Comparative Safety and Efficacy of Apixaban Versus Warfarin in Patients with End-Stage Renal Disease on Peritoneal Dialysis and Non-Valvular Atrial Fibrillation

The primary objective of this study is to evaluate the **safety** of apixaban compared to warfarin by assessing the incidence of bleeding events in patients with end-stage renal disease on chronic peritoneal dialysis and with non-valvular atrial fibrillation. This is clinically relevant as it addresses the risk of bleeding, a significant concern in anticoagulation therapy, particularly in this patient population.

Secondary objectives include:

• Comparing the effectiveness of apixaban versus warfarin by examining the incidence of stroke.
• Evaluating other major events such as myocardial infarction and mortality.
• Investigating the pharmacodynamics of the treatments.

The clinical trial involves **patients with end-stage renal disease** on chronic peritoneal dialysis and with non-valvular atrial fibrillation. The study population includes both men and women aged 18 years and older. Participants are required to have been treated with peritoneal dialysis for at least three months and have a history of non-valvular atrial fibrillation, either currently treated with oral anticoagulation or starting such treatment. The trial includes individuals with a CHA2DS2-VASc score of 2 or higher. Women of childbearing potential must use an effective method of contraception. The trial population was selected based on these criteria, and all participants provided informed consent. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, reflecting the specific health conditions of the participants.

The clinical trial is designed to evaluate the **safety** and efficacy of **apixaban** compared to **warfarin** in patients with end-stage renal disease on chronic peritoneal dialysis and with non-valvular atrial fibrillation. This is a randomized, controlled trial with a double-blind methodology to ensure unbiased results. The trial is expected to commence on January 8, 2025, and conclude by March 31, 2027, with an estimated recruitment start date of March 31, 2024. The trial will span a total duration of 52 weeks for each participant, during which the primary endpoint will be the incidence of clinically significant major or non-major bleeding, assessed using the ISTH score as the primary measure.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, medical history, and current treatment regimen. Following randomization, participants will attend regular follow-up visits at specified intervals to monitor health status, medication adherence, and any adverse events. These visits will also include assessments of secondary endpoints such as stroke, systemic embolism, myocardial infarction, and death from any cause. The end-of-study visit will occur at the conclusion of the 12-month treatment period, where final evaluations will be conducted.

Participant involvement is expected to last for the entire 52-week treatment period unless conditions arise that necessitate early termination. Such conditions may include significant adverse reactions, withdrawal of consent, or non-compliance with study protocols. The trial aims to provide comprehensive data on the comparative safety and efficacy of the two anticoagulants, contributing valuable insights into their use in this specific patient population.

The clinical trial involves the administration of three **experimental medications**: **WARFARIN SODIUM**, **WARFARIN**, and **APIXABAN**. Each medication is provided in a **tablet** form and is administered **orally**. The trial aims to evaluate the safety and efficacy of these medications in patients with non-valvular atrial fibrillation undergoing peritoneal dialysis.

**WARFARIN SODIUM** is administered in a tablet form with a maximum daily dose of 10 mg. The treatment period for this medication is up to 52 weeks. The administration route is oral, and the medication is not a pediatric formulation. The active substance in this medication is warfarin sodium, and it is classified as a chemical medicinal product.

**WARFARIN** is also administered in a tablet form with a maximum daily dose of 10 mg, similar to warfarin sodium. The treatment duration is up to 52 weeks, and the administration route is oral. This medication is not formulated for pediatric use. The active substance is warfarin, and it is categorized as a chemical medicinal product.

**APIXABAN** is provided in a tablet form with a maximum daily dose of 5 mg. The treatment period extends up to 52 weeks, and the administration is oral. This medication is not a pediatric formulation. The active substance is apixaban, and it is identified as a chemical medicinal product.

Throughout the trial, participant compliance with the dosing schedules will be monitored to ensure adherence to the prescribed treatment regimens. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data provided.

The efficacy of the clinical trial comparing **apixaban** versus **warfarin** in patients with non-valvular atrial fibrillation undergoing peritoneal dialysis will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the incidence of clinically significant major or non-major bleeding events, evaluated using the ISTH score as the primary measure, with Gusto and TIMI scores serving as secondary measures. This assessment will occur from randomization through Month 12.

Secondary endpoints include the occurrence of stroke or systemic embolism, myocardial infarction, and death from any cause, all measured from randomization until Month 12. Additionally, the trial will monitor INR values, interpreted using the Rosendaal method, and the antiXa activity of apixaban at Months 1, 6, and 12, as well as in the event of bleeding. These parameters will provide a comprehensive evaluation of the efficacy of the treatments under investigation.