A Randomized Controlled Trial of Dalteparin Sodium and Enoxaparin Sodium for Thromboprophylaxis in Patients Undergoing Liver Resection

The primary objective of the PREPOSTEROUS trial is to evaluate whether **perioperatively** initiated thromboprophylaxis can effectively reduce the incidence of venous thromboembolism in patients undergoing liver surgery, without increasing the risk of bleeding complications. This is clinically relevant as venous thromboembolism is a significant postoperative complication that can lead to increased morbidity and mortality. The trial compares the efficacy and safety of preoperative versus postoperative administration of thromboprophylaxis using **dalteparin sodium** and **enoxaparin sodium**, both administered via subcutaneous injection. The study aims to provide evidence on the optimal timing of thromboprophylaxis to enhance patient outcomes following liver resection.

The clinical trial involves participants undergoing **liver surgery**, with the primary objective of assessing the efficacy of perioperatively initiated thromboprophylaxis in reducing venous thromboembolism without increasing the risk of bleeding complications. The study population includes both male and female subjects, with an age range spanning from 18 to 64 years. Participants are selected based on their scheduled liver resection procedures, and the trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed as a **randomized controlled trial** to evaluate the efficacy of perioperative thromboprophylaxis in patients undergoing liver resection. The trial aims to determine whether initiating thromboprophylaxis perioperatively can reduce the incidence of **venous thromboembolism** without increasing the risk of bleeding complications. The study will involve two anti-thrombotic agents, **dalteparin sodium** and **enoxaparin sodium**, both administered via subcutaneous injection. The trial is expected to run from March 17, 2022, to February 1, 2028, with a maximum treatment period of four weeks for each participant.

Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility, which includes all patients undergoing liver resection. Following the screening, participants will be randomized to receive either preoperative or postoperative thromboprophylaxis. Subsequent follow-up visits will be scheduled to monitor the primary endpoint, which is the occurrence of venous thromboembolisms within 30 days post-surgery. Secondary endpoints include posthepatectomy hemorrhage, the Comprehensive Complication Index score, length of postoperative hospital stay, and the total amount of transfused red blood cells within the same timeframe. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events.

Participant involvement is expected to last up to four weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is categorized as a Phase IV study, indicating it is conducted after the marketing of the drugs to gather additional information on the drug's effect in a larger population. The trial is not classified as low intervention, ensuring rigorous monitoring and adherence to safety protocols throughout its duration.

The clinical trial involves the administration of **dalteparin sodium**, an anti-thrombotic agent, as an experimental medication. Dalteparin sodium is provided in a pharmaceutical form identified as PHF00231MIG. The medication is administered via **subcutaneous injection**. The maximum daily dose is 5000 IU (international units), with a total maximum dose of 140,000 IU over a treatment period of up to 4 weeks. The administration schedule is designed to ensure consistent dosing, and participant compliance is monitored throughout the trial to ensure adherence to the dosing regimen.

Another experimental medication used in the trial is **enoxaparin sodium**, also an anti-thrombotic agent. Enoxaparin sodium is similarly provided in the pharmaceutical form PHF00231MIG and is administered through subcutaneous injection. The maximum daily dose for enoxaparin sodium is 40 mg, with a total maximum dose of 1120 mg over a treatment period of up to 4 weeks. As with dalteparin sodium, the administration schedule for enoxaparin sodium is carefully structured, and participant compliance is closely monitored to maintain the integrity of the trial data.

Both medications are utilized in the context of the PREPOSTEROUS trial, which aims to evaluate the efficacy of perioperatively initiated thromboprophylaxis in reducing venous thromboembolism without increasing the risk of bleeding complications. The trial does not include any non-experimental treatments such as placebo or comparator treatments, focusing solely on the effects of the experimental medications. The trial's design ensures that all participants receive active treatment, allowing for a direct assessment of the therapeutic benefits and safety profiles of the medications under investigation.

Efficacy in the clinical trial titled "Pre- vs. postoperative thromboprophylaxis for liver resection – a prospective, multicentre, randomized controlled trial (PREPOSTEROUS trial)" will be assessed using both primary and secondary endpoints. The primary endpoint is the occurrence of **venous thromboembolisms** within 30 days following liver resection. This will be measured by the number of patients experiencing such events. Secondary endpoints include the incidence of posthepatectomy hemorrhage, classified by any grade in the ISGLS classification, the Comprehensive Complication Index score, the length of postoperative hospital stay in days, and the total amount of transfused red blood cells in units during and within 30 days from liver resection.

The efficacy parameters will be collected and analyzed at specified timepoints, primarily focusing on the 30-day period post-surgery. The trial will utilize validated scales and classifications, such as the ISGLS classification for hemorrhage and the Comprehensive Complication Index, to ensure accurate and reliable measurement of outcomes. The data collection will be conducted in a systematic manner to facilitate robust analysis and interpretation of the efficacy of perioperatively initiated thromboprophylaxis in reducing venous thromboembolism without increasing the risk of bleeding complications.