Anticoagulation for Liver Fibrosis in Patients With Hepatitis C Virus Infection: Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Median Liver Stiffness Value
研究概览
简要总结
Patients who have been treated for hepatitis C virus (HCV) infection who have failed to respond to anti-viral treatment are often concerned about their ongoing liver disease and are therefore looking for alternative treatments which might prevent fibrosis progression. This view is endorsed by patient representative groups (including Charles Gore at the HepC Trust) who have welcomed this trial protocol.
The study is a single centred, prospective, open labelled design. Practical as well as safety concerns dictated that the study could not be conducted in a blinded fashion, since patients taking anticoagulation require monitoring. The study consisted of two 8 week phases: Phase 1 and Phase 2. Phase 1 (observation phase, 0 to 8 weeks) and Phase 2 (treatment phase with warfarin anticoagulation, 8 to 16 weeks). Study completed at end of Phase 2.
详细描述
Background:
Convincing evidence exists outlining a role for the coagulation system in the pathogenesis of liver fibrosis. In vivo and in vitro studies have suggested a role for thrombin and FXa in activating hepatic stellate cells and epidemiological studies have demonstrated that prothrombotic states accelerate liver fibrosis (Wright et al., 2003).
Hence if prothrombotic states accelerate liver fibrosis, conversely anticoagulation should slow liver fibrosis. Animal studies have confirmed this (Anstee et al., 2008; Duplantier et al., 2004), and confirmed the beneficial effect of inhibiting the coagulation cascade. The number of patients with HCV infection on anticoagulants is small and there is no published case series. Similarly there are problems assessing disease progression using patients with haemophilia and HCV infection. The therapeutic use of anticoagulation to prevent fibrosis in humans is not without precedent, and warfarin has demonstrated a survival benefit in pulmonary fibrosis (Kubo et al., 2005).
The antifibrotic potential of warfarin anticoagulation needs to be formally assessed in the setting of a clinical trial using patients with documented liver fibrosis. Most previous human studies of antifibrotics have taken place in patients with chronic HCV infection who have failed anti-viral therapy, as they are a model of progressive fibrosis (Anstee et al., 2009).
Study aims:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 17 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged >17 years (male and female)
- •HCV infection PCR positive
- •ALT > 40 iu/ml
- •Ishak fibrosis score (within last 5 years) > 2, < 5
- •Informed consent
- •Failed antiviral therapy for HCV in last 5 years
排除标准
- •Patients requiring anticoagulation for existing clinical indications
- •Active peptic ulcer disease
- •Past history of haemorrhagic stroke
- •Thrombocytopaenia (platelets count < 100 x 109 /L)
- •Clinical evidence of portal hypertension
- •Known cerebrovascular abnormalities;
- •HIV antibody positive;
- •Alcohol abuse (>40 unites/week)
- •Menhorragia
- •Pregnancy
研究组 & 干预措施
Warfarin anticoagulation
Anticoagulated with warfarin to maintain an INR of 2-3 between 8 and 16 weeks (treatment period).
干预措施: Warfarin (Drug)
结局指标
主要结局
Median Liver Stiffness Value
时间窗: Baseline (start of the observation period at week 0), 8-weeks (completion of the observation period) and 16-weeks (completion of the period of anticoagulation)
Median liver stiffness at 16-weeks following the 8-week period of anticoagulation, compared to 8-week period of observation. kPa values reported are the values from completion of the period of anticoagulation at week 16 versus completion of the observation period at week 8, and start of the observation period at week 0.
次要结局
- Number of Participants With Adverse Events(8-week period of warfarin treatment and 8-week observation period (16 weeks))