Evaluation of Individualized Thrombosis Prophylaxis with Apixaban, Nadroparin Calcium, and Dabigatran in Patients Undergoing Total Hip or Knee Arthroplasty

The primary objective of this study is to evaluate the effectiveness and safety of different **thrombosis prophylaxis** strategies in preventing symptomatic **venous thromboembolism (VTE)** in patients undergoing total knee and hip arthroplasty. This includes assessing whether in-hospital thrombosis prophylaxis alone is as effective as the standard approach in patients with low VTE risk, determining the incidence of symptomatic VTE in patients with intermediate VTE risk, and comparing the effectiveness and safety of intensified thrombosis prophylaxis versus the standard approach in patients with high VTE risk. These objectives are clinically relevant as they aim to optimize thrombosis prevention strategies, potentially reducing the risk of VTE and associated complications in surgical patients.

Secondary objectives include: - Comparing the risks of clinically relevant non-major bleeds between the targeted thrombosis prophylaxis approach and the standard approach. - Evaluating the cost-effectiveness of the targeted approach compared to the standard approach. - Determining the incidence of prosthetic joint infection, overall and in subgroups. - Comparing patient-reported outcome measures between the targeted and standard approaches. - Investigating the effect of VTE, bleeding, and prosthetic joint infections on functional outcomes after total hip and knee arthroplasty. - Determining the incidence of myocardial infarction, stroke, and death overall and in subgroups.

The clinical trial focuses on patients undergoing elective **Total Hip Arthroplasty** or **Total Knee Arthroplasty** to assess the effectiveness of thrombosis prophylaxis in preventing symptomatic **Venous Thromboembolism** (VTE). The study population includes both male and female participants aged 18 years and older. The trial does not involve a vulnerable population. Participants were selected based on their scheduled surgical procedures and their risk level for VTE. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria include being scheduled for the specified surgeries and meeting the age requirement. The trial aims to compare different prophylaxis approaches in patients with varying VTE risk levels.

The clinical trial is designed to evaluate the efficacy and safety of various **anticoagulants** in preventing symptomatic **venous thromboembolism** (VTE) in patients undergoing elective total hip or knee arthroplasty. This is a national, multicenter, randomized, multi-arm, open-label trial. The trial aims to compare different thrombosis prophylaxis strategies based on the patient's VTE risk level. The trial is expected to commence recruitment on September 1, 2024, and conclude by February 1, 2030.

Participants will be randomly assigned to receive one of the following treatments: **apixaban**, **nadroparin calcium**, **dabigatran**, **dalteparin sodium**, **enoxaparin sodium**, **rivaroxaban**, or **andexanet alfa**. The trial will include a screening visit to confirm eligibility, followed by treatment initiation. The primary endpoints are the number of VTEs and major bleeds within the first three months postoperatively. Secondary endpoints include clinically relevant non-major bleeding, impact on quality-adjusted life years (QALYs), healthcare costs, prosthetic joint infections, patient-reported outcomes, myocardial infarction, ischemic stroke, and death.

Participants will be involved in the study for a maximum of 40 days, depending on the treatment arm. The study includes regular follow-up visits to monitor safety and efficacy outcomes. An end-of-study visit will be conducted to assess the final outcomes and gather data on any adverse events. Conditions that may lead to early termination from the study include significant adverse reactions, non-compliance with the study protocol, or withdrawal of consent by the participant.

The clinical trial involves the administration of several **anticoagulant** medications, each with specific pharmaceutical forms, dosages, and routes of administration. **Apixaban** is provided in the form of a film-coated tablet and is administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 400 mg over a treatment period of up to 40 days. The dosing frequency is determined based on the specific needs of the trial protocol.

**Nadroparin Calcium** is administered as a solution for injection in a pre-filled syringe via subcutaneous injection. The maximum daily dose is 5700 IU, with a total maximum dose of 159600 IU over a treatment period of up to 4 weeks. This medication is used as a comparator in the trial.

**Dabigatran** is provided in capsule form and administered orally. The maximum daily dose is 220 mg, with a total maximum dose of 6160 mg over a treatment period of up to 4 weeks. This medication serves as a comparator in the study.

**Cofact** is available as a solution for injection and is administered via infusion. It contains a combination of human coagulation factors IX, II, VII, and X, along with proteins C and S. The maximum daily dose is 2500 U, with a total maximum dose of 2500 U, administered over a single day. This product is used as an auxiliary treatment in the trial.

**Dalteparin Sodium** is administered as a solution for injection in a pre-filled syringe via subcutaneous injection. The maximum daily dose is 2500 IU, with a total maximum dose of 70000 IU over a treatment period of up to 4 weeks. This medication is used as a comparator in the trial.

**Enoxaparin Sodium** is also administered as a solution for injection in a pre-filled syringe via subcutaneous injection. The maximum daily dose is 4000 IU, with a total maximum dose of 112000 IU over a treatment period of up to 4 weeks. This medication serves as a comparator in the study.

**Andexanet Alfa** is provided as a lyophilized powder for preparation for injection and is administered via infusion. The maximum daily dose is 1760 mg, with a total maximum dose of 1760 mg, administered over a single day. This product is used as an antidote in the trial.

**Rivaroxaban** is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 280 mg over a treatment period of up to 4 weeks. This medication is used as a comparator in the trial.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to evaluate the efficacy and safety of these treatments in preventing symptomatic venous thromboembolism (VTE) in patients undergoing total knee and hip arthroplasty, with varying levels of VTE risk.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the number of **Venous Thromboembolisms (VTEs)** and major bleeding events occurring within the first three months postoperatively. These endpoints are critical in evaluating the effectiveness of thrombosis prophylaxis strategies in patients undergoing total knee and hip arthroplasty.

Secondary endpoints will provide additional insights into the trial's outcomes. These include clinically relevant non-major bleeding, the impact of events on Quality-Adjusted Life Years (QALYs), healthcare costs, prosthetic joint infections, patient-reported outcome measures, myocardial infarction, ischemic stroke, and death. These parameters will be measured and collected at specified intervals throughout the trial duration, allowing for a comprehensive analysis of the prophylaxis strategies' efficacy and safety.