Renoprotective Effects of Telbivudine in Chronic Hepatitis B

December 15, 2018 updated by: Professor Yuen Man Fung, The University of Hong Kong

The Effect of Telbivudine on Renal Function in Chronic Hepatitis B Patients With Mild to Moderate Renal Impairment

Renal impairment is common in patients with chronic hepatitis B infection. For those taking nucleotide analogues, renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects. In this prospective study, consecutive CHB patients on combined lamivudine (LAM)+ADV/TDF are switched to LdT+ADV/TDF at recruitment and are followed up for 24 months. Estimated glomerular filtration rate (eGFR) is calculated with the Modification of Diet in Renal Disease (MDRD) equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers are investigated in cultured renal tubular epithelial cell line HK-2.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background

Both CHB and chronic kidney disease are major health issue affecting millions of persons worldwide. Based on a large European multicenter database, the Virgil-database, it is estimated that 15% and 4% of the CHB patients in Europe had mild (GFR 50-80ml/min) and moderate (GFR <50ml/min) renal impairment respectively . These group of patients require special attention as the nucleos(t)ides agents (NA) used in the treatment of CHB are cleared by kidneys and may worsen the kidney function. Recently, a subgroup analysis of the GLOBE study and 4 small prospective studies provide circumstantial evidence on the use of telbivudine (LDT) that can improve renal function in CHB patients. However, there are no prospective, controlled trials to date to evaluate the relationship between LDT and renal function.

Research plan and methodology

This is a prospective study in CHB patients treated with NA and pre-existing mild to moderate renal impairment defined as estimated GFR (eGFR) 30-90ml/min.

Aims

To compare the renal function of patients before and after switching lamivudine to telbivudine.

To determine any adverse events from switching other NA to telbivudine To determine any biochemical and virological change from switching other NA to telbivudine by checking ALT, HBV DNA at baseline, and at weeks 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks To determine any change in 24 hour urinary protein and urinary glucose level To determine the in vitro effects of telbivudine on renal tubular cells

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Department of Medicine, the University of Hong Kong, Queen Mary Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 - 70 years
  2. Documented HBsAg positivity for at least 6 months. Patients can be either HBeAg positive AND HBV DNA < 9 log10 copies/mL or HBeAg negative AND HBV DNA < 7 log10 copies/mL
  3. On combination therapy (lamivudine and tenofovir or lamivudine and adefovir) for at least 1 year
  4. Documented serum creatinine at least in 2 separate occasions in the last 1 year before recruitment
  5. MDRD eGFR 30-89ml/min at baseline

Exclusion Criteria:

  1. Concomitant liver disease including chronic hepatitis C and/or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis
  2. Significant alcohol intake or drug abuse
  3. Pregnant subjects
  4. Patients with co-existing significant chronic kidney disease (e.g.post renal transplantation etc.)
  5. Allergic to any of the medications involved in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: lamivudine + nucleotide analogue
At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued
Drug: Telbivudine
CHB patients who are receiving adefovir or tenofovir disoproxil fumarate are recruited. At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued. The patients are followed-up for 24 months.
Other Names:
  • lamivudine is switched to telbivudine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal function change
Time Frame: 108 weeks
Describe the change in renal function after 108 weeks of telbivudine switch
108 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Virologic suppression
Time Frame: 108 weeks
Rate of virologic suppression
108 weeks
Adverse events
Time Frame: 108 weeks
Rate of adverse events
108 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2013

Primary Completion (Actual)

June 16, 2016

Study Completion (Actual)

May 31, 2018

Study Registration Dates

First Submitted

December 12, 2018

First Submitted That Met QC Criteria

December 15, 2018

First Posted (Actual)

December 19, 2018

Study Record Updates

Last Update Posted (Actual)

December 19, 2018

Last Update Submitted That Met QC Criteria

December 15, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HKUCTR - 1639

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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