Clinical Outcome of Liver Transplant Patients With Tacrolimus-based Immunosuppression

The Influence of Genetic and Clinical Factors on Clinical Outcome of Liver Transplant Patients With Tacrolimus-based Immunosuppression

Genetic polymorphism and numerous clinical factors could influence tacrolimus pharmacokinetics, which led to large inter-and intra-individual variability.Since its narrow therapeutic range,predicting therapeutic outcome and individualized dosage remains to be a challenge. The study's objective is to identify the genetic and clinical factors that can influence clinical outcome in liver transplant.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation

Detailed Description

A great number of studies had found significant correlation between tacrolimus pharmacokinetics and gene polymorphism. However, previous studies on the correlation between genetic factors and clinical outcome were controversial. Furthermore, most studies focused on single genetic polymorphism and clinical outcome, and very limited studies took multiple genetic factors and clinical factors into account.

This is a retrospective study. Eligible patients were those who had signed informed consent for genetic study in previous research projects ( IRB approval number：201512005RINC and 201612023RIND ). The present study will collect laboratory data, concurrent medications, and therapeutic drug monitoring (TDM) data. Patient survival, graft survival, acute rejection and tacrolimus-associated adverse events will be assessed.

• Study Type: Observational
• Enrollment (Actual): 113

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who underwent living donor liver transplantation (LDLT) during 2008 to 2017 in National Taiwan University Hospital and received tacrolimus-based immunosuppression.

Description

Eligible patients were those who had signed informed consent for genetic study in our previous research projects.

Inclusion Criteria of the Previous Study:

• patients who underwent living-donor liver transplantation during January 2008 to December 2017
• at the age of 20-65
• with tacrolimus-based immunosuppression after liver transplant for at least 6 months.

Exclusion Criteria of the Previous Study :

• retransplantation
• multi-organ transplantation
• human immunodeficiency virus (HIV) positive.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of patients with biopsy proven acute rejection (BPAR)	Incidence of BPAR will be estimated with Kaplan-Meier analysis	up to 12 months after liver transplantation
Graft survival	incidence of graft loss will be estimated Kaplan-Meier analysis	up to 9 years after liver transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with tacrolimus-associated adverse events	Common adverse events of tacrolimus such as nephrotoxicity, post-transplant diabetes mellitus, hypertension, infection, hyperlipidemia and malignancy.; nephrotoxicity：decreased renal function estimated by glomerular filtration rate(GFR) using MDRD 4-Variable Equation; Post-transplant diabetes mellitus：defined by diagnosis and the use of antihyperglycemic agents, laboratory data including blood sugar(mg/dL) and hemoglobin A1c (percentage); hypertension：defined by diagnosis and the use of antihypertensive agents, laboratory data including blood pressure(mmHg); infection：defined by diagnosis of infection and the use of antiinfective agents; Hyperlipidemia：defined by diagnosis and the use of lipid-lowering agents, laboratory data including LDL (mg/dL), HDL (mg/dL) and total cholesterol (mg/dL); malignancy：incidence of cancer	up to 9 years after liver transplantation
Patient survival	incidence of death	up to 9 years after liver transplantation

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Rey-Heng Hu, Professor, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): October 8, 2019
• Study Completion (Actual): September 22, 2020

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (Actual): January 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 14, 2021
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: immunosuppressant; tacrolimus; liver transplant; gene polymorphism
• Other Study ID Numbers: 201812015RINC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No