NCT Number: NCT05672550
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.
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Notify Me2 year–20 year
All sexes
Interventional
Phase 4
Hôpital Necker - Enfants malades, Paris, Île-de-France Region, France
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
A first recommended dose of enoxaparin 50 IU/kg subcutaneously is administered during transplantation or within the first 24 hours.
Then a Bayesian estimate of individual pharmacokinetics is performed to adapt the next twice daily (Hour 12;Hour 24) enoxaparin dose until achievement of the target on two consecutive measurements. Then anti-Xa activity will be evaluated once a day until day 7.
A first recommended dose of enoxaparin 50 IU/kg is administered during transplantation or within the first 24 hours. Then anti-Xa activity is measured and twice-daily (hour 12 ; hour 24) enoxaparin empirical dose-adjustment is performed according to the usual practices in the investigating centers to target.
Time frame: At 28-30 hours after initiation of treatment
Anti-Xa activity within the target range (i.e., success defined by an anti-Xa activity ≥0.3 IU/mL and ≤0.5 IU/mL).
Time frame: At 28-30 hours after initiation of treatment
Anti-Xa outcome measurement is defined as: Anti-Xa activity 4-6 hours after the first enoxaparin injection on day 2
Time frame: At 28-30 hours after initiation of treatment
Anti-Xa outcome measurement is defined as: Anti-Xa activity 4-6 hours after the first enoxaparin injection on day 2- the middle of the target range = 0.4UI/mL
Time frame: At 28-30 hours after initiation of treatment
Anti-Xa outcome measurement is defined as: Anti-Xa activity 4-6 hours after the first enoxaparin injection on day 2 - middle of the target range = 0.4UI/mL
Time frame: At 28-30 hours after initiation of treatment
Precision (Root Mean square Error) - middle of the target range = 0.4 UI/mL
Time frame: From 28-30 hours to 7 days after initiation of treatment
Anti-Xa activity ≥0.3 IU/mL and ≤0.5 IU/mL
Time frame: From 28-30 hours to 7 days after initiation of treatment
Anti-Xa activity ≥0.3 IU/mL and ≤0.6 IU/mL
Time frame: From 28-30 hours to 7 days after initiation of treatment
Time will be defined by the delay between date and time of treatment initiation and date and time of anti-Xa activity measurement in the target range.
Time frame: From 28-30 hours to 7 days after initiation of treatment
The target range is defined as anti-Xa activity ≥0.3 IU/ml and ≤0.5 IU/mL from treatment initiation to D7 derived with individual predicted concentration time course
Time frame: Up to 30 days
Graft thrombosis : assessed by allograft ultrasound
Time frame: Up to 30 days
Enoxaparin-related side effects during the first postoperative month: bleeding (all localisations), graft hematoma (presence/absence): assessed by ultrasound
Time frame: Up to 30 days
Allograft bleeding: bleeding with post-operative transfusion
Time frame: Up to 30 days
Thrombopenia
Assistance Publique - Hôpitaux de Paris
Other
Dose-adjustment of Enoxaparin by a Bayesian Pharmacological Approach in Pediatric Kidney Transplant Recipients
Acronym: OPTI-TREX
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
