A Randomized, Open Labeled, Multicenter Study Comparing Entecavir Versus Lamivudine as Antiviral Prophylaxis for Patients With Hepatitis B Infection Undergoing Cytotoxic Chemotherapy for Malignant Tumors
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 5
- 主要终点
- The cumulative probability of HBV reactivation
研究概览
简要总结
Patients with chronic hepatitis B who are undergoing anticancer chemotherapy are at risk of HBV reactivation and hepatitis flare. Lamivudine (LAM) prophylaxis has been recommended in such circumstance according to the practice guidelines despite of limited evidence. However, failure of LAM prophylaxis including virologic breakthrough and withdrawal hepatitis occurs occasionally, which may lead to liver-related morbidity and mortality as well as premature interruption or a delay of chemotherapy. Given relatively frequent drug resistance of LAM, studies on the proper prophylactic antiviral regimen is warranted. The present multicenter, prospective, randomized study aims to compare the effect of entecavir (ETV) versus LAM for the prevention of HBV reactivation in HBsAg-positive patients with hematologic and oncologic malignancy undergoing cytotoxic chemotherapy.
详细描述
Chronic hepatitis B virus (HBV) carriers who are undergoing anticancer chemotherapy are at risk of HBV reactivation and hepatitis flare, and lamivudine (LAM) prophylaxis is recommended according to the practice guidelines despite of limited evidence. However, failure of LAM prophylaxis defined as virologic breakthrough during LAM therapy and withdrawal hepatitis after discontinuation of LAM therapy occurs occasionally, which may lead to liver-related morbidity and mortality as well as premature interruption or a delay of chemotherapy. Considering that LAM therapy showed relatively higher rates of drug resistance and of withdrawal hepatitis, studies on the better choice of prophylactic antiviral regimen is warranted.
The purpose of our study is to conduct a multicenter, prospective, randomized study comparing the effect of entecavir (ETV) versus LAM for the prevention of HBV reactivation in HBsAg-positive patients with hematologic and oncologic malignancy undergoing cytotoxic chemotherapy.
A total one hundred eighty HBV carriers with malignancy undergoing chemotherapy will be randomly assigned to each prophylactic therapy arm of ETV and LAM group. The primary endpoint of the study is the HBV reactivation rate during antiviral therapy and 6 months after discontinuation of prophylactic antiviral therapy.
If the prophylactic efficacy of ETV is superior to that of LAM, ETV will be the preferred prophylactic therapy for HBsAg-positive cancer patients undergoing chemotherapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older
- •positive for HBsAg for at least 6 months
- •inactive or active carrier of HBV with ALT level <2xULN, chronic hepatitis and compensated cirrhosis (Child-Pugh class A)
- •malignant tumors: non-Hodgkin's lymphoma undergoing systemic chemotherapy; solid tumors undergoing chemotherapy (including adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation therapy)
排除标准
- •positive for anti-HCV or anti-HIV antibodies
- •decompensated cirrhosis or hepatocellular carcinoma
- •expected survival of less than 1 year
研究组 & 干预措施
Lamivudine
LAM (100 mg/day) will be started within 1 week prior to initiation of the 1st cycle of chemotherapy, and continued until 24 weeks after completion of the last chemotherapy.
干预措施: Lamivudine (Drug)
Entecavir
ETV (0.5 mg/day) will be started within 1 week prior to initiation of the 1st cycle of chemotherapy, and continued until 24 weeks after completion of the last chemotherapy.
干预措施: Entecavir (Drug)
结局指标
主要结局
The cumulative probability of HBV reactivation
时间窗: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
10-fold or more elevation in serum HBV DNA titers above nadir
次要结局
- Incidence of HBV-related hepatitis flare(From the time of randomization until 24week after discontinuation of antiviral prophylaxis)
- Incidence of hepatic decompensation and liver-related mortality(From the time of randomization until 24week after discontinuation of antiviral prophylaxis)
- Cumulative probability of emergence of genotypic resistance(From the time of randomization until 24week after discontinuation of antiviral prophylaxis)
研究者
Sook-Hyang Jeong
Associate Professor
Seoul National University Bundang Hospital