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Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients (TACTHEP)

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ClinicalTrials.gov Identifier: NCT02337036
Recruitment Status : Unknown
Verified October 2016 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was:  Recruiting
First Posted : January 13, 2015
Last Update Posted : October 27, 2016
Sponsor:
Collaborator:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
Liver Transplantation, Child Other: Pharmacokinetic Other: Pharmacogenetic Drug: Tacrolimus Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Building a Population Pharmacokinetic Model of Tacrolimus in Paediatric Liver Transplant Patients
Study Start Date : December 2013
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

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




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. "P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient. [ Time Frame: Up to 3 years ]
  2. Factor V and prothrombin time [ Time Frame: Up to 3 years ]
    To estimate a delayed graft function

  3. Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology [ Time Frame: Up to 3 years ]
  4. Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus) [ Time Frame: Up to 3 years ]


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Ages Eligible for Study:   6 Months to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337036


Contacts
Contact: VERSTUYFT Céline, PhD, PharmD +33 (0)1 45 21 35 88 celine.verstuyft@bct.aphp.fr
Contact: Emmanuel GONZALES, PhD, MD +33 (0)1 45 21 21 21 emmanuel.gonzales@bct.aphp.fr

Locations
France
AP-HP, Bicêtre Hospital Recruiting
Le Kremlin-Bicêtre, France, 94275
Contact: Emmanuel GONZALES, PhD, MD    +33 (0)1 45 21 21 21    emmanuel.gonzales@bct.aphp.fr   
Contact: Celine Verstuyft, PhD, PharmD    +33 (1) 45 21 35 88    celine.verstuyft@bct.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
Principal Investigator: Emmanuel GONZALES, PhD, MD AP-HP, Bicêtre Hospital

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02337036     History of Changes
Other Study ID Numbers: P120904
2013-000948-26 ( EudraCT Number )
First Posted: January 13, 2015    Key Record Dates
Last Update Posted: October 27, 2016
Last Verified: October 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Liver transplantation
Child
Tacrolimus
Pharmacokinetic

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action