A Prospective, Randomized, Open-label, Multicenter Study to Evaluate the Peginterferon, Comparing to Nucleos(t)Ide Analogues, in Reducing the Incidence of HCC in Chronic Hepatitis B Patients With Intermediate to High Liver Cancer Risks
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 267
- 试验地点
- 9
- 主要终点
- Change of HBsAg level compared to baseline
研究概览
简要总结
China's new cases and deaths of hepatocellular carcinoma (HCC) rank first in the world. hepatocellular carcinoma is the third most morbid, second-most mortal malignancy in China. Up to 80% of hepatocellular carcinoma patients caused by HBV infection. Antiviral therapy can significantly reduce the incidence and mortality of hepatocellular carcinoma in patients with chronic hepatitis B (CHB), hinder the progression of liver disease, and effectively control the disease. However, studies in recent years have found that long-term therapy with Nucleos(t)ide analogue (NAs) cannot completely eliminate the risk of liver cancer in patients with chronic hepatitis B. In addition, a number of retrospective studies at home and abroad have shown that compared with long-term oral NAs, peginterferon can significantly reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B. However, there is limit prospective studies.
This multicenter, randomized, open-label, controlled trial study is aim to evaluate the pegylated interferon alfa-2b injection in comparing to NAs in reducing the incidence of hepatocellular carcinoma, to provide evidences for new management and treatment strategy options for improving clinical outcomes for the chronic hepatitis B patients. About 267 chronic hepatitis patients with intermediate to high risk of liver cancer who are now receiving nucleoside therapy will be enrolled. Subjects will be randomized into the peginterferon combined NAs group and the NAs monotherapy group at a ratio of 2:1. Level of HBsAg, proportion of patients with HBsAg clearance and seroconversion, incidence of liver cirrhosis and hepatocellular carcinoma will be assessed.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 60 years and no gender limit (including 18 and 60 years).
- •HBsAg positive for more than 6 months.
- •Patients with intermediate to high liver cancer risks. Refers to if at least one of the following items is met.
- •Male patient aged above 40 years.
- •Patients with a history of cirrhosis and/or family history of liver cancer.
- •Patients with metabolic diseases, such as diabetes, fatty liver, etc.
- •Any liver cancer assessment model of chronic hepatitis B patients suggested that liver cancer was at intermediate to high risk.
- •Have received Nucleos(t)ide analogue treatment for more than 24 weeks, and currently receiving Nucleos(t)ide analogue, while HBV DNA is undetectable (HBV DNA below 300 IU/mL or 1000 copies/mL).
- •Urine and/or serum pregnancy test within 24 hours prior to the first dose must be negative for female patients of childbearing potential.
- •Understand and voluntarily sign informed consent form.
排除标准
- •Patients co-infected with active hepatitis A, hepatitis C, hepatitis D, hepatitis E or HIV.
- •Patients who have previously received interferon therapy.
- •Alpha-fetoprotein greater than 100 ng/mL at screening, or liver imaging suggestive of liver tumor.
- •Decompensated liver disease (Child-Pugh score ≥ 5).
- •Pregnant or lactating women or patients planning to become pregnant or cannot to take contraception during the study.
- •Neutrophil count < 1.5 x 109/L, platelet count < 90 x 109 cells/L, or Creatinine 1.5 times higher than the upper limit of normal.
- •Patients with severe psychiatric history, particularly depression.
- •History of immune-mediated disease or levels of autoimmune antibodies markedly elevated.
- •Patients with severe diseases in major organ, such as heart, lung, kidney, brain, blood, etc., and patients with malignancies.
- •Patients with poorly controlled diabetes, hypertension, and thyroid disease.
- •Patients with history of severe retinopathy or other evidence of retinopathy.
- •Patient who ever received organ transplantation, or planning to receive organ transplantation.
- •Patients who are allergic to interferon or any of its ingredients.
- •Other circumstances that the investigator deems inappropriate to participate in this study.
研究组 & 干预措施
Combined treatment group
Peginterferon alfa-2b Injection combined Nucleos (t) ide Analogue therapy
干预措施: Peginterferon alfa-2b Injection, Nucleos (t) ide Analogue (Drug)
Monotherapy group
Nucleos (t) ide Analogue monotherapy
干预措施: Nucleos(t)ide analogue (Drug)
结局指标
主要结局
Change of HBsAg level compared to baseline
时间窗: week 48 of treatment
次要结局
- Incidence of liver cirrhosis and hepatocellular carcinoma(At week 48 of treatment and 5 years of follow up)
- Proportion of patients with HBsAg seroconversion(At week 48 of treatment and 5 years of follow up)
- Proportion of patients with HBsAg clearance(At week 48 of treatment and 5 years of follow up)
- Proportion of patients with change of liver stiffness measurement (LSM)(At week 48 of treatment and 5 years of follow up)
研究者
Qing XIe
Director of Department of Infectious Disease, Rui Jin Hospital
Ruijin Hospital