Study to Compare Virological Response to 0.5 mg Daily Versus 1.0 mg Daily Oral Doses of Entecavir in Chronic Hepatitis B Virus Infection Related Decompensated Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Percent reduction in quantitative HBV DNA levels at 2 weeks post-treatment
研究概览
简要总结
Entecavir (ETV) and tenofovir (TDF) are the first-line drugs for treatment of chronic hepatitis B virus (HBV) infection. Chronic HBV infection gradually progress to liver cirrhosis. Over time, as liver damage and cirrhosis advance, the illness progress to a stage termed as decompensated cirrhosis, characterized by development of one or more of serious, life-threatening complications (ascites, hepatic encephalopathy, variceal bleeding or jaundice). In HBV related decompensated cirrhosis, antiviral treatment is shown to provide benefit.
For HBV related decompensated cirrhosis, EVT is the drug of choice as it has been shown to be effective and safe. The usual dose of ETV for chronic HBV infection is 0.5 mg orally once daily. Somehow, the recommended dose of ETV for decompensated cirrhosis has been 1.0 mg/d. The literature provides no justification for using this double dose of ETV. Since 0.5 mg daily works well in other stages of disease, there is little reason why it should not work well even in treatment-naïve decompensated cirrhosis. Considering the limitations of available literature, physicians' are divided in their opinion about the drug dose and are prescribing either of the two doses of ETV for this group. Hence, there is a need to assess whether the usual 0.5 mg/d of ETV would work as well as the 1.0 mg/d dose of ETV in decompensated cirrhosis due to HBV infection.
Investigators planned this open-labeled observational study with objective to compare the efficacy of HBV suppression achieved using 0.5 mg daily and 1.0 mg daily of ETV in HBV-related decompensated cirrhosis by comparing the mean reduction in HBV DNA level from baseline after 24 weeks of treatment.
In present study investigators propose to enroll 15 participants in each group who has been started on either doses (0.5 mg and 1.0 mg) of entecavir and measure serum HBV DNA levels in blood specimens (5 ml) will be collected at different time points, i.e. at baseline, 2, 4, 8, 12 and 24 weeks after starting entecavir.
详细描述
Background Chronic infection with hepatitis B virus (HBV), if untreated, may progress to liver cirrhosis, portal hypertension and hepatocellular carcinoma. Currently, oral administration of one of the nucleos(t)ide analogues (NAs) is the preferred treatment for chronic HBV infection. Of the five NAs approved for HBV treatment, lamivudine, adefovir and telbivudine are no longer preferred, and the recent guidelines from all three major international liver disease associations [American Association for the Study of Liver Disease (AASLD), European Association for Study of Liver (EASL), and Asia-Pacific Association for Study of Liver (APASL)] recommend the use of either entecavir (ETV) or tenofovir (TDF) as first-line drugs, because of their lower propensity to induce drug-resistant mutants and hence better efficacy.
Chronic liver disease due to any cause gradually progress to liver cirrhosis. Over time, liver damage and cirrhosis advances to a stage termed as decompensated cirrhosis, characterized by development of one or more of serious, life-threatening complications (ascites, hepatic encephalopathy, variceal bleeding or jaundice). Treatment of HBV infection with anti-viral drugs, in presence of decompensated cirrhosis, is beneficial.
In presence of HBV-related decompensated cirrhosis, EVT is the drug of choice as it has been shown to be effective and safe. The usual dose of ETV for chronic HBV infection is 0.5 mg orally once daily. Somehow, the recommended dose of ETV in presence of decompensated cirrhosis has been 1.0 mg/d. The literature provides little direct justification for using this double dose of ETV. Possibly, initially, ETV was used empirically in this dose to achieve a rapid HBV suppression in this high-risk group with prior exposure to lamivudine in advanced liver disease. However, since 0.5 mg daily works well in other stages of disease, there is little reason why it should not work well even in treatment-naïve decompensated cirrhosis. On the other hand, use of this higher dose of ETV adds to cost, a major consideration in areas where medical expenses are mostly met with out of the pocket expenses. Hene, in view of above-mentioned limitations of available literature, opinion of physicians is divided and either of the two doses of ETV is used in HBV related decompensated cirrhosis.
Hence, there is a need to assess whether the usual 0.5 mg/d of ETV would work as well as the 1.0 mg/d dose of ETV in decompensated cirrhosis due to HBV infection.
Hypothesis
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with decompensated liver cirrhosis and
- •Replicative HBV infection (HBsAg positive, serum HBV DNA titer >100,000 IU/mL) regardless of HBeAg and anti-HBe test results
排除标准
- •prior exposure to NAs or other specific treatment for HBV infection (e.g. pegylated interferon)
- •hepatocellular carcinoma
- •co-infection with any other hepatotropic viruses or HIV
- •acute-on-chronic liver failure as defined by Asia-Pacific Association for the Study of Liver criteria
- •significant alcohol intake or another concomitant hepatobiliary disease
- •expected survival below 4 weeks (e.g. hemodynamic instability, active sepsis, hepatorenal syndrome, etc)
- •use of immunosuppressive medication or
- •portal vein thrombosis.
研究组 & 干预措施
ETV 0.5 mg
Group of study participants who were started on 0.5 mg/day of entecavir
干预措施: Entecavir (Drug)
ETV 1.0 mg
Group of study participants who were started on 1.0 mg/day of entecavir
干预措施: Entecavir (Drug)
结局指标
主要结局
Percent reduction in quantitative HBV DNA levels at 2 weeks post-treatment
时间窗: 2 weeks from start of ETV treatment
Quantitative HBV DNA will be measured in study participants at 2 weeks post-treatment in participants receiving either intervention. Percent reduction at 2 weeks from baseline level will be compared between interventions.
Percent reduction in quantitative HBV DNA levels at 4 weeks post-treatment
时间窗: 4 weeks from start of ETV treatment
Quantitative HBV DNA will be measured in study participants at 2 weeks post-treatment in participants receiving either 0.5 mg or 1.0 mg daily doses of entecavir. HBV DNA will be measured after 2 weeks of ETV. Percent reductions at 4 weeks from baseline level will be compared.
次要结局
- Percent reduction in quantitative HBV DNA levels at 8, 12 and 24 weeks post-treatment(8, 12 and 24 weeks from start of ETV treatment)
- Change in disease severity as assessed by change in CTP score and change in MELD score(24 weeks from start of ETV treatment)