Pharmacokinetics of Immunosuppressive Drugs in Heart Transplant Patients (PIGREC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT00812786
First received: December 19, 2008
Last updated: August 23, 2013
Last verified: December 2008
  Purpose

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).


Condition Intervention Phase
Heart Transplant
Drug: cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs)
Phase 4

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:
  • Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters. [ Designated as safety issue: No ]
  • Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.

Enrollment: 42
Study Start Date: July 2007
Study Completion Date: May 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00812786

Locations
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, France
Sponsors and Collaborators
University Hospital, Limoges
Investigators
Principal Investigator: Pierre MARQUET, MD University Hospital, Limoges
  More Information

No publications provided

Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT00812786     History of Changes
Other Study ID Numbers: 2006-006832-23
Study First Received: December 19, 2008
Last Updated: August 23, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Limoges:
heart transplantation
immunosuppressive drugs
individual dose adjustment
harmacokinetics
modelling

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Everolimus
Sirolimus
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on August 27, 2014