NCT00812786

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jul 2007

Longer than P75 for phase_4

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2007

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

December 19, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 22, 2008

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2011

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
Last Updated

July 30, 2025

Status Verified

December 1, 2008

Enrollment Period

3.8 years

First QC Date

December 19, 2008

Last Update Submit

July 28, 2025

Conditions

Keywords

heart transplantationimmunosuppressive drugsindividual dose adjustmentharmacokineticsmodelling

Outcome Measures

Primary Outcomes (1)

  • Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.

Secondary Outcomes (2)

  • Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters.

  • Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.

Interventions

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

CHU de Bordeaux

Bordeaux, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, France

Location

CHU de Lille

Lille, France

Location

CHU de Limoges

Limoges, France

Location

Hôpital Louis Pradel - CHU de Lyon

Lyon, France

Location

CHU de Nantes

Nantes, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Pitié-Salpêtrière

Paris, France

Location

CHU de Rennes

Rennes, France

Location

CHU de Rouen

Rouen, France

Location

CHU de Strasbourg

Strasbourg, France

Location

CHU de NANCY

Vandœuvre-lès-Nancy, France

Location

Related Publications (1)

  • Woillard JB, Saint-Marcoux F, Monchaud C, Youdarene R, Pouche L, Marquet P. Mycophenolic mofetil optimized pharmacokinetic modelling, and exposure-effect associations in adult heart transplant recipients. Pharmacol Res. 2015 Sep;99:308-15. doi: 10.1016/j.phrs.2015.07.012. Epub 2015 Jul 17.

MeSH Terms

Interventions

CyclosporineTacrolimusMycophenolic AcidEverolimus

Intervention Hierarchy (Ancestors)

CyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsMacrolidesLactonesOrganic ChemicalsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsSirolimus

Study Officials

  • Pierre MARQUET, MD

    University Hospital, Limoges

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 19, 2008

First Posted

December 22, 2008

Study Start

July 1, 2007

Primary Completion

May 1, 2011

Study Completion

May 1, 2012

Last Updated

July 30, 2025

Record last verified: 2008-12

Locations