Renoprotective Effects of Telbivudine in Chronic Hepatitis B

Chronic Kidney Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03778567
• Other study ID #: HKUCTR - 1639
• Status: Completed
• Phase: Phase 4
• Start date: August 1, 2013
• Est. completion date: May 31, 2018

Study information

• Verified date: December 2018
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: May 31, 2018
• Est. primary completion date: June 16, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.

Locations

Country	Name	City	State
Hong Kong	Department of Medicine, The University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal function change	Describe the change in renal function after 108 weeks of telbivudine switch	108 weeks
Secondary	Virologic suppression	Rate of virologic suppression	108 weeks
Secondary	Adverse events	Rate of adverse events	108 weeks