The Effect of Telbivudine on Renal Function in Chronic Hepatitis B Patients With Mild to Moderate Renal Impairment
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Renal function change
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 - 70 years
- •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
- •On combination therapy (lamivudine and tenofovir or lamivudine and adefovir) for at least 1 year
- •Documented serum creatinine at least in 2 separate occasions in the last 1 year before recruitment
- •MDRD eGFR 30-89ml/min at baseline
排除标准
- •Concomitant liver disease including chronic hepatitis C and/or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis
- •Significant alcohol intake or drug abuse
- •Pregnant subjects
- •Patients with co-existing significant chronic kidney disease (e.g.post renal transplantation etc.)
- •Allergic to any of the medications involved in the study
研究组 & 干预措施
lamivudine + nucleotide analogue
At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued
干预措施: Telbivudine (Drug)
结局指标
主要结局
Renal function change
时间窗: 108 weeks
Describe the change in renal function after 108 weeks of telbivudine switch
次要结局
- Virologic suppression(108 weeks)
- Adverse events(108 weeks)
研究者
Professor Yuen Man Fung
Deputy Head of Department
The University of Hong Kong