Clinical trial NCT02337036: Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients
Official title: Building a Population Pharmacokinetic Model of Tacrolimus in Paediatric Liver Transplant Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Transplantation, Child
Keywords: Liver transplantation
Child
Tacrolimus
Pharmacokinetic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
First posted: 2015-01-13
Enrollment: 80
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. This study is designed to assess the posology of tacrolimus in post-transplantation in the month after liver transplantation to obtain a therapeutic target between 10-15 ng/mL and the impact of biological and genetic factors on the pharmacokinetic parameters in paediatric liver transplant recipients.

Detailed description: Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. Therapeutic drug monitoring (TDM) of tacrolimus, based on whole-blood trough concentration (C0) values, is mandatory for use of twice-daily tacrolimus (Prograf_) as in order to decrease interindividual variability in exposure and thereby minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).

Until now, the C0 is the easiest means of individual dose adjustment, as only one blood sample is required and the clinician can easily calculate the dose needed to reach the target. Many factors have an impact on the pharmacokinetic parameters. However the adaptation of the time to achieve the target stays an issue. Among factors of inter and intra variability of pharmacokinetic of tacrolimus, some of them are specific of the pediatric liver transplantation population.

Aims: To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.

Eligibility criteria: Inclusion Criteria:

* Age of children who need to have a liver transplantation : between 6 month and 12 years
* Formulary of consent signed by the two parents.
* Children who need to receive tacrolimus per os (Modigraf® ) only after liver transplantation associated to Simulect® (basilixumab) in post-transplantation immediately as main
* Affiliation to the system of social protection.

Exclusion Criteria:

* Children who need a multi organs transplantation
* Hypersensibility or Contraindication to Modigraf® or others macrolides.
* Patients retransplanted in the 14 days after the transplantation
* Patients with multivisceral failure
* Patients who have an introduction of tacrolimus 3 days after transplantation
* Patients who need complementary immunosuppressive drugs with corticoids excepted methylprednisolone used for reject
* Patients who received Prograf® per os or iv.
* Patients who received Cellcept® or Myfortic®
* Opposition to sign the formulary of consent or the understand the note of information

Primary outcomes:
measure: Blood concentration of tacrolimus (ng/mL)
timeFrame: Between day2 and day4 and day 10 and day14, after day 21
Secondary outcomes:
measure: "P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient.
timeFrame: Up to 3 years
measure: Factor V and prothrombin time
timeFrame: Up to 3 years
measure: Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology
timeFrame: Up to 3 years
measure: Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: AP-HP, Bicêtre Hospital
Study officials:
affiliation: AP-HP, Bicêtre Hospital
name: Emmanuel GONZALES, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: