Phase II Trial of Long-term Monotherapy With Ribavirin Against Colchicine on Progression of Chronic Hepatitis C With Advanced Fibrosis in Patients With Non-response to Standard Antiviral Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- Hepatic disease progression defined by a difference of >2 mmHg in the hepatic venous gradient between the basal values and the end of treatment values in both groups
研究概览
简要总结
The rate of sustained virological response to a course of standard antiviral therapy (peg-interferon plus ribavirin) of patients with chronic hepatitis C infected by genotype 1 with advanced fibrosis (>F2) is rather low. Monotherapy with ribavirin reduces ALT levels and necroinflammatory liver activity in up to a half of non-responders to standard antiviral therapy, but without changes in liver fibrosis or viremia. Such a beneficial effect seems to be mainly due to the immunomodulatory effect of ribavirin. Portal pressure, as measured by HVPG, lowers in patients with chronic hepatitis C and advanced fibrosis with end-of-treatment response to peg-interferon plus ribavirin. Portal pressure reduction in this setting relates to a reduction of the necroinflammatory liver activity, but not with fibrosis amelioration. We hypothesize that monotherapy with ribavirin reduces portal pressure in hepatitis C patients with advanced fibrosis by means of its immunomodulatory and anti-inflammatory effects, and could constitute an alternative to non-responders to standard antiviral treatment. Portal pressure measurement has become a validated surrogate outcome measure in chronic liver disease, since decreasing portal pressure has shown consistent improvement in survival and clinical outcomes, such as complications of portal hypertension. The primary aim of this study is to investigate whether ribavirin monotherapy slows the progression of advanced chronic liver disease by hepatitis C as assessed by a reduction in HVPG.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HCV RNA in serum
- •AST/ALT greater than the upper limit of normal range
- •HVPG >5 mm Hg
- •Non-response or contraindication to a standard course of antiviral therapy
排除标准
- •Active alcoholism
- •HIV infection
- •Serum creatinine >1.2 mg/dl, hemoglobin <11 g/dl, hemolysis, symptomatic ischemic heart disease or cerebrovascular disease
- •Decompensated chronic liver disease
- •Pregnancy
- •Hypersensitivity to the drugs of the study
- •Severe concomitant disease
研究组 & 干预措施
Ribavirin
Ribavirin 1000-1200 mg qd
干预措施: Ribavirin (Drug)
Colchicine
Colchicine 0.5 mg bd
干预措施: Colchicine (Drug)
结局指标
主要结局
Hepatic disease progression defined by a difference of >2 mmHg in the hepatic venous gradient between the basal values and the end of treatment values in both groups
时间窗: 24 weeks
次要结局
- Decrease in the necroinflammatory activity and in the progression of fibrosis. Normalization of ALT levels.(24 weeks)
研究者
Agustin Albillos
Professor of Medicine
Hospital Universitario Ramon y Cajal