Pharmacokinetics of Immunosuppressive Drugs in Heart Transplant Patients (PIGREC)

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: NCT00812786
Recruitment Status : Completed
First Posted : December 22, 2008
Last Update Posted : August 26, 2013
Information provided by (Responsible Party):
University Hospital, Limoges

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).

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

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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.
Study Start Date : July 2007
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.

Secondary Outcome Measures :
  1. Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters.
  2. Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

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): NCT00812786

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
Vandoeuvre Les Nancy, France
Sponsors and Collaborators
University Hospital, Limoges
Principal Investigator: Pierre MARQUET, MD University Hospital, Limoges

Responsible Party: University Hospital, Limoges Identifier: NCT00812786     History of Changes
Other Study ID Numbers: 2006-006832-23
First Posted: December 22, 2008    Key Record Dates
Last Update Posted: August 26, 2013
Last Verified: December 2008

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

Additional relevant MeSH terms:
Immunosuppressive Agents
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antitubercular
Antitubercular Agents