TACrolimus in Renal Transplantation: Individualization by Pharmacogenetic
Status:
Completed
Trial end date:
2008-12-01
Target enrollment:
Participant gender:
Summary
Renal transplantation is the treatment of choice of the chronic renal insufficiency arrived
at its final stage. Tacrolimus is an immunosuppressant treatment used for the prevention of
episodes of acute rejection. Tacrolimus is characterized by a narrow therapeutic index and
important interindividual variations of its pharmacokinetic characteristics. Proteins CYP3A4
and CYP3A5 are responsible of intestinal and hepatic metabolism of Tacrolimus. Various
polymorphisms for CYP3A5 and CYP3A4 were described and several retrospective studies
suggested an association between a genetic polymorphism of CYP3A5 and the pharmacokinetic
parameters of Tacrolimus. In particular, we showed that the presence of an allele CYP3A5*1
was associated to the use of more important amounts of Tacrolimus to obtain the desired blood
concentrations.
This study is a national, multicentric, prospective, opened, randomized on two arms of
treatment. 280 receivers of a renal transplant in 12 centres will be included. The genotyping
of gene CYP3A5 will be carried out in the 6 days following transplantation. During the first
week, the patients will be treated by basiliximab, MMF and corticosteroids. They will be
randomized (central randomization) in D6 to receive either Tacrolimus at 0.2 mg/kg/d, or at a
dosage adapted to their genotype. After determination of the first residual blood
concentration of Tacrolimus realized after six oral intakes, the daily amounts of Tacrolimus
could be modified if necessary to reach the desired blood concentrations. The total duration
of the study for a patient is 3 months after transplantation.
The objective of this study is to evaluate the impact of the adaptation, according to the
genotype of the CYP3A5 of the patient, of the first amount of Tacrolimus on the first
residual blood concentration of Tacrolimus, keeping in mind the aim of the individualization
of dosage schedule by pharmacogenetic approach.
Principal criterion : Comparison, between the two groups, of the percentage of patients for
whom the first blood concentration of Tacrolimus evaluated 3 days (D10) after the first
administration of Tacrolimus ranges between 10 and 15 ng/ml.
Statistics will be carried out in intention to treat. The principal criterion will be
analyzed by the test of chi-2.