, despite its established use in other contexts.

The clinical trial involves the administration of **Warfarin Teva 2.5 mg Tablets** as the experimental medication. The active substance in this pharmaceutical product is **warfarin sodium**, a chemical compound classified under the ATC code B01AA03, indicating its role as a vitamin K-antagonist. The medication is provided in tablet form and is intended for oral administration. The maximum daily dose is set at 10 mg, with a treatment period not exceeding 100 days. The tablets are manufactured by Sun Pharmaceutical Industries Europe B.V. and are not formulated for pediatric use. The trial aims to assess the safety and efficacy of warfarin in patients with atrial fibrillation undergoing dialysis.

The efficacy of warfarin in patients with **atrial fibrillation** on dialysis will be assessed in a nationwide parallel-group open randomized clinical trial. The primary efficacy endpoint is the occurrence of any transient ischemic attack, ischemic or unspecified stroke, or death due to these conditions. This will be compared between patients allocated to receive warfarin and those receiving no treatment. Secondary efficacy endpoints include the incidence of major bleeding events, defined according to the International Society on Thrombosis and Hemostasis criteria for major bleeding in non-surgical patients. These criteria encompass major intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, intramuscular with compartment syndrome, or gastrointestinal bleeding.