Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- the rates of HBeAg seroconversion
研究概览
简要总结
Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.
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
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≥16 years
- •HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
- •Serum HBVDNA >2×10^4IU/ml
- •80U/L < serum ALT < 400U/L, and TBIL < 34 umol/L
- •Serum ALT < 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3
排除标准
- •Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
- •Hepatic decompensation
- •received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
- •Blood routine examination: WBC <3×10^9/L，neutrophile granulocyte < 1.5×10^9/L，PLT <80×10^9/L
- •Renal function: creatinine >1.5 times of upper normal limit
- •Alcoholism or a history of addiction and abuse
- •Combined with hepatocarcinoma
研究组 & 干预措施
Peg-IFNα-2a monotherapy
Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.
干预措施: Peg-IFNα-2a (Drug)
Sequential therapy
Participants will receive entecavir monotherapy for 12 weeks, and 180ug peg-IFNα-2a therapy is added for the following 12 weeks. After that, entecavir will be stopped and 180ug peg-IFNα-2a monotherapy for the following 48 weeks. All participants will followed to 96 weeks.
干预措施: Peg-IFNα-2a (Drug)
Sequential therapy
Participants will receive entecavir monotherapy for 12 weeks, and 180ug peg-IFNα-2a therapy is added for the following 12 weeks. After that, entecavir will be stopped and 180ug peg-IFNα-2a monotherapy for the following 48 weeks. All participants will followed to 96 weeks.
干预措施: Entecavir (Drug)
Combination therapy
Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
干预措施: Peg-IFNα-2a (Drug)
Combination therapy
Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
干预措施: Entecavir (Drug)
结局指标
主要结局
the rates of HBeAg seroconversion
时间窗: at week 72
次要结局
- normalisation of ALT(at week 2、4、12、24、36、48、60、72、84、96)
- liver histological improvement(at baseline and at week 72)
- The rates of HBsAg negative(at week12、24、36、48、60、72、84、96)
- the rate of virological response(at week 4、12、24、36、48、60、72、84、96)
- the rate of HBeAg negative(at week 12、24、36、48、60、72、84、96)