Pharmacokinetics and Pharmacodynamics of Reduced-Dose Rivaroxaban in Chronic Hemodialysis Patients Without Oral Anticoagulation Indication

The primary objective of this study is to identify the dose of **rivaroxaban** (5 mg/day, 10 mg/day, or 15 mg/day) that offers the optimal biological safety and efficacy profile, specifically in terms of pharmacokinetics and pharmacodynamics, in a population of chronic hemodialysis patients who do not have an indication for oral anticoagulation. This is clinically relevant as it aims to determine the most appropriate dosing regimen for this specific patient group, potentially improving therapeutic outcomes and minimizing adverse effects.

Secondary objectives include assessing the risk of bleeding associated with each dose of rivaroxaban according to the BARC (Bleeding Academy Research Consortium) classification in dialysis patients. This evaluation is crucial for understanding the safety profile of rivaroxaban in this vulnerable population, thereby informing clinical decision-making and enhancing patient safety.

The clinical trial involves a study population of adult patients aged 18 years and older, both **male** and **female**, who are undergoing **chronic hemodialysis** for at least three months. The total number of participants has not been disclosed by the sponsor. Participants are required to be covered by or entitled to social security and must have signed a written informed consent form. The trial does not include a vulnerable population. The study aims to identify the dose of rivaroxaban with the best biological safety and efficacy profile in this specific population, which does not have an indication for oral anticoagulation. No specific lifestyle considerations such as diet or physical activity are mentioned as part of the trial criteria.

The clinical trial is designed to evaluate the **pharmacokinetics** and **pharmacodynamics** of a reduced dose regimen of **rivaroxaban** in patients undergoing chronic hemodialysis. This Phase IV trial is structured as a randomized, double-blind, controlled study, aiming to identify the optimal dose of rivaroxaban (5 mg/day, 10 mg/day, or 15 mg/day) that offers the best biological safety and efficacy profile. The trial is expected to commence on April 1, 2024, and conclude by April 1, 2025, with a total duration of approximately 12 months.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility criteria are assessed. Key inclusion criteria include being an adult patient aged 18 years or older, undergoing chronic hemodialysis for at least three months, and having provided written informed consent. The primary endpoint of the study is the area under the AUC curve for drug dosage and anti-Xa activity for each of the three doses of rivaroxaban. Secondary endpoints include the occurrence of bleeding events graded according to the BARC classification during the study period.

Following the inclusion visit, participants will attend regular follow-up visits to monitor drug levels, safety, and efficacy. The end-of-study visit will mark the completion of the trial, where final assessments will be conducted. The expected length of participant involvement is up to three months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Xarelto**, a pharmaceutical product containing the active substance **rivaroxaban**. Xarelto is provided in the form of **film-coated tablets**, each containing 2.5 mg of rivaroxaban. The medication is administered **orally**. The trial aims to evaluate the pharmacokinetics and pharmacodynamics of rivaroxaban in patients undergoing chronic haemodialysis. The study will assess different dosing regimens, specifically 5 mg/day, 10 mg/day, or 15 mg/day, to determine the optimal dose with the best biological safety and efficacy profile. The maximum daily dose allowed in the study is 15 mg, and the treatment period is limited to a maximum of three months.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies as deemed necessary by the clinical investigators. These therapies are not specified in the trial data but are typically administered according to the standard medical practices for the patient population involved. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. The trial does not include a placebo or comparator treatment, focusing solely on the evaluation of rivaroxaban's effects in the specified patient group.

Efficacy in this clinical trial will be assessed through the evaluation of pharmacokinetics and pharmacodynamics of **rivaroxaban** in chronic hemodialysis patients. The primary endpoint for efficacy assessment is the area under the AUC curve, which measures drug dosage and anti-Xa activity for each of the three doses of rivaroxaban (5 mg/day, 10 mg/day, and 15 mg/day). This will provide insight into the biological safety and efficacy profile of the drug at different dosages.

Secondary endpoints include the occurrence of bleeding events, which will be graded according to the BARC classification during the study period. These endpoints will be measured and collected systematically throughout the trial to ensure comprehensive data analysis. The trial is designed to identify the optimal dose of rivaroxaban that offers the best balance of safety and efficacy in the specified patient population. The study is a Phase 4 clinical trial, focusing on a population of chronic hemodialysis patients who do not have an indication for oral anticoagulation, differing from the standard marketing authorizations for Xarelto®.