Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients

Liver Transplantation, Child Clinical Trial

— TACTHEP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02337036
• Other study ID #: P120904
• Secondary ID: 2013-000948-26
• Status: Recruiting
• Phase: N/A
• Start date: December 2013
• Est. completion date: December 2020

Study information

• Verified date: August 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: VERSTUYFT Céline, PhD, PharmD
• Phone: +33 (0)1 45 21 35 88
• Email: celine.verstuyft[@]bct.aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Transplantation, Child

Intervention

Other:
• Pharmacokinetic
Taking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus
• Pharmacogenetic
Pharmacogenetic study

Drug:
• Tacrolimus
These Patients are treated with tacrolimus after the Liver Transplantation

Locations

Country	Name	City	State
France	AP-HP, Bicêtre Hospital	Le Kremlin-Bicêtre

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

France, 

Outcome

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