Assessment of the Pharmacokinetic Profile of Tacrolimus Medications and Their Relation to Effectiveness and Safety in Liver Transplant Patients

NCT05744635 | Recruiting FDA Drug

• 1 other identifier: LTA_2022
• Study Type: observational
• Target: 110
• Locations: 2 countries
• Sites: 2

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

Conditions

Liver Failure

Keywords

Liver transplantation; Immunosuppression; Tacrolimus

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic profile TL

  To compare the trough level (TL) of different tacrolimus containing medications to Envarsus at each visit

  12 months

• Pharmacokinetic profile TDD

  To compare the total daily dose (TDD) of different tacrolimus containing medications to Envarsus at each visit

  12 months

• Pharmacokinetic profile C/D

  To compare the ration of TL and TDD (C/D) of different tacrolimus containing medications to Envarsus at each visit

  12 months

Secondary Outcomes (11)

• Liver function GGT

  12 months

• Liver function AP

  12 months

• Liver function GOT

  12 months

• Liver function GPT

  12 months

• Renal function

  12 months

Study Arms (1)

Liver transplant patients, receiving tacrolimus containing immunosuppression

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. Possible medications are the following (dosages and administration according to local (European) SmPC * Envarsus prolonged release tablet * Adport hard capsule * Advagraf prolonged-release hard capsule * Modigraf granule for oral suspension * Prograf hard capsule * Tacforius hard capsule

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

Tacrolimus received as part of routine clinical care

Liver transplant patients, receiving tacrolimus containing immunosuppression

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult, liver (or concomittant liver-renal) transplant patients, receiving tacrolimus containing medications.

You may qualify if:

• Patients ≥ 18 years of age
• Patients after liver- or simultaneous liver and kidney transplantation
• Patients signed an informed consent form for use of their pseudonymised clinical data within the present non-interventional trial.

You may not qualify if:

• Hospitalisation due to infection, acute rejection, or graft disfunction 2 weeks prior to enrolment
• Chronic graft insufficiency in the patient's history
• 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)
• Presence of the following comorbidities:
• Diseases affecting adherence to therapy (Chronic neurologic conditions, Psychiatric diseases)
• Diseases affecting drug absorption and metabolism (Inflammatory bowel disease, Chronic inflammatory diseases of bile ducts, Presence of ascites due to any disease)
• Patients on waiting list for re-transplantation

Sponsors & Collaborators

• Chiesi Hungary Ltd.: lead
• Chiesi Slovenija, d.o.o.: collaborator

Study Sites (2)

Semmelweis University, Department of Surgery, Transplantation and Gastroenterology

Budapest, 1085, Hungary

RECRUITING

University Medical Center Ljubljana, Division of Internal Medicine, Department of Gastroenterology

Ljubljana, 1000, Slovenia

RECRUITING

MeSH Terms

Conditions

Liver Failure

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• László Piros, MD, PhD

  Semmelweis University, Department of Surgery, Transplantation and Gastroenterology, Budapest, Hungary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ákos Szeredi, MD

CONTACT

+36707772232; a.szeredi@chiesi.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 27, 2023
• Study Start: May 10, 2023
• Primary Completion: March 1, 2026
• Study Completion: June 1, 2026
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1); HU (1)