Phase 2 Randomized Multicenter Controlled Study of Ribavirin Pre-treatment (8 Weeks) Followed by Standard Therapy With Ribavirin and Pegylated Interferon (48 Weeks) in Transplanted Patients With Recurrence of Chronic Hepatitis C
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- HCV-RNA level, Transaminases level
研究概览
简要总结
The results of antiviral therapy in patients with recurrent hepatitis C after liver transplantation are lower than standard. Ribavirin has immune-modulating effects and seems to be crucial to optimize viral treatment. The aim of this multicenter controlled study is to examine the effect of Ribavirin pre-treatment preceding the combination therapy with peginterferon plus ribavirin on the sustained virological response.
详细描述
Ribavirin Pre-Treatment Study Protocol
- Introduction:
- Recurrence of hepatitis C infection and liver transplant:
Recurrence of hepatitis C after liver transplant is almost universal. After liver transplantation, the progression of chronic hepatitis C is more aggressive and an high percentage of recipients develop cirrhosis and rapid liver decompensation (1). Recent studies have shown that the long-term-survival-rate is significantly lower compared with non-HCV infected recipients (2). Other studies founded that antiviral treatment improves survival in these patients. Thus, the treatment of hepatitis C patients after LT is a priority for transplant units.
To date, the rate of sustained virologic response (SVR) in patients with recurrent hepatitis C after liver transplantation is about 20% with standard IFN and increases to 30% with pegylated IFN and Ribavirin (3). Lack in tolerability and low compliance to the antiviral therapy may represent an important limiting factor in order to improve the SVR. Severe myelosuppression is frequent in these patients, due to the additional effect of immunosuppressive therapy, being an additional reason to reduce antiviral drug dosage (3).
- Ribavirin:
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
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver transplantation from > 6 months
- •Positive HCV-RNA viremia
- •Elevated transaminase levels (greater than 1,2 normal values) in at least two consecutive determinations during the last month
- •Histology pattern showing hepatitis C recurrence
排除标准
- •Multiple organ transplantation
- •Histology showing evidence of hepatic allograft rejection > 3/9 RAI score
- •Concomitant active biliary disease
- •Concomitant HBV infection
- •Normal transaminases levels
- •Less than 1500 neutrophiles in more than one blood test
- •Less than 50000 platelets in more than one blood test
- •Hemoglobin < 9 g/ dL
- •Creatinine clearance < 35 ml/min
- •Positive antibodies > 1:80
- •Auto-immune thyroid pathology
- •Severe psychiatric disease
- •Diagnosis of ischemic cardiopathy in the last 12 months
- •Active alcohol abuse
- •Low compliance to other medical treatments
研究组 & 干预措施
ribavirin pre-treatment
patient will receive ribavirin in monotherapy for 8 weeks before the combined 48 weeks antiviral therapy
干预措施: ribavirin pre-treatment (Drug)
combined stardard therapy
patients will receive the standard combined therapy with ribavirin and pegylated interferon for 48 weeks
干预措施: ribavirin pre-treatment (Drug)
结局指标
主要结局
HCV-RNA level, Transaminases level
时间窗: 4°,12°,24°,36°48° week and six months after therapy conclusion
次要结局
- liver biopsy and Transient elastography at baseline and after six month since therapy conclusion(0°, 72° week)
研究者
Manuela Merli
professor
University of Roma La Sapienza