Replacement of Lamivudine by Telbivudine to Improve Renal Function

Replacement of Lamivudine by Telbivudine to Improve Renal Function for Post-transplant Hepatitis B Patients - a Randomized Clinical Trial

Nephrotoxicity is one of the adverse effects of lamivudine and dosage of lamivudine has to be reduced if patients' renal function is insufficiency. Telbivudine may improve glomerular filtration rate. This study is to see whether renal function is improved when Lamivudine is replaced by telbivudine in liver transplantation patients.

Study Overview

• Status: Completed
• Conditions: Virus Diseases; Disorder Related to Transplantation; Injury Due to Exposure to External Cause
• Intervention / Treatment: Drug: telbivudine

Detailed Description

Liver transplantation is the only effective treatment for the patients with liver failure. Hepatitis B-related liver cirrhosis is the major indication to have liver transplantation in Taiwan. After liver transplantation, prophylaxis of hepatitis B recurrence will be performed by anti-hepatitis B immunoglobulin and anti-viral agents. Currently, lamivudine is the drug the investigators choose to prevent HBV recurrence for many years because it is safe for long-term use. However, nephrotoxicity is one of the adverse effects of lamivudine and dosage of lamivudine has to be reduced if patients' renal function is insufficiency. Recently, the studies on chronic hepatitis B patients showed improvement of glomerular filtration rate for those receiving telbivudine treatment. In this study, the investigators will include our post-transplant HBV patients who have stable liver function, receive lamivudine for prophylaxis of recurrent hepatitis B, and have renal dysfunction in stage II-IV. The patients will be randomized to receive telbivudine or lamivudine continuously at 1:1 ratio. Renal function will be examined at 6 months interval to determine whether renal function is improved. The achievement will determine whether telbivudine is better than lamivudine for the HBV patients with renal dysfunction.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign inform consent
2. Age is not less than 16 years old.
3. Post liver transplantation patient for HBV-related indication.
4. Chronic hepatitis B transplant patients who are treated by lamivudine for not less than 6 months.
5. eGRF stage 2-4 patients (15<eGFR<90ml)
6. Stable liver function, ALT not more than 2 folds of upper limit.

Exclusion Criteria:

1. Acute rejection with increase CNI dose within a month.
2. Pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Lamivudine group; continue Lamivudine
Experimental: Telbivudine group; Telbivudine replaces Lamivudine	Drug: telbivudine; telbivudine replace Lamivudine; Other Names: sobivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function measurement	Measure eGFR when the patients were enrolled, every 2 months and up to 12 months. The most important time point will be to compare eGRF at 6 month and 12 months after medication conversion to the beginning levels. Renal function is improved if eGRF is better after medication conversion.	every 2 months, up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hepatitis B recurrence	Measure hepatitis B surface antigen every 6 months. If HBs AG appears, hepatitis B recurrence is diagnosed.	every 6 months, up to 12 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Lee WC, Wu TH, Wang YC, Cheng CH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee CS. Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease. Biomed Res Int. 2017;2017:9324310. doi: 10.1155/2017/9324310. Epub 2017 Aug 13.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: June 3, 2013
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: February 5, 2017
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Telbivudine
• Other Study ID Numbers: CGMH-IRB-101-3476A3