Renoprotective Effects of Telbivudine in Chronic Hepatitis B
Condition: Hepatitis B, Chronic; Chronic Kidney Diseases
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 4

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
    

Intervention name(s): Telbivudine
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): lamivudine is switched to telbivudine
Intervention MeSH terms: Lamivudine; Telbivudine
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chronic hepatitis B infection; telbivudine; chronic kidney disease; nucleotide analogue