Renoprotective Effects of Telbivudine in Chronic Hepatitis B

NCT ID: NCT03778567

Last Updated: 2018-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-01

Study Completion Date

2018-05-31

Brief Summary

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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.

Detailed Description

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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

Conditions

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Hepatitis B, Chronic Chronic Kidney Diseases

Keywords

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chronic hepatitis B infection telbivudine chronic kidney disease nucleotide analogue

Study Design

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Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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lamivudine + nucleotide analogue

At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued

Group Type OTHER

Telbivudine

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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lamivudine is switched to telbivudine

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Professor Yuen Man Fung

Deputy Head of Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Man-Fung Yuen, DSc, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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Department of Medicine, The University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Countries

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Hong Kong

References

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Mak LY, Liu SH, Yap DY, Seto WK, Wong DK, Fung J, Chan TM, Lai CL, Yuen MF. In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue. Dig Dis Sci. 2019 Dec;64(12):3630-3641. doi: 10.1007/s10620-019-05717-0. Epub 2019 Jul 6.

Reference Type DERIVED
PMID: 31280390 (View on PubMed)

Other Identifiers

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HKUCTR - 1639

Identifier Type: -

Identifier Source: org_study_id