Dose-adjustment of Enoxaparin by a Bayesian Pharmacological Approach in Pediatric Renal Transplant Recipients (OPTI-TREX)

• Status: Not yet recruiting
• Trial end date: 2025-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Allograft vascular thrombosis is a devastating complication in renal transplantation in adults and older children. Though uncommon, it is often irreversible and represents the main cause of graft loss within after kidney transplantation in adults and in the first post-operative year in children. Since allograft thrombosis is usually observed in the first 48h post-operatively, the need to promptly achieve appropriate anticoagulation in at-risk patients is of utmost importance.

However, no consensus exists regarding the optimal prophylaxis in the peri-transplant period and the following dose-adjustment, and practices are highly heterogeneous among centers. Moreover, the therapeutic target is very narrow and antithrombotic agents may conversely increase the risk of allograft hematoma. Enoxaparin is a low molecular weight heparin commonly used in this context, but off-label in children. Therapeutic ranges are based on anti-Xa levels 4 to 6 hours following injection and extrapolated from adults although evidences suggest that such extrapolation may, in many circumstances, be inappropriate. The current pediatric practice of dose adjustment to achieve and maintain a target anti-Xa range is empirical and dependent on the physician.

The aim of the proposed clinical trial is to assess the efficacy/safety profile of this bayesian-based dose optimization in the clinical setting, as compared to the current practices of empirical adjustment. This should greatly improve the personalized management of renal transplanted children, a subset of patients with singular renal function and little-investigated pharmacokinetics and help standardizing and rationalizing practices.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Enoxaparin; Enoxaparin sodium

Criteria

Inclusion Criteria:

1. Pediatric renal transplant recipients

2. Aged ≥ 2 years and <18 years

3. With an indication for enoxaparin treatment in the first post-transplant week according to the local transplant team such as inherited or acquired thrombotic disorders (eg. but not exclusive protein C, protein S, and antithrombin III deficiency; factor V Leiden mutation (FV506Q), prothrombin mutation (G20210A), mutation in the MTHFR (méthyl Tétra hydro folate réductase) gene (C677T), and antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants), history of thrombosis, donor age < 2 years, recipient age < 5 years, cold ischemia time >24h, multiple renal vessels.

4. Informed consent form signed by the legal guardian(s)

5. Affiliated to a health insurance system

Exclusion Criteria

1. Per-transplant technical surgical problems

2. Pre-inclusion allograft thrombosis (before randomization and enoxaparin administration)

3. Peri-operative thrombosis or bleeding (before randomization and enoxaparin administration)

4. Peri-operative hemodynamic instability

5. Medical history of heparin-induced thrombocytopenia

6. Allergic reaction to enoxaparin or excipients

7. Pregnancy

8. LMWH (Low molecular weight heparins) prophylactic before transplant