Pharmacokinetics of Immunosuppressive Drugs in Heart Transplant Patients (PIGREC)

University of Limoges (UL)

Status and phase

Completed

Phase 4

Conditions

Heart Transplant

Treatments

Drug: cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs)

Study type

Interventional

Funder types

Other

Identifiers

NCT00812786

2006-006832-23

Details and patient eligibility

About

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).

Full 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.

Enrollment

42 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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.