TACrolimus in Renal Transplantation: Individualization by Pharmacogenetic

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00552201
Recruitment Status : Completed
First Posted : November 1, 2007
Last Update Posted : May 27, 2010
Roche Pharma AG
Astellas Pharma Inc
Information provided by:
Centre Hospitalier Universitaire, Amiens

Brief 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.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Drug: Tacrolimus Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Therapeutic Study of a Treatment by Tacrolimus Adapted or Not According to the Genotype of the Cytochrome P450 3A5 After Renal Transplantation
Study Start Date : April 2006
Actual Primary Completion Date : January 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus
U.S. FDA Resources

Intervention Details:
    Drug: Tacrolimus
    Administration Twice a day after adjustment to blood level

Secondary Outcome Measures :
  1. Severity of the delayed restart of the renal function evaluated by the number [ Time Frame: 3 months ]
  2. of dialysis; [ Time Frame: 3 months ]
  3. C0 of Tacrolimus at D14, M1, M2 and M3; [ Time Frame: 3 months ]
  4. AUC (0-12h) of Tacrolimus at D14, M1 and M3; [ Time Frame: 3 months ]
  5. Time (in D) to obtain C0 targets of Tacrolimus between 10 and 15 ng/ml [ Time Frame: 3 months ]
  6. Number of dosage schedule adjustments for Tacrolimus necessary to obtaining [ Time Frame: 3 months ]
  7. first C0 target between 10 and 15 ng/ml; [ Time Frame: 1 month ]
  8. Global frequency of the clinical acute rejections; [ Time Frame: 3 months ]
  9. Time and incidence of the first episode of acute rejection proven and not by biopsy [ Time Frame: 3 months ]
  10. Renal graft function at M1 and M3 evaluated by the calculated [ Time Frame: 3 months ]
  11. creatinin clearance; [ Time Frame: 3 months ]
  12. Survival of the patients at M3; [ Time Frame: 3 months ]
  13. Survival of the grafts at M3; [ Time Frame: 3 months ]
  14. Number of adverse events at M3; [ Time Frame: 3 months ]
  15. Pharmacoeconomic impact at M3 evaluated by the duration of the initial [ Time Frame: 3 months ]
  16. hospitalization, the need of care (dialysis, rejection acute, opportunist infection) the frequency and duration of the hospitalizations during the first 3 months [ Time Frame: 3 months ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients, male or female, 18 to 65 years old.
  • Patients receiving a first or a second isolated renal graft coming from a donor alive or deceased,
  • The patients in age to procreate must have a negative test of pregnancy before being included in this study and will have to agree to use effective contraceptive measurements throughout the study.

-Patients able to include/understand the aims and the risks of the study, -having been fully informed and having given their writing consent to take part in this study. Patients unable to write and/or read but having fully understood the oral information given by the investigator and having given their oral consent in the presence of an independent witness. -

Exclusion Criteria:

  • Patients who receive several grafts.
  • Patients requiring a treatment by azathioprin.
  • Pregnant woman or nursing mother
  • Patients receiving an incompatible graft ABO.
  • Patients receiving or requiring immunosuppressant drugs prohibited by the protocol.
  • Patients with a peak of historical antibody equal to or greater than 50% of the panel.
  • Patients suffering from serious gastro-intestinal disorders which interfere with their capacity to receive or to absorb an oral form and patients presenting severe diarrhoea.
  • Patients with symptomatic GI ulcer HIV or HTLV1 positive patients or their donors
  • Patients presenting or having presented in the 5 last years one or several malignant tumours, except baso or spinocellular cutaneous epithelioma successfully treated.
  • Patients with systemic infections requiring a treatment at the entry in the study.
  • Patients having a leukocyte numeration lower than 2,5.109/l or haemoglobin lower than 5g/dl.
  • Patients with drug-addiction whatever it is, or psychiatric disorder which, according to the point of view of the investigator, could invalidate the communication with investigator or interfere with the compliance of the patient.
  • Patients who take part simultaneously in another therapeutic test or who received a study treatment less than 30 days before the entry in this study.
  • Patients having already been included in this study.
  • Patients allergic or intolerant with corticoids, macrolides, Tacrolimus, mycophenolate mofetil or basiliximab

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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 identifier (NCT number): NCT00552201

CHU Angers
Angers, France
CHU Rouen - Hôpital de Bois-Guillaume
Bois Guillaume, France, 76230
CHU de la côté de Nacre
Caen, France, 14033
CHU Gabriel Montpied
Clermont Ferrand, France, 63003
CHU Limoges - Hôpital Dupuytren
Limoges, France, 87042
CHU Poitiers- hôpital Jean Bernard
Poitiers, France, 86021
CHU Reims - Hôpital Maison Blanche
Reims, France, 51092
CHU Rennes - Hôpital Pontchaillou
Rennes, France, 35033
CHU Strasbourg - Hospices Civils
Strasbourg, France, 67091
CHU Tours - Hôpital Bretonneau
Tours, France, 37044
Sponsors and Collaborators
Centre Hospitalier Universitaire, Amiens
Roche Pharma AG
Astellas Pharma Inc
Principal Investigator: Gabriel Choukroun, MD, PhD CHU Amiens
Principal Investigator: Eric Thervet, Md, PhD Hôpital Necker, Paris

Responsible Party: CHOUKROUN Gabriel - Principal Investigator, CHU Amiens Identifier: NCT00552201     History of Changes
Other Study ID Numbers: TACTIQUE
First Posted: November 1, 2007    Key Record Dates
Last Update Posted: May 27, 2010
Last Verified: August 2009

Keywords provided by Centre Hospitalier Universitaire, Amiens:
kidney transplantation
P450 3A5 cytochrome

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