Clinical trial NCT05744635: Assessment of the Pharmacokinetic Profile of Tacrolimus Medications and Their Relation to Effectiveness and Safety in Liver Transplant Patients
Official title: Assessment of the Pharmacokinetic Profile of Tacrolimus Medications in Liver Transplant Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Liver Failure
Keywords: Liver transplantation
Immunosuppression
Tacrolimus
Lead sponsor: Chiesi Hungary Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Chiesi Slovenija, d.o.o.
First posted: 2023-02-27
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult, liver (or concomittant liver-renal) transplant patients, receiving tacrolimus containing medications.

Brief summary: The goal of this observational study is oo compare the pharmacokinetic parameters of different tacrolimus containing medications in liver transplant patients. The main question\[s\] it aims to answer are:

* Differences in pharmacokinetic parameters of tacrolimus containing medicinal products (TL, TDD and their ratio - C/D)
* Changes in liver function parameters compared to baseline.
* Change in the estimated glomerular filtration rate (eGFR) compared to baseline.
* To assess the possible relation of liver function parameters and eGFR to C/D (blood concentration and daily dosage)
* Incidence of acute graft rejection during the study
* Incidence of BK and cytomegalovirus (CMV) infection during the study
* To assess the intraindividual variability of the TL, TDD and the ratios of these parameters (C/D)
* To assess the patient-adherence of therapy based on the BAASIS questionnaire, and prescription filled by individual patients, based on electronic health-care record.

Participants will not have to undergo any additional clinical visits or tests except which are required in routine clinical care

Detailed description: The primary aim of the study is to assess tolerability of LCPT and graft function within the 24-month observational period. Other objectives include the assessment of the intraindividual variability of the TL and TDD, the incidence of BK and cytomegalovirus infections, the incidence of graft insufficiency and acute and chronic graft rejection. There are few real-life studies available on maintenance treatment regimens in liver transplant patients throughout Europe, and these only focus on the healthcare resources' consumption. There is a lack of data describing the effectiveness of different drugs and their combinations in early maintenance immunosuppression in the real-life setting. Even less data is available of ISU (immunosuppression) drugs combinations' metabolism and its relation to effectiveness and safety, measured in liver transplant patients.

Given the above considerations we planned this non-interventional study (NIS) to assess pharmacokinetic parameters of LCPT and other tacrolimus containing medications and their relation to efficacy and tolerability in hepatic allograft recipients in a real-life setting.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥ 18 years of age
2. Patients after liver- or simultaneous liver and kidney transplantation
3. Having received a tacrolimus containing immunosuppressant therapeutic regimen at least for four weeks (induction therapy), and TL is within 5-20 ng/ml before inclusion
4. Patients signed an informed consent form for use of their pseudonymised clinical data within the present non-interventional trial.

Exclusion Criteria:

1. Participation in any clinical trial, 30 days prior to inclusion
2. The patients received liver allograft more than 6 months before inclusion
3. Hospitalisation due to infection, acute rejection, or graft disfunction 2 weeks prior to enrolment
4. Chronic graft insufficiency in the patient's history
5. Use of medications 2 weeks prior to enrolment, or the need for continuous use of medications that are known to significantly affect the pharmacokinetics of tacrolimus containing medications (as CYP3A4 inducers: rifampin, carbamazepine, phenobarbital, and phenytoin, or CYP3A4 inhibitors: erythromycin, ketoconazole, clarithromycin, and verapamil containing medication)
6. Presence of the following comorbidities:

   1. Diseases affecting adherence to therapy (Chronic neurologic conditions, Psychiatric diseases)
   2. Diseases affecting drug absorption and metabolism (Inflammatory bowel disease, Chronic inflammatory diseases of bile ducts, Presence of ascites due to any disease)
7. Patients on waiting list for re-transplantation

Primary outcomes:
measure: Pharmacokinetic profile TL
timeFrame: 12 months
measure: Pharmacokinetic profile TDD
timeFrame: 12 months
measure: Pharmacokinetic profile C/D
timeFrame: 12 months
Secondary outcomes:
measure: Liver function GGT
timeFrame: 12 months
measure: Liver function AP
timeFrame: 12 months
measure: Liver function GOT
timeFrame: 12 months
measure: Liver function GPT
timeFrame: 12 months
measure: Renal function
timeFrame: 12 months
measure: Kinetics and function
timeFrame: 12 months
measure: Rejection
timeFrame: 12 months
measure: Virus infection
timeFrame: 12 months
measure: Variability
timeFrame: 12 months
measure: Adherence BAASIS
timeFrame: 12 months
measure: Adherence prescriptions
timeFrame: 12 months
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Semmelweis University, Department of Surgery, Transplantation and Gastroenterology
city: Ljubljana
country: Slovenia
facility: University Medical Center Ljubljana, Division of Internal Medicine, Department of Gastroenterology
Study officials:
affiliation: Semmelweis University, Department of Surgery, Transplantation and Gastroenterology, Budapest, Hungary
name: László Piros, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: