Heart TransplantPhase 4PIGRECNCT00812786
Pharmacokinetics of Immunosuppressive Drugs in Heart Transplant Patients
A Phase 4 study testing cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs) in people with Heart Transplant, run by University Hospital, Limoges at 12 sites in France.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Transplant
- What is being tested?
- cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs)
- How many people
- 42 participants
- Where
- 12 sitesFrance
- Study dates
- Jul 2007to May 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
France12 sites
CHU de Bordeaux
Bordeaux
CHU de Clermont-Ferrand
Clermont-Ferrand
CHU de Lille
Lille
CHU de Limoges
Limoges
Hôpital Louis Pradel - CHU de Lyon
Lyon
CHU de Nantes
Nantes
Hôpital Européen Georges Pompidou
Paris
Hôpital Pitié-Salpêtrière
Paris
CHU de Rennes
Rennes
CHU de Rouen
Rouen
CHU de Strasbourg
Strasbourg
CHU de NANCY
Vandœuvre-lès-Nancy
About this study
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.
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.
Read more
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).
Read the 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.
- Conditions
- Heart Transplant
- Being tested
- cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs)
- Keywords
- heart transplantation, immunosuppressive drugs, individual dose adjustment, harmacokinetics, modelling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2008 (estimated)
- Study startJul 2007
- Primary completionMay 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart TransplantStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre MARQUET, MD, Principal investigator, University Hospital, Limoges
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00812786
- Sponsor's protocol ID
- 2006-006832-23
- Acronym
- PIGREC
- Status last verified
- Dec 2008
- First submitted
- 19 Dec 2008
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26192348
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00812786
- Acronym / sponsor ID
- PIGREC / 2006-006832-23
- Conditions
- Heart Transplant
- Keywords
- heart transplantation, immunosuppressive drugs, individual dose adjustment, harmacokinetics, modelling
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- Jul 2007
- Primary completion
- May 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 22 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs) | Drug | – |
Primary outcome
Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.
2 secondary outcomes
Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters.
Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
- Results publication: PubMed 26192348Woillard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre MARQUET, MD principal investigator
University Hospital, Limoges
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs) in people with Heart Transplant, run by University Hospital, Limoges at 12 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00812786, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.