Efficacy of Switch or Sequential Combination Therapy of Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients With Low HBsAg and HBeAg Titers After Long-term Entecavir Therapy: A Multicenter, Prospective Cohort Study
试验速览
- 阶段
- 不适用
- 入组人数
- 294
- 试验地点
- 17
- 主要终点
- Rate of HBeAg seroconversion
研究概览
简要总结
This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.
详细描述
Chronic hepatitis B (CHB) infection remains a global health treat. The ideal end point of therapy is HBsAg loss or HBsAg seroconversion, indicating a complete remission of CHB. In patients with HBeAg-positive CHB, sustained HBeAg seroconversion is also a desirable end point. Current therapies include pegylated interferon (PegIFN) finite and nucleos(t)ide analogues (NUCs) longterm therapy. However, only 30-40% of patients may achieve HBeAg seroconversion on PegIFN monotherapy, whereas 15-20% of patients on entecavir (ETV). Recently, accumulating evidence had shown that optimization of switching or combining PegIFN in patients on long-term ETV therapy may increase rate of HBeAg seroconversion and even lead to the complete eradication of HBV. However, these two regimens has not been tested adequately in patients with low HBsAg/HBeAg titers on long-term ETV therapy.
This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients > 18 and ≤ 60 years of age;
- •Positive HBsAg for more than 6 months;
- •Patients receiving previous ETV therapy ≥2 years;
- •Patients who have achieved undetectable HBV DNA, HBsAg <1500IU/mL and HBeAg <200S/CO prior to switch or S-C therapy;
- •ALT<=10*ULN and TB<2*ULN;
- •Patients who have been assigned to treatment with PegIFN (S-C or switch) or continuous ETV after previous ETV therapy
排除标准
- •Evidence of decompensated cirrhosis or hepatocellular carcinoma;
- •Serological evidence of co-infection with HCV, HDV or HIV;
- •Pregnant or breast-feeding women;
- •Patients with diseases that might contraindicate to PegIFN therapy including severe psychiatric diseases, immunological diseases, severe retinopathy, thyroid dysfunction, leukocytopenia, thrombopenia, etc
- •Patients receiving concomitant therapy with telbivudine;
- •A history of drug or alcohol abuse;
- •Other conditions that investigates consider not suitable for participate
研究组 & 干预措施
Switch group
Patients who have been assigned to pegylated interferon alfa-2a.
干预措施: Pegylated interferon alfa-2a (Drug)
Sequential combination group (S-C group)
Patients who have been assigned to pegylated interferon alfa-2a plus entecavir.
干预措施: Pegylated interferon alfa-2a plus Entecavir (Drug)
ETV group
Patients who have been assigned to entecavir monotherapy.
干预措施: Entecavir (Drug)
结局指标
主要结局
Rate of HBeAg seroconversion
时间窗: week 72 (24 weeks after 48 weeks of treatment)
Loss of HBeAg and detection of anti-HBe antibodies
次要结局
- Rate of HBV DNA <20IU/mL(week 72 (24 weeks after 48 weeks of treatment))
- Rate of HBsAg loss(week 72 (24 weeks after 48 weeks of treatment))
- Rate of HBsAg seroconversion(week 72 (24 weeks after 48 weeks of treatment))
- Percentage of patients reaching a ≥ 1log10 decline of quantitative HBsAg(week 72 (24 weeks after 48 weeks of treatment))
- Decline of quantitative HBsAg from baseline(week 72 (24 weeks after 48 weeks of treatment)
研究者
Wen-hong Zhang
Director of Division of Infectious Diseases
Huashan Hospital