Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients

NCT ID: NCT02337036

Last Updated: 2020-09-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2020-12-31

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.

Conditions

Liver Transplantation, Child

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Pharmacokinetic and Pharmacogenetic

Liver Transplant Children treated with tacrolimus

Group Type: EXPERIMENTAL

Pharmacokinetic

Intervention Type: OTHER

Taking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus

Pharmacogenetic

Intervention Type: OTHER

Pharmacogenetic study

Tacrolimus

Intervention Type: DRUG

These Patients are treated with tacrolimus after the Liver Transplantation

Interventions

Pharmacokinetic

Taking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus

Intervention Type: OTHER

Pharmacogenetic

Pharmacogenetic study

Intervention Type: OTHER

Tacrolimus

These Patients are treated with tacrolimus after the Liver Transplantation

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel GONZALES, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

AP-HP, Bicêtre Hospital

Locations

AP-HP, Bicêtre Hospital

Le Kremlin-Bicêtre, , France

Site Status: RECRUITING

Countries

France

Central Contacts

VERSTUYFT Céline, PhD, PharmD

Role: CONTACT

celine.verstuyft@bct.aphp.fr

+33 (0)1 45 21 35 88

Emmanuel GONZALES, PhD, MD

Role: CONTACT

emmanuel.gonzales@bct.aphp.fr

+33 (0)1 45 21 21 21

Facility Contacts

Emmanuel GONZALES, PhD, MD

Role: primary

emmanuel.gonzales@bct.aphp.fr

+33 (0)1 45 21 21 21

Celine Verstuyft, PhD, PharmD

Role: backup

celine.verstuyft@bct.aphp.fr

+33 (1) 45 21 35 88

Other Identifiers

2013-000948-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P120904

Identifier Type: -

Identifier Source: org_study_id