Evaluation of Rivaroxaban for Thromboprophylaxis in Patients Undergoing Elective Unilateral Primary Hip Arthroplasty Following ERAS Protocol

The primary objective of the ENABLE-Hip Trial is to evaluate whether a reduced duration of postoperative **thromboprophylaxis** using a direct oral anticoagulant (DOAC) for 10 days is non-inferior to the standard 35-day regimen in preventing acute symptomatic venous thromboembolism (VTE) in patients undergoing elective total hip arthroplasty (THA) following the Enhanced Recovery after Surgery (ERAS) protocol. This is clinically relevant as it may reduce the duration of anticoagulation therapy without compromising patient safety, potentially minimizing the risk of bleeding and improving recovery outcomes.

Secondary objectives include assessing: - Death from any cause - Isolated symptomatic distal deep vein thrombosis (DVT) - Myocardial infarction or stroke - Need for readmission to the hospital - Length of hospital stay - Patient mobility - Changes in patient-reported hip joint-specific disability following surgery - Generic quality of life - Postoperative healthcare resource utilization - Major or clinically relevant non-major bleeding - Serious adverse events (SAEs). These objectives aim to provide a comprehensive evaluation of the intervention's impact on patient health and healthcare resource use.

The clinical trial involves **patients undergoing elective unilateral primary hip arthroplasty** who meet the criteria for Enhanced Recovery after Surgery (ERAS) based on a predefined multidisciplinary plan of care. The study population includes both male and female participants, aged between 18 and 85 years, who are scheduled for elective unilateral primary total hip arthroplasty (THA) and are eligible for perioperative management as per the ERAS protocol. Participants are required to have a baseline Timed Up and Go (TUG) test score of less than 20 seconds, indicating good mobility status before surgery. The trial includes individuals capable of understanding and complying with protocol requirements, such as having sufficient knowledge of the German language to answer questionnaires and the ability to swallow intact capsules. A negative serum pregnancy test and the use of a highly effective method of contraception are required for the duration of the study treatment. The sponsor has not provided information regarding the total number of participants. The trial population selection considers the capability to adhere to the protocol, and the study includes a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of a reduced duration of postoperative **thromboprophylaxis** using a direct oral anticoagulant (DOAC) in patients undergoing elective unilateral primary hip arthroplasty. The trial employs a **randomized**, **double-blind**, and **controlled** design to ensure the reliability and validity of the results. Participants will be randomly assigned to receive either the active treatment, **Rivaroxaban**, or a placebo, both administered in the form of hard gelatin capsules. The trial aims to compare a 10-day course of thromboprophylaxis with the standard 35-day regimen, focusing on the prevention of acute symptomatic venous thromboembolism (VTE).

The trial is expected to commence recruitment on June 30, 2024, and conclude by March 31, 2027. Participants will be involved in the study for a maximum of 90 days post-enrollment. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as age, mobility status, and ability to comply with the protocol. Following randomization, participants will attend follow-up visits to monitor for primary and secondary endpoints, including symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and other health outcomes. The end-of-study visit will assess the overall health status and any adverse events experienced during the trial.

Inclusion criteria require participants to provide written informed consent, be aged between 18 and 85 years, and meet specific health and procedural criteria, such as a baseline Timed Up and Go (TUG) test score of less than 20 seconds. Exclusion criteria are not specified in the provided data. Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial's primary endpoint is the occurrence of acute symptomatic or fatal VTE within the first 90 days, confirmed by objective testing. Secondary endpoints include overall mortality, myocardial infarction, stroke, and other health-related outcomes.

The clinical trial involves the administration of **Rivaroxaban**, an experimental medication, in the form of a **hard gelatin capsule**. Rivaroxaban is a direct oral anticoagulant (DOAC) with a chemical origin, specifically designed for thromboprophylaxis. The dosage of Rivaroxaban is set at 10 mg per day, administered orally. The maximum total dose over the treatment period is 330 mg, with a maximum treatment duration of 33 days. The trial aims to evaluate the efficacy of a reduced duration of postoperative thromboprophylaxis, specifically 10 days, in patients undergoing elective total hip arthroplasty (THA) following the Enhanced Recovery After Surgery (ERAS) protocol. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is manufactured from P-tablets (P-Tabletten weiß 7 mm Lichtenstein®) and is presented in the form of hard capsules. The placebo serves as a control to assess the non-inferiority of the reduced duration of Rivaroxaban administration compared to the standard duration of 35 days. The placebo capsules are designed to mimic the appearance and administration route of the Rivaroxaban capsules, ensuring blinding of the study participants and investigators. The placebo does not contain any active pharmaceutical ingredients and is used to maintain the integrity of the trial's double-blind design.

Efficacy in the clinical trial titled "Enhanced recovery and Abbreviated Length of Anticoagulation for Thromboprophylaxis after primary Hip Arthroplasty – the ENABLE-Hip Trial" will be assessed using both primary and secondary endpoints. The primary efficacy endpoint is the occurrence of acute symptomatic or fatal **venous thromboembolism (VTE)** within the first 90 days after enrollment. This includes symptomatic deep vein thrombosis (DVT) of the popliteal or more proximal leg veins, or symptomatic or fatal pulmonary embolism (PE), confirmed by objective testing.

Secondary endpoints include a range of clinical outcomes such as death from any cause, isolated symptomatic distal DVT, myocardial infarction or stroke, need for readmission to the hospital, length of hospital stay, serious adverse events (SAEs), patient mobility, changes in patient-reported hip joint-specific disability following surgery, generic quality of life, postoperative healthcare resource utilization, and overt major or clinically relevant non-major bleeding. These endpoints will be measured and collected at specified timepoints throughout the trial to ensure comprehensive assessment of the treatment's efficacy.