Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients (TACTHEP)

August 31, 2020 updated by: Assistance Publique - Hôpitaux de Paris

Building a Population Pharmacokinetic Model of Tacrolimus in Paediatric Liver Transplant Patients

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: Pharmacokinetic and Pharmacogenetic
Liver Transplant Children treated with tacrolimus
Other: Pharmacokinetic
Taking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus
Other: Pharmacogenetic
Pharmacogenetic study
Drug: Tacrolimus
These Patients are treated with tacrolimus after the Liver Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood concentration of tacrolimus (ng/mL)
Time Frame: Between day2 and day4 and day 10 and day14, after day 21
Residual concentration, Cmin, Cmax, Cl/F and Area Under the Curve of tacrolimus (AUC)
Between day2 and day4 and day 10 and day14, after day 21

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
"P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient.
Time Frame: Up to 3 years
Up to 3 years
Factor V and prothrombin time
Time Frame: Up to 3 years
To estimate a delayed graft function
Up to 3 years
Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology
Time Frame: Up to 3 years
Up to 3 years
Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus)
Time Frame: Up to 3 years
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Investigators

  • Principal Investigator: Emmanuel GONZALES, PhD, MD, AP-HP, Bicêtre Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2013

Primary Completion (Anticipated)

December 1, 2020

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

December 5, 2014

First Submitted That Met QC Criteria

January 8, 2015

First Posted (Estimate)

January 13, 2015

Study Record Updates

Last Update Posted (Actual)

September 1, 2020

Last Update Submitted That Met QC Criteria

August 31, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P120904
  • 2013-000948-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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