A Randomized Controlled Trial on the Efficacy of Tenofovir Disoproxil Fumarate (TDF)-Switch Therapy in Chronic Hepatitis B Patients With Incomplete Response to Entecavir
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maintained virologic response
研究概览
简要总结
Currently, five nucleos(t)ide analogs are approved for the treatment of chronic hepatitis B, namely lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). ETV and TDF are recommended as first-line therapy by all regional guidelines due to their high anti-viral potency and low risk of inducing resistance.
ETV monotherapy for chronic HBV infection is highly effective in both HBeAg-positive and negative treatment-naïve patients. The cumulative probability of maintained virologic suppression with undetectable HBV DNA at year 1, 2 and 3 were 76.5%, 83.0% and 88.3% respectively.
TDF is another potent anti-viral treatment for chronic hepatitis B. Up to 72% and 87% of HBeAg-positive and -negative patients achieved undetectable HBV DNA by week 144 of TDF monotherapy. It is also effective in patients with prior exposure to other nucleo(s)tide analogs. Previous studies demonstrated that TDF can be used as an effective rescue therapy in lamivudine or adefovir-treated patients with incomplete virologic response.
However, the optimal treatment for patients with suboptimal response to ETV is uncertain. With this background, we will conduct a randomized controlled trial to evaluate the efficacy of TDF switch therapy in patients with incomplete virologic response to ETV treatment.
详细描述
Chronic hepatitis B virus (HBV) infection affects approximately 400 million people worldwide, and three-quarter of them are from Asia-Pacific region [1-3]. Nucleos(t)ide analogs treatment can suppress viral replication, delay cirrhotic complications and reduce the risk of hepatocellular carcinoma (HCC) [4-5].
Currently, five nucleos(t)ide analogs are approved for the treatment of chronic hepatitis B, namely lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). ETV and TDF are recommended as first-line therapy by all regional guidelines due to their high anti-viral potency and low risk of inducing resistance [6-8].
ETV monotherapy for chronic HBV infection is highly effective in both HBeAg-positive and negative treatment-naïve patients [9-10]. The cumulative probability of maintained virologic suppression with undetectable HBV DNA at year 1, 2 and 3 were 76.5%, 83.0% and 88.3% respectively [11].
TDF is another potent anti-viral treatment for chronic hepatitis B. Up to 72% and 87% of HBeAg-positive and -negative patients achieved undetectable HBV DNA by week 144 of TDF monotherapy [12]. It is also effective in patients with prior exposure to other nucleo(s)tide analogs. Previous studies demonstrated that TDF can be used as an effective rescue therapy in lamivudine or adefovir-treated patients with incomplete virologic response [13-14].
The importance of complete viral suppression should be emphasized. In treatment-naïve patients, there is a positive correlation between HBV DNA level with risk of developing cirrhosis and HCC [15-17]. In a recent report on 372 ETV-treated patients, suppression of HBV DNA to less than 2000 IU/ml was associated with lower risk of disease progression among those with cirrhosis at baseline [18]. Therefore, suppressing HBV DNA to undetectable level should be the treatment target, especially in patients with established cirrhosis who are at the greatest risk of HCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 or above
- •Positive hepatitis B surface antigen for at least 6 months
- •On ETV monotherapy as anti-viral treatment for at least 52 weeks
- •HBV DNA (>20 IU/ml) at week 52 or more of ETV treatment
- •Written informed consent obtained
排除标准
- •Concurrent use of other antiviral treatment (including oral nucleos(t)ide analogs, interferon or pegylated interferon) for chronic hepatitis B.
- •Concurrent use of steroids or immunosuppressive agents more than two week consecutively
- •Co-infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
- •Features suggestive of concomitant chronic liver diseases: positive anti-nuclear antibody (ANA) titer above 1/160, positive anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), abnormal serum ceruloplasmin or iron profile, or histological features of alternative chronic liver disease
- •Pregnancy or breast feeding.
- •Inability or unwillingness to give informed consent or abide by the requirements of the study.
- •History of other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
- •Patients with baseline significant impaired renal function with creatinine clearance <30 ml/min or receiving dialysis for end stage renal disease.
研究组 & 干预措施
Entecavir
Entecavir 0.5mg QD for 48 weeks
干预措施: Entecavir (Drug)
tenofovir disoproxil fumarate
tenofovir disoproxil fumarate 300mg QD for 48 weeks
干预措施: tenofovir disoproxil fumarate (Drug)
结局指标
主要结局
Maintained virologic response
时间窗: 48 weeks
Undetectable HBV DNA by PCR assay
次要结局
- Amino acid substitutions or drug resistance(At week 48)
- Normal ALT, RFT and bone profile(At week 24 and 48)
- Numbers of adverse events or serious adverse events(At week 48)
- Undetectable HBV DNA at week 24 and 48(At week 24 and 48)
研究者
Prof Wong, Lai Hung Grace
Associate Professor
Chinese University of Hong Kong