Comparison of Hemorrhagic Risk in Acute Venous Thromboembolism Treatment with Rivaroxaban Versus Apixaban

The primary objective of this study is to compare the **safety** of **apixaban** and **rivaroxaban** in the treatment of **acute venous thromboembolism** (VTE). This comparison is clinically relevant as it aims to evaluate the bleeding risk associated with these two antithrombotic agents, which are commonly used in the management of VTE. Understanding the safety profile of these medications is crucial for optimizing patient outcomes and minimizing adverse events related to bleeding.

The clinical trial investigating the safety of apixaban and rivaroxaban for the treatment of **Acute Venous Thromboembolism** includes a total of 2736 participants. The study population comprises both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants were selected based on the presence of symptomatic acute venous thromboembolism, specifically proximal lower extremity deep vein thrombosis or segmental or greater pulmonary embolism. All participants were required to provide informed consent, demonstrating the ability to understand the Patient Information Leaflet and sign the consent form. Women of childbearing potential were required to use effective contraception and present a negative urine pregnancy test at the initial visit. The trial does not specify any particular lifestyle considerations such as diet or physical activity for the participants.

The clinical trial is designed to evaluate the safety of **apixaban** and **rivaroxaban** in the treatment of **acute venous thromboembolism**. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment is being administered, thereby minimizing bias. The trial is expected to last until September 30, 2024, with recruitment having commenced on June 1, 2023. Participants will be involved in the study for a maximum treatment period of three months, during which they will receive either Xarelto (15 mg or 20 mg film-coated tablets) or Eliquis (5 mg film-coated tablets) orally.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is assessed based on criteria such as symptomatic acute VTE, age of 18 years or older, and the ability to provide informed consent. Women of childbearing potential must use effective contraception and have a negative urine pregnancy test at Visit 1. Follow-up visits will be scheduled to monitor the participants' health, adherence to medication, and any adverse events. The primary endpoint is the rate of adjudicated clinically relevant bleeding events, including major bleeding and clinically relevant non-major bleeding. Secondary endpoints include adjudicated major bleeding events, recurrent VTE events, VTE-related deaths, all-cause mortality, medication adherence, and cost-effectiveness ratios.

The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted. Participants may be terminated early from the study if they experience significant adverse events, withdraw consent, or fail to comply with the study protocol. The trial is categorized as Phase 4, involving marketed drugs under approved conditions of use, and is not considered low intervention. The study aims to provide valuable insights into the comparative safety profiles of these antithrombotic agents in a real-world setting.

The clinical trial involves the administration of **Xarelto 15 mg film-coated tablets**, which contain the active substance **rivaroxaban**. This medication is an antithrombotic agent, chemically derived, and is manufactured by Bayer AG. The pharmaceutical form is a film-coated tablet, intended for oral administration. The maximum daily dose is 30 mg, with a total maximum dose of 2430 mg over a treatment period of up to 3 months. Participants are required to take the medication as prescribed, with compliance monitored throughout the study.

Another experimental medication used in the trial is **Eliquis 5 mg film-coated tablets**, containing the active substance **apixaban**. This antithrombotic agent is also chemically derived and is produced by Bristol-Myers Squibb/Pfizer EEIG. The pharmaceutical form is a film-coated tablet, administered orally. The maximum daily dose is 20 mg, with a total maximum dose of 1040 mg over a treatment period of up to 3 months. Participant adherence to the dosing schedule is closely monitored to ensure accurate data collection.

The trial also includes the use of **Xarelto 20 mg film-coated tablets**, which, like the 15 mg formulation, contain **rivaroxaban** as the active substance. This medication is similarly an antithrombotic agent, chemically derived, and manufactured by Bayer AG. The pharmaceutical form is a film-coated tablet for oral administration. The maximum daily dose is 30 mg, with a total maximum dose of 2430 mg over a treatment period of up to 3 months. Compliance with the dosing regimen is essential and is monitored throughout the trial.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of acute venous thromboembolism (VTE) with **rivaroxaban** and **apixaban**. The primary endpoint is the rate of adjudicated clinically relevant bleeding (CRB) events, which is defined as the composite of major bleeding (MB) events and/or clinically relevant non-major bleeding events (CRNMB). Secondary endpoints include adjudicated MB events, adjudicated CRNMB events, adjudicated recurrent VTE events, adjudicated VTE-related deaths, all-cause mortality, medication adherence, and incremental cost-effectiveness ratios. These ratios will consider the cost per one CRB case prevented, cost per one life year saved, and cost per one quality-adjusted life year (QALY) gained. Additionally, the impact of verbal consent on patient participation will be compared with participants from sites using written informed consent.