Liver Transplantation, ChildTACTHEPNCT02337036
Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients
A study testing Pharmacokinetic, Pharmacogenetic and Tacrolimus in people with Liver Transplantation, Child, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. This study is designed to assess the posology of tacrolimus in post-transplantation in the month after liver transplantation to obtain a… Read more about this study
- Who is it for?
- Ages 6 months to 12 years
- Conditions the study is for
- Liver Transplantation, Child
- What is being tested?
- Pharmacokinetic, Pharmacogenetic and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2013to Dec 2020
- Phase
- Interventional
- 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 6 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age of children who need to have a liver transplantation : between 6 month and 12 years
- Formulary of consent signed by the two parents.
- Children who need to receive tacrolimus per os (Modigraf® ) only after liver transplantation associated to Simulect® (basilixumab) in post-transplantation immediately as main
- Affiliation to the system of social protection.
Who cannot join
- Children who need a multi organs transplantation
- Hypersensibility or Contraindication to Modigraf® or others macrolides.
- Patients retransplanted in the 14 days after the transplantation
- Patients with multivisceral failure
- Patients who have an introduction of tacrolimus 3 days after transplantation
- Patients who need complementary immunosuppressive drugs with corticoids excepted methylprednisolone used for reject
Show all 9Show fewer
- Patients who received Prograf® per os or iv.
- Patients who received Cellcept® or Myfortic®
- Opposition to sign the formulary of consent or the understand the note of information
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
AP-HP, Bicêtre Hospital
Le Kremlin-Bicêtre, 94275
Emmanuel GONZALES, PhD, MD, +33 (0)1 45 21 21 21, emmanuel.gonzales@bct.aphp.fr
Celine Verstuyft, PhD, PharmD, +33 (1) 45 21 35 88, celine.verstuyft@bct.aphp.fr
About this study
Official title: Building a Population Pharmacokinetic Model of Tacrolimus in Paediatric Liver Transplant Patients
Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. This study is designed to assess the posology of tacrolimus in post-transplantation in the month after liver transplantation to obtain a therapeutic target between 10-15 ng/mL and the impact of biological and genetic factors on the pharmacokinetic parameters in paediatric liver transplant recipients.
Read the detailed description
Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. Therapeutic drug monitoring (TDM) of tacrolimus, based on whole-blood trough concentration (C0) values, is mandatory for use of twice-daily tacrolimus (Prograf_) as in order to decrease interindividual variability in exposure and thereby minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).
Until now, the C0 is the easiest means of individual dose adjustment, as only one blood sample is required and the clinician can easily calculate the dose needed to reach the target. Many factors have an impact on the pharmacokinetic parameters. However the adaptation of the time to achieve the target stays an issue. Among factors of inter and intra variability of pharmacokinetic of tacrolimus, some of them are specific of the pediatric liver transplantation population.
Aims: To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.
- Conditions
- Liver Transplantation, Child
- Being tested
- Pharmacokinetic, Pharmacogenetic, Tacrolimus
- Keywords
- Liver transplantation, Child, Tacrolimus, Pharmacokinetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PharmacokineticOther
Taking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus
PharmacogeneticOther
Pharmacogenetic study
TacrolimusDrug
These Patients are treated with tacrolimus after the Liver Transplantation
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Pharmacokinetic and Pharmacogenetic | Experimental | Liver Transplant Children treated with tacrolimus Receives: Other: Pharmacokinetic; Other: Pharmacogenetic; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood concentration of tacrolimus (ng/mL)
Residual concentration, Cmin, Cmax, Cl/F and Area Under the Curve of tacrolimus (AUC)
Measured: Between day2 and day4 and day 10 and day14, after day 21
Secondary outcomes (4)
"P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient.
Measured: Up to 3 years
Factor V and prothrombin time
To estimate a delayed graft function
Measured: Up to 3 years
Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology
Measured: Up to 3 years
Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus)
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2015 (estimated)
- Study startDec 2013
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Transplantation, ChildStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuel GONZALES, PhD, MD, Principal investigator, AP-HP, Bicêtre Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02337036
- Sponsor's protocol ID
- P120904
- Other IDs
- 2013-000948-26
- Acronym
- TACTHEP
- Status last verified
- Aug 2020
- First submitted
- 5 Dec 2014
- Last updated
- 1 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Building a Population Pharmacokinetic Model of Tacrolimus in Paediatric Liver Transplant Patients
- ClinicalTrials.gov ID
- NCT02337036
- Acronym / sponsor ID
- TACTHEP / P120904
- Conditions
- Liver Transplantation, Child
- Keywords
- Liver transplantation, Child, Tacrolimus, Pharmacokinetic
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Study start
- Dec 2013
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 13 Jan 2015 (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.
Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. This study is designed to assess the posology of tacrolimus in post-transplantation in the month after liver transplantation to obtain a therapeutic target between 10-15 ng/mL and the impact of biological and genetic factors on the pharmacokinetic parameters in paediatric liver transplant recipients.
Detailed description
Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. Therapeutic drug monitoring (TDM) of tacrolimus, based on whole-blood trough concentration (C0) values, is mandatory for use of twice-daily tacrolimus (Prograf_) as in order to decrease interindividual variability in exposure and thereby minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).
Until now, the C0 is the easiest means of individual dose adjustment, as only one blood sample is required and the clinician can easily calculate the dose needed to reach the target. Many factors have an impact on the pharmacokinetic parameters. However the adaptation of the time to achieve the target stays an issue. Among factors of inter and intra variability of pharmacokinetic of tacrolimus, some of them are specific of the pediatric liver transplantation population.
Aims: To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Pharmacokinetic and Pharmacogenetic | Experimental | Other: Pharmacokinetic, Other: Pharmacogenetic, Drug: TacrolimusLiver Transplant Children treated with tacrolimus |
Who may qualify
- Ages
- 6 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Age of children who need to have a liver transplantation : between 6 month and 12 years
- Formulary of consent signed by the two parents.
- Children who need to receive tacrolimus per os (Modigraf® ) only after liver transplantation associated to Simulect® (basilixumab) in post-transplantation immediately as main
- Affiliation to the system of social protection.
Key exclusion criteria (9 listed)
- Children who need a multi organs transplantation
- Hypersensibility or Contraindication to Modigraf® or others macrolides.
- Patients retransplanted in the 14 days after the transplantation
- Patients with multivisceral failure
- Patients who have an introduction of tacrolimus 3 days after transplantation
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 |
|---|---|---|
| PharmacokineticTaking blood samples for an Pharmacokinetic of tacrolimus in Paediatric Liver Transplant Patients treated with tacrolimus | Other | Arm 1: Pharmacokinetic and Pharmacogenetic |
| PharmacogeneticPharmacogenetic study | Other | Arm 1: Pharmacokinetic and Pharmacogenetic |
| TacrolimusThese Patients are treated with tacrolimus after the Liver Transplantation | Drug | Arm 1: Pharmacokinetic and Pharmacogenetic |
Primary outcome
Blood concentration of tacrolimus (ng/mL)
Time frame: Between day2 and day4 and day 10 and day14, after day 21
Residual concentration, Cmin, Cmax, Cl/F and Area Under the Curve of tacrolimus (AUC)
4 secondary outcomes
"P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient.
Time frame: Up to 3 years
Factor V and prothrombin time
Time frame: Up to 3 years
Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology
Time frame: Up to 3 years
Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus)
Time frame: Up to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2020.
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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.
Emmanuel GONZALES, PhD, MD principal investigator
AP-HP, Bicêtre Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pharmacokinetic, Pharmacogenetic and Tacrolimus in people with Liver Transplantation, Child, run by Assistance Publique - Hôpitaux de Paris at 1 site 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 4 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 1 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact VERSTUYFT Céline, PhD, PharmD (+33 (0)1 45 21 35 88, celine.verstuyft@bct.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood concentration of tacrolimus (ng/mL) (time frame: Between day2 and day4 and day 10 and day14, after day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Sep 2020.