Renoprotective Effects of Telbivudine in Chronic Hepatitis B

Phase 4

Completed

• Conditions: Hepatitis B, Chronic; Chronic Kidney Diseases
• Interventions: Drug: Telbivudine

• Registration Number: NCT03778567
• Lead Sponsor: The University of Hong Kong

Brief Summary

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

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 Timeline

• Study Start: 2013-08-01
• Primary Completion: 2016-06-16
• Study Completion: 2018-05-31
• Status Verified: 2018-12
• Study First Submitted: 2018-12-12
• Study First Submitted QC: 2018-12-15
• Last Update Submitted: 2018-12-15
• Study First Posted: 2018-12-19
• Last Update Posted: 2018-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
lamivudine + nucleotide analogue	Telbivudine	At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued

Primary Outcome Measures

Name	Time	Method
Renal function change	108 weeks	Describe the change in renal function after 108 weeks of telbivudine switch

Secondary Outcome Measures

Name	Time	Method
Virologic suppression	108 weeks	Rate of virologic suppression
Adverse events	108 weeks	Rate of adverse events

Trial Locations

Locations (1)

Department of Medicine, The University of Hong Kong, Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong