Role of Rapid Virologic Response in Determining Treatment Duration of Peginterferon Alfa-2b/Ribavirin in Chronic Hepatitis C Genotype 4
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 280
- 试验地点
- 4
- 主要终点
- sustained virologic response defined as undetectable serum HCV RNA levels (Amplicor HCV, Roche Molecular Systems; lower limit of detection (LLD) of 50 IU/mL)
研究概览
简要总结
Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventional interferon monotherapy. Recent reports showed that pegylated interferon and ribavirin combination therapy markedly increased the SVR rate to 55-70%. The duration of treatment has not been accurately defined. The main objective of this is to assess the duration of pegylated interferon ribavirin therapy in chronic hepatitis genotype 4 and assess the clinical utility of rapid and early virologic response in determining the optimal duration of peg interferon ribavirin therapy in chronic hepatitis C.
详细描述
Hepatitis C virus (HCV) genotype 4 is the most frequent cause of chronic hepatitis C in Middle East, North Africa and sub-Saharan Africa. In countries like Egypt, 73 to 90% of cases of chronic hepatitis C are caused by genotype 4. Recently, epidemiological reports showed spread of HCV-4 infection in Western countries such as France, Italy, Greece, Spain and the United States particularly among intravenous drug users.
Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventional interferon monotherapy. Recent reports showed that pegylated interferon and ribavirin combination therapy markedly increased the SVR rate to 55-70%. We have previously shown that, treatment patients with chronic HVCG4with PEG-IFN α-2b plus ribavirin for 36 or 48 weeks was more effective (SVR 66% and 69%, respectively) than for 24 weeks.
It has been shown in previous studies on chronic hepatitis C genotype 1 that individuals who achieve an early virologic have a higher chance to achieve a sustained virologic response. Peg interferon and ribavirin therapy is associated with adverse events and is expensive; therefore, careful determination of the optimal treatment duration is crucial as it spares the patient unnecessary or prolonged therapy and enhances the cost-effectiveness of therapy.
Therefore the main objective of this randomized, multicenter trial is to assess the clinical utility of rapid and early virologic response in determining the optimal duration of peg interferon ribavirin therapy in chronic hepatitis C.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult males and females, 18 to 50 years of age; with documented chronic hepatitis C according to the following criteria: elevated serum alanine aminotransferase (ALT) above the upper limit of normal (40 U/l) on two occasions during the preceding six months; anti-HCV positive anti-body status assessed by second generation enzyme linked immunosorbent assay (Roche Diagnostics, Branchburg, New Jersey, USA); positive polymerase chain reaction for HCV RNA (Cobas Amplicor HCV Monitor v2.0; lower limit of quantitation 50 IU/mL); genotype 4; and criteria for chronic hepatitis C in liver biopsy performed within the preceding year with no signs of cirrhosis or bridging fibrosis on pretreatment liver biopsy.
排除标准
- •Previous IFN-alpha therapy; other liver diseases such as hepatitis A, hepatitis B, schistosomiasis, autoimmune hepatitis, alcoholic liver disease, drug induced hepatitis, or decompensated liver disease; coinfection with schistosomiasis or human immunodeficiency virus; neutro¬penia (,1 500/mm3); thrombocytopenia (,90 000/mm3); creatinine concentration .1.5 times the upper limit of normal; serum a fetoprotein concentration .25 ng/ml; organ transplant; neoplastic disease; severe cardiac or pulmonary disease; unstable thyroid dysfunction; psychiatric disorder; current pregnancy or breast feeding; or therapy with immunomodulatory agents within the last six months.
研究组 & 干预措施
1
- Pegylated IFN- alpha 2b
- Ribavirin for 24 weeks (patients with RVR)
干预措施: Pegylated IFN- alpha 2b (Drug)
1
- Pegylated IFN- alpha 2b
- Ribavirin for 24 weeks (patients with RVR)
干预措施: Ribavirin (Drug)
2
- Pegylated IFN- alpha 2b
- Ribavirin for 36 weeks (patients with complete EVR)
干预措施: Pegylated IFN- alpha 2b (Drug)
2
- Pegylated IFN- alpha 2b
- Ribavirin for 36 weeks (patients with complete EVR)
干预措施: Ribavirin (Drug)
3
- Pegylated IFN- alpha 2b
- Ribavirin for 48 weeks (patients with partial EVR)
干预措施: Pegylated IFN- alpha 2b (Drug)
3
- Pegylated IFN- alpha 2b
- Ribavirin for 48 weeks (patients with partial EVR)
干预措施: Ribavirin (Drug)
4
- Pegylated IFN- alpha 2b
- Ribavirin for 48 weeks (control)
干预措施: Pegylated IFN- alpha 2b (Drug)
4
- Pegylated IFN- alpha 2b
- Ribavirin for 48 weeks (control)
干预措施: Ribavirin (Drug)
结局指标
主要结局
sustained virologic response defined as undetectable serum HCV RNA levels (Amplicor HCV, Roche Molecular Systems; lower limit of detection (LLD) of 50 IU/mL)
时间窗: 18 months
次要结局
- Virologic response at the end of treatment (EOT) defined as undetectable HCV RNA serum levels (50 IU/ml) at the end of the scheduled treatment period(6-12 months and 6 months follow-up)
- sustained virologic response (primary) histological response (secondary) biochemical response (secondary)(6-12 months treatment), 6 months follow-up)