Clinical trial NCT05672550: Dose-adjustment of Enoxaparin by a Bayesian Pharmacological Approach in Pediatric Kidney Transplant Recipients (OPTI-TREX)
Official title: Dose-adjustment of Enoxaparin by a Bayesian Pharmacological Approach in Pediatric Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pediatric Kidney Transplant Recipients
Keywords: Kidney transplantation
Children
Enoxaparin
Bayesian based dose
Anti-Xa activity
allograft thrombosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-01-05
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Allograft vascular thrombosis is a devastating complication in kidney 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 be inappropriate in many circumstances. 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.

Detailed description: The investigators will compare the efficacy of the Bayesian based dose versus the dose determined in a usual empirical way based on each physician's experience.

The primary endpoint is the Anti-Xa activity within the target range 28 to 30 hours after initiation of the treatment.

This is an open labelled randomized clinical trial. The randomization will proceed during the inclusion visit by the local pediatric nephrologist or intensivist just before the first enoxaparin injection, administered within 24 hours post-transplantation.

The investigators will conduct a national multicentric study with 9 inclusion centers which are all nephrology units specialized in renal transplantation.

Eligibility 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 (methyl Tetra hydro folate reductase) 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, including AME

Exclusion Criteria

1. Per-transplant technical surgical problems
2. Pre-inclusion allograft thrombosis (before randomization and enoxaparin administration)
3. Peri-operative thrombosis or uncontrolled 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
9. UFH (unfractionated heparin) treatment during renal transplantation with an anti-Xa level detectable 4-6h post administration

Primary outcomes:
measure: Anti-Xa activity within the target range
timeFrame: At 28-30 hours after initiation of treatment
Secondary outcomes:
measure: Anti-Xa outcome measurement ≥0.3 IU/ml and ≤0.6 IU/mL
timeFrame: At 28-30 hours after initiation of treatment
measure: Difference between the Anti-Xa outcome measurement and the middle of the target range
timeFrame: At 28-30 hours after initiation of treatment
measure: Absolute difference between the Anti-Xa outcome measurement and the middle of the target range
timeFrame: At 28-30 hours after initiation of treatment
measure: Precision of Anti-Xa outcome measurement to reach the middle of the target range
timeFrame: At 28-30 hours after initiation of treatment
measure: Anti-Xa activity within the target range 4-6 hours after the 2nd enoxaparin injection
timeFrame: From 28-30 hours to 7 days after initiation of treatment
measure: Anti-Xa activity ≥0.3 IU/mL and ≤0.6 IU/mL 4-6 hours after the 2nd enoxaparin injection
timeFrame: From 28-30 hours to 7 days after initiation of treatment
measure: Time to achieve a target Anti-Xa activity (0.3-0.5 IU/mL)
timeFrame: From 28-30 hours to 7 days after initiation of treatment
measure: Percentage of time within the target range
timeFrame: From 28-30 hours to 7 days after initiation of treatment
measure: Graft thrombosis
timeFrame: Up to 30 days
measure: Enoxaparin-related side effects
timeFrame: Up to 30 days
measure: Allograft bleeding
timeFrame: Up to 30 days
measure: Enoxaparin induced thrombopenia
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker - Enfants malades
state: Ile-de-France
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: La Réunion
country: France
facility: CHU Félix Guyon
city: La Réunion
country: France
facility: CHU Félix Guyon
city: Lyon
country: France
facility: Hôpital Mère Enfant
city: Lyon
country: France
facility: Hôpital Mère Enfant
city: Montpellier
country: France
facility: Hôpital de la Villeneuve
city: Montpellier
country: France
facility: Hôpital de la Villeneuve
city: Nantes
country: France
facility: Hôtel Dieu
city: Nantes
country: France
facility: Hôtel Dieu
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
city: Paris
country: France
facility: Hôpital Robert Debré
city: Paris
country: France
facility: Hôpital Robert Debré
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Toulouse
country: France
facility: Hôpital des Enfants
city: Toulouse
country: France
facility: Hôpital des Enfants
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Olivia BOYER, Pr
role: PRINCIPAL_INVESTIGATOR
References: