Dose Adjustment of Enoxaparin Sodium via Bayesian Pharmacological Approach in Pediatric Renal Transplant Recipients with Allograft Vascular Thrombosis

The primary objective of the study is to **optimize the dose of enoxaparin** in pediatric renal transplant recipients to achieve appropriate anti-Xa activity. This is clinically relevant as it aims to prevent **allograft vascular thrombosis**, a serious complication that can compromise the success of the transplant. The study focuses on dose-adjustment using a Bayesian pharmacological approach, which is expected to enhance the precision of anticoagulation therapy in this vulnerable population.

The clinical trial focuses on **pediatric renal transplant** recipients, specifically targeting a vulnerable population aged between 2 and 18 years. Both male and female subjects are included in the study. Participants are required to have an indication for enoxaparin treatment within the first week post-transplant, as determined by the local transplant team. This may include conditions such as inherited or acquired thrombotic disorders, a history of thrombosis, or specific donor and recipient age criteria. The trial population was selected based on these medical indications, and all participants must have a signed informed consent form from their legal guardians and be affiliated with a health insurance system. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the **dose-adjustment** of **enoxaparin sodium** in pediatric renal transplant recipients to achieve optimal anti-Xa activity. This study is a multicenter, randomized, open-label, phase III trial comparing two treatment arms. The trial aims to optimize the dose of enoxaparin to ensure appropriate anti-Xa activity in children who have undergone renal transplantation. The trial is expected to commence recruitment on June 28, 2023, and conclude by July 28, 2025.

Participants will be pediatric renal transplant recipients aged between 2 and 18 years, with an indication for enoxaparin treatment in the first post-transplant week. The inclusion criteria require informed consent from legal guardians and affiliation with a health insurance system. The primary endpoint is achieving anti-Xa activity within the target range of 0.3 to 0.5 IU/mL, measured 28-30 hours after treatment initiation.

The trial will involve several study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Following the screening, participants will undergo regular follow-up visits to monitor anti-Xa activity and adjust the enoxaparin dose as necessary. The end-of-study visit will assess the overall treatment efficacy and safety. The maximum treatment period with enoxaparin is seven days, with a maximum daily dose of 100 IU/kg and a total dose not exceeding 700 IU/kg.

Participant involvement is expected to last for the duration of the treatment period, with additional time for follow-up assessments. Conditions that may lead to early termination from the study include adverse reactions to enoxaparin or withdrawal of consent by the legal guardians. The trial will adhere to rigorous scientific and ethical standards to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **enoxaparin sodium**, a low molecular weight heparin, as the experimental medication. Enoxaparin sodium is provided in a pharmaceutical form identified by the code PHF00231MIG. The medication is administered via **subcutaneous use**. The dosing regimen is based on a weight-adjusted approach, with a maximum daily dose of 100 IU/kg and a maximum total dose of 700 IU/kg over a treatment period of up to 7 days. The primary objective is to optimize the dose to achieve appropriate anti-Xa activity in pediatric renal transplantation patients. The formulation used in this trial is not specifically designed for pediatric use, and the product is classified as a biological medicinal product.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the dose-adjustment of enoxaparin sodium using a Bayesian pharmacological approach. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not involve any additional devices or substances, and the enoxaparin sodium used is not classified as an orphan drug.

Efficacy in the clinical trial titled "OPTI-TREX - Dose-adjustment of enoxaparin by a bayesian pharmacological approach in pediatric renal transplant recipients" will be assessed primarily through the measurement of **anti-Xa activity**. The primary endpoint is defined as achieving anti-Xa activity within the target range, specifically between 0.3 IU/mL and 0.5 IU/mL, 28-30 hours after the initiation of treatment. This parameter will be used to determine the success of the dose optimization of enoxaparin in pediatric renal transplantation patients. The trial aims to optimize the dose of enoxaparin to achieve appropriate anti-Xa activity, which is crucial for the prevention of thrombotic events in this patient population.