PILOT STUDY OF PIRFENIDONE IN PBC AND PSC

吡非尼酮在 PBC 和 PSC 中的试点研究

• 批准号: 2596077
• 负责人: Keith D Lindor
• 金额: $ 6.4万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-25 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2596077
• 关键词: alanine transaminase; albumins; alkaline phosphatase; aspartate transaminase; biliary tract disorder chemotherapy; bilirubin; cholangiography; clinical research; enzyme activity; fibrinolysis; fibrinolytic agents; human subject; human therapy evaluation; inhibitor /antagonist; portal hypertension; primary biliary cirrhosis; prothrombin time; pruritis; sclerosis; transforming growth factors

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are progressive chronic cholestatic liver diseases. Many patients eventually develop cirrhosis and/or portal hypertension with death caused by hepatic failure unless liver transplantation intervenes. No specific therapy has been proven to be totally effective in these diseases. Ursodeoxycholic acid (UDCA) is the most promising drug for patients with PBC but some patients still develop complications of their liver disease and require liver transplantation. There is no effective medical therapy for PSC despite evaluation of several drugs. It is clear therefore, that further clinical trials evaluating new drug in the treatment of PBC and PSC are needed. Transforming growth factor-beta 1 (TGF-B1), a growth cytokine, has a key role in the development of experimental biliary and hepatic fibrosis in animal models. Pirfenidone, a TGF-B 1 antagonist, is a promising new antifibrotic drug that has been evaluated in experimental and clinical trials in the treatment of other non-hepatic disease characterized by excessive fibrosis. The aims of this pilot study are: (1) to monitor the safety profile of pirfenidone in patients with PBC and PSC, (2) to compare the effects of pirfenidone to baseline values on symptoms, liver biochemistries and the development of complications of liver disease, and (3) to evaluate the clinical antifibrotic activity of pirfenidone on portal hypertension (hepatic venous pressure gradient and gastroesophageal varices) in portal hypertensive patients with PBC and on the severity of bile duct fibrosis/sclerosis in patients with PSC. Twenty PBC patients with portal hypertension and twenty patients with PSC will be treated with pirfenidone 800 mg p.o. tid for at least one and up to two years. Baseline values will be compared to those observed after treatment for one year. Promising results will encourage us to test this agent alone or in combination with other drugs in future large scale randomized controlled trials. Our ultimate aim is to be able to offer these patients safe and effective therapy for their liver disease, a goal which we have not yet achieved.

原发性胆道肝硬化（PBC）和原发性硬化胆管炎（PSC） 是进行性慢性胆汁淤积性肝病。 许多患者 最终随着死亡而形成肝硬化和/或门户高血压 除非肝移植干预，否则是由肝衰竭引起的。 不 事实证明，特定的疗法在这些方面完全有效 疾病。 ursoxyoxycholic（UDCA）是最有前途的药物 患有PBC的患者，但有些患者仍会出现并发症 肝病，需要肝移植。 没有有效 尽管评估了几种药物，但用于PSC的药物治疗。 这是 因此，清楚地表明，进一步评估新药的临床试验 需要对PBC和PSC进行处理。 转化生长因子β 1（TGF-B1），一种生长细胞因子，在发展中具有关键作用 动物模型中的实验性胆道和肝纤维化。 Pirfenidone是TGF-B 1拮抗剂，是一种有希望的新抗纤维化药物 在实验和临床试验中已评估 其他非肝病的治疗 纤维化。 该试点研究的目的是：（1）监视安全 PIRFENIDONE在PBC和PSC患者中的特征，（2）比较 吡非酮对基线值对症状，肝脏的影响 生物化学和肝病并发症的发展， （3）评估Pirfenidone的临床抗纤维化活性 在门户高血压（肝静脉压力梯度和 PBC和PBC和 关于PSC患者的胆管纤维化/硬化症的严重程度。 二十名PBC病人高血压患者和20例患者 PSC将用Pirfenidone 800 mg P.O进行处理。至少一个 最多两年。 将基线值与观察到的值进行比较 治疗后一年。 有希望的结果将鼓励我们 单独测试该试剂或将来与其他药物结合使用 比例随机对照试验。我们的最终目标是能够 为这些患者提供安全有效的肝病治疗， 我们尚未实现的目标。