Pharmacokinetics of Immunosuppressive Drugs in Heart Transplant Patients

Heart Transplant Clinical Trial

— PIGREC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00812786
• Other study ID #: 2006-006832-23
• Status: Completed
• Phase: Phase 4
• First received: December 19, 2008
• Last updated: August 23, 2013
• Start date: July 2007
• Est. completion date: May 2012

Study information

• Verified date: December 2008
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 2012
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Heart Transplant

Intervention

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

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	CHU de Clermont-Ferrand	Clermont-ferrand
France	CHU de Lille	Lille
France	CHU de Limoges	Limoges
France	Hôpital Louis Pradel - CHU de Lyon	Lyon
France	CHU de Nantes	Nantes
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Pitié-Salpêtrière	Paris
France	CHU de Rennes	Rennes
France	CHU de Rouen	Rouen
France	CHU de Strasbourg	Strasbourg
France	CHU de NANCY	Vandoeuvre Les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.			No
Secondary	Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters.			No
Secondary	Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.