Evaluation of Apixaban Versus No Anticoagulation for Thromboprophylaxis in Patients Undergoing Abdominal, Gynecologic, and Urologic Surgery

The primary objective of the study is to evaluate the benefits and risks of **thromboprophylaxis** with apixaban, an oral factor Xa inhibitor, in comparison to no anticoagulation, for patients undergoing urologic, gynecologic, and general abdominal surgery. This evaluation is conducted in the context of standard mechanical thromboprophylaxis care. The study focuses on patients who are at similar, non-high risks of venous thromboembolism (VTE) and bleeding, where the net impact of pharmacological thromboprophylaxis remains uncertain. This is clinically relevant as it aims to determine the optimal approach to prevent VTE while minimizing bleeding risks in surgical patients.

The clinical trial involves a total of **4436 participants** who are being evaluated for the benefits and risks of thromboprophylaxis with apixaban, an oral factor Xa inhibitor, in comparison to no anticoagulant therapy, both with standard mechanical thromboprophylaxis. The study population comprises **adult patients aged 18 years and older** who are undergoing urologic, gynecologic, and general abdominal surgery procedures. Both **male and female subjects** are included, and the trial does not involve a vulnerable population. Participants were selected based on their similar (and not high) risk of **venous thromboembolism** and bleeding, ensuring that the net impact of pharmacological thromboprophylaxis remains uncertain. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include obtaining informed consent and undergoing abdominal or pelvic surgery at a similar risk of VTE and bleeding.

The clinical trial is designed to evaluate the benefits and risks of thromboprophylaxis with **apixaban**, an oral factor Xa inhibitor, compared to no anticoagulation in patients undergoing urologic, gynecologic, and general abdominal surgeries. This is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial aims to assess the incidence of venous thromboembolism (VTE), including symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as safety outcomes related to bleeding events over a 90-day period. The trial is expected to commence recruitment on February 1, 2024, and conclude by December 31, 2028.

Participants will be involved in the study for a maximum of 28 days, during which they will receive the study medication or placebo. The trial includes several key visits: an initial screening visit to confirm eligibility, follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. Inclusion criteria require participants to be adults aged 18 years or older, undergoing abdominal or pelvic surgery with a similar risk profile for VTE and bleeding. The primary endpoint is the incidence of a composite outcome of VTE at 90 days, while secondary endpoints include various bleeding and safety outcomes.

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 will employ standard mechanical thromboprophylaxis for all participants, with the intervention group receiving apixaban and the control group receiving no pharmacological anticoagulation. The study's rigorous design and comprehensive follow-up aim to provide valuable insights into the net impact of pharmacological thromboprophylaxis in this patient population.

The clinical trial involves the use of **apixaban**, an oral factor Xa inhibitor, as the experimental medication. Apixaban is administered in the form of a tablet, with a pharmaceutical form code of PHF00009MIG. The dosage for this trial is set at a maximum of 5 mg per day, with the total daily dose not exceeding 5 mg. The route of administration is oral, and the medication is to be taken once daily. The treatment period for apixaban is limited to a maximum of 28 days. Apixaban is classified as an anticoagulant and is used in this study to evaluate its efficacy in thromboprophylaxis for patients undergoing general abdominal, gynecologic, and urologic surgeries.

In addition to the experimental treatment with apixaban, the study includes a comparator group that receives no anticoagulant therapy. Both groups, however, will receive standard-of-care mechanical thromboprophylaxis. This approach allows for the assessment of the benefits and risks associated with pharmacological thromboprophylaxis using apixaban compared to mechanical thromboprophylaxis alone. The trial aims to determine the net impact of apixaban in reducing the risk of venous thromboembolism (VTE) and bleeding in patients who are at a similar risk level, excluding those at high risk.

Efficacy in the clinical trial titled "Avoiding Risks of Thrombosis and bleeding in Surgery (ARTS)" will be assessed using a range of primary, secondary, and tertiary endpoints. The primary endpoint is the incidence of a composite outcome of **venous thromboembolism (VTE)**, which includes symptomatic deep vein thrombosis (DVT) and symptomatic non-fatal or fatal pulmonary embolism (PE), evaluated at 90 days post-surgery. Secondary endpoints include the incidence of symptomatic DVT and symptomatic non-fatal or fatal PE, both assessed at 90 days. Safety outcomes will also be measured, such as the incidence of major bleeding events, defined by criteria including postoperative hemoglobin levels, transfusion requirements, and bleeding leading to death, also evaluated at 90 days.

Additional tertiary outcomes will be assessed, including the incidence of VTE and major bleeding at 30 days, overall mortality, and various bleeding complications at 90 days. The trial will also evaluate the cost-effectiveness of direct oral anticoagulant (DOAC) administration, specifically with the use of apixaban, at 90 days. These efficacy parameters will be collected and analyzed at specified timepoints, primarily at 30 and 90 days post-surgery, to determine the benefits and risks of thromboprophylaxis with apixaban compared to no anticoagulation in patients undergoing general abdominal, gynecologic, and urologic surgeries.