Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up
研究概览
简要总结
The purpose of this study is to investigate whether in patients with chronic HBeAg-negative hepatitis B, PEG-IFN-ribavirin combination therapy for 1 year leads to enhanced response (HBV DNA <10E4 copies/ml and normal ALT 24 weeks after treatment discontinuation) in comparison with pegylated interferon (PEG-IFN) monotherapy.
详细描述
Despite the introduction of newer drugs for the treatment of chronic hepatitis B, there is still no optimal treatment. Pegylated interferon alfa has proven sustained efficacy in approximately 30-40% of patients with HBeAg-positive or HBeAg-negative chronic hepatitis B. It is likely that combination therapy of pegylated interferon alfa with ribavirin in chronic hepatitis B is more effective than pegylated interferon alfa monotherapy. In chronic hepatitis C, adding ribavirin to pegylated interferon therapy doubled the sustained response rate (29% vs. 56%) and has become the standard option of treatment.
To investigate the effect of the treatment with pegylated interferon and ribavirin on the amount of inflammation and fibrosis in the liver, a liver biopsy will be performed within one year prior to screening and at the end of follow-up.
When patients with chronic hepatitis B are treated outside any study with pegylated interferon, they visit the outpatient clinic approximately every month for blood samples. So in this study the amount of blood samples taken from every patient is not increased as compared with treatment outside a study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic hepatitis B
- •Biopsy performed within one year prior to screening or during screening
- •ALT > 1.5 x ULN
- •HBeAg negative, anti-HBeAg positive
- •HBV DNA > 10E5 copies/ml
- •Age 18-70 years
- •Written informed consent
- •Hepatic imaging without evidence of HCC
- •All fertile males and females must be using two forms of effective contraception
排除标准
- •Antiviral therapy against HBV within the previous 6 months; treatment with any investigational drug within 30 days of entry to this protocol
- •Severe hepatitis activity as documented by ALT > 10 x ULN
- •Advanced liver disease
- •Pre-existent leucopenia or thrombopenia
- •Co-infection with HCV,HDV or HIV
- •Other acquired or inherited causes of liver disease
- •Alpha fetoprotein > 50 ng/ml.
- •Evidence of severe renal disease
- •Hyper- or hypothyroidism
- •Significant cardiovascular or pulmonary dysfunction, malignancy,immunodeficiency syndromes
- •Immune suppressive treatment within the previous 6 months
- •Contra-indications for alpha-interferon therapy
- •Pregnancy, breast-feeding
- •Any medical condition requiring chronic systemic administration of steroids
- •Substance alcohol or drug abuse
- •Subjects with clinically significant retinal abnormalities
- •Subjects with clinically significant hearing abnormalities
- •Hemoglobinopathies
- •Subjects with known hypersensitivity to ribavirin
研究组 & 干预措施
1
Ribavirin + Peg IFN
干预措施: Ribavirin (Drug)
2
Peg IFN + Placebo
干预措施: Peginterferon alpha 2a (Drug)
结局指标
主要结局
The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up
时间窗: may 2008
次要结局
- HBV DNA negativity(undetectable by Taqman PCR)(May 2008)
- ALT normalization(May 2008)
- HBsAg loss from serum(May 2008)
- Improvement liver histology(May 2008)
- Combined virological, biochemical and histological response(May 2008)