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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-000948-26 | EudraCT Number |
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| Name | Class |
|---|---|
| Cliniques universitaires Saint-Luc- Université Catholique de Louvain | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Pharmacokinetic and Pharmacogenetic | Experimental | Liver Transplant Children treated with tacrolimus |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacokinetic | Other | Taking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| "P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient. | Up to 3 years | |
| Factor V and prothrombin time | To estimate a delayed graft function | Up to 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| VERSTUYFT Céline, PhD, PharmD | Contact | +33 (0)1 45 21 35 88 | celine.verstuyft@bct.aphp.fr | |
| Emmanuel GONZALES, PhD, MD | Contact | +33 (0)1 45 21 21 21 | emmanuel.gonzales@bct.aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Emmanuel GONZALES, PhD, MD | AP-HP, Bicêtre Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AP-HP, Bicêtre Hospital | Recruiting | Le Kremlin-Bicêtre | 94275 | France |
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| ID | Term |
|---|---|
| D000071184 | Pharmacogenomic Variants |
| D000071185 | Pharmacogenomic Testing |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D011110 | Polymorphism, Genetic |
| D014644 | Genetic Variation |
| D055614 | Genetic Phenomena |
| D005820 | Genetic Testing |
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| Pharmacogenetic | Other | Pharmacogenetic study |
|
| Tacrolimus | Drug | These Patients are treated with tacrolimus after the Liver Transplantation |
|
| Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology | Up to 3 years |
| Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus) | Up to 3 years |
| D019411 |
| Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |