An Open, Multi-center Clinical Study of Combination Therapy With Tenofovir Disoproxil Fumarate and Peginterferon Alpha 2a in Nucleos(t)Ide Analogs Experienced Patients With HBV Related Hepatic Fibrosis.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Ratio of regression of fibrosis
研究概览
简要总结
Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.
详细描述
Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.
Main purpose: Comparing the improvement rate of liver fibrosis. Secondary purpose: Comparing the incidence of adverse events. Comparing the incidence of cirrhosis, hepatocellular carcinoma, and liver failure.
Comparing the rates of HBsAg and HBeAg serological conversion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year;
- •Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited;
- •Age from 18 to 55 years old;
- •Normal liver function(ALT<ULN,AST<ULN and TBil<ULN).
- •Undetectable hepatitis b virus DNA or less than 100IU/ml.
- •LSM between 6 and 12 kpa measured by fibroscan;
- •Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm.
排除标准
- •Decompensated cirrhosis, hepatocellular carcinoma or other malignancy;
- •Pregnancy, lactation or female has plan of pregnancy within 18 months;
- •Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)；
- •Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases;
- •Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions;
- •Patients who fail to comply with this research arrangement and sign an informed consent form
- •Patients can not follow-up;
- •Investigator considering inappropriate.
研究组 & 干预措施
TDF group
93 patients would receive treatment of oral medication of tenofovir disoproxil fumarate (TDF) 300mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
干预措施: Tenofovir Disoproxil Fumarate (Drug)
Combination group
93 patients would receive treatment of subcutaneous injection of peginterferon alfa 2a 180 μg once per week and meanwhile oral medication of tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
干预措施: Tenofovir Disoproxil Fumarate (Drug)
Combination group
93 patients would receive treatment of subcutaneous injection of peginterferon alfa 2a 180 μg once per week and meanwhile oral medication of tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
干预措施: PEG-Interferon alfa 2a (Drug)
结局指标
主要结局
Ratio of regression of fibrosis
时间窗: 48 weeks; 96 weeks
Regression of fibrosis was defined as liver stiffness measured by transient elastography changed from 9\~12kpa to 6\~9kpa or below, and from 6\~9kpa to less than 6kpa. After treatment, the proportion of patients with regression of fibrosis in the two groups was the ratio of regression of fibrosis, separately.
次要结局
- Ratio of loss of hepatitis b e antigen or/and seroconversion(24 week, 48 week, 72 week, 96 week)
- Ratio of loss of hepatitis b s antigen or/and seroconversion(24 week, 48 week, 72 week, 96 week)
- Logarithmic mean of HBsAg decline(24 week, 48 week, 72 week, 96 week)
研究者
Liang Peng
Professor
Third Affiliated Hospital, Sun Yat-Sen University