Clinical trial NCT00812786: Pharmacokinetics of Immunosuppressive Drugs in Heart Transplant Patients
Official title: Multicentre, Open Study for the Setting up of Population Pharmacokinetic Models and Bayesian Estimators for Individual Dose Adjustment of Immunosuppressive Drugs (Cyclosporine, Tacrolimus, Mycophenolate Mofetil, Everolimus) During the First Year Post-grafting in Adult Heart Transplant Recipients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Transplant
Keywords: heart transplantation
immunosuppressive drugs
individual dose adjustment
harmacokinetics
modelling
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2008-12-22
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The main objective is to develop pharmacokinetic methods for individual dose adjustment of the global immunosuppressive treatment (cyclosporine, tacrolimus, mycophenolate mofetil and everolimus, taking into account the pharmacokinetic interactions), in order to optimise the efficiency and reduce the potentially severe sides effects of these drugs.

Forty five heart-transplant patients are to be included in this phase IV study to obtain a minimum of 10 patients treated with tacrolimus-mycophenolate, 10 with cyclosporine-mycophenolate and 20 with everolimus-cyclosporine.

Ten to 11 blood samples will be collected within the 8 to 12 hours post-dose in each patient and the immunosuppressive drug concentrations will be measured by LC-MS/MS.

The pharmacokinetic models and Bayesian estimators thus developed will provide tools for individual dose adjustment of immunosuppressive drugs simultaneously, at different post-transplant periods, using the area under the concentration-time curve (AUC) estimated using a limited number of time-points (2 or 3).

Detailed description: For each heart transplant patient, 10 to 11 blood samples (5 mL each) will be collected following dosing of he immunosuppressive drugs (at T0, T20', T40', T60', T90', T2h, T3h, T4h, T6h, T8h and T10h + T12h for inpatients), at several post-transplant periods (7 to 15 days, 1 month, 3 month and 1 year after transplantation). One more blood sample will be taken at D7-14 for pharmacogenetic analyses.

Eligibility criteria: Inclusion Criteria:

* Patient having received of a heart transplant (exclusively) less than 2 weeks before the inclusion date or planned to receive it within days following inclusion.
* Patient at least 18 years old, male or female.
* Patient treated with one of the following combination : cyclosporine-mycophenolate, tacrolimus-mycophenolate or everolimus- "low-dose" cyclosporine for at least 3 days, and at least 24 hours by the oral route at the time of the first sampling day (between 7 and 15 days post-transplant).
* Patient included or not in another study, in particular in a therapeutic trial (e.g. comparison between drug combinations).
* Patient having given written informed consent for his/her participation to the trial.

Exclusion Criteria:

* Patients in disagreement with the present trial.
* Patients suffering from neuro-psychic problems, making them unable to well-understand the protocol or to give a reliable consent.
* Patients with previous heart or any other solid organ transplantation.
* Patients with double transplantation (heart-lung, heart-kidney or heart-liver)
* Patients still intubated and ventilated 15 days post-transplant.
* Patients with anaemia between Day 7 and 15, as characterized by hematocrit \< 30% or haemoglobin \< 9 g/dl.

Primary outcomes:
measure: Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.
Secondary outcomes:
measure: Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters.
measure: Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Clermont-ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Lille
country: France
facility: CHU de Lille
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Hôpital Louis Pradel - CHU de Lyon
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Rennes
country: France
facility: CHU de Rennes
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Vandoeuvre Les Nancy
country: France
facility: CHU de NANCY
Study officials:
affiliation: University Hospital, Limoges
name: Pierre MARQUET, MD
role: PRINCIPAL_INVESTIGATOR
References: