A prospective, randomized, clinical trial to evaluate two novel therapies, mycoph

一项评估两种新疗法 mycoph 的前瞻性随机临床试验

• 批准号: 8914475
• 负责人: TIMOTHY ROSS MORGAN
• 金额: $ 67.75万
• 依托单位: SOUTHERN CALIFORNIA INST FOR RES/EDUC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8914475
• 关键词: Acute Alcoholic Hepatitis; Adverse event; Age; Albumins; Alcoholic Hepatitis; Bilirubin; Blood specimen; Cessation of life; Chronic; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Creatinine; Crohn' s disease; Data; Data Analyses; Disease; Hepatic; Immunologics; Immunosuppressive Agents; Infection; Inflammation; Inflammatory; Injury; Interleukin-1; Lead; Liver; Liver diseases; Lymphocyte; Lymphocyte Function; Macrophage Activation; Measures; Minority; Monitor; Mycophenolate; Natural regeneration; Oral; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Proteomics; Psoriasis; Randomized Clinical Trials; Reporting; Research Project Grants; Rheumatoid Arthritis; Serum; Steroids; Symptoms; Syndrome; Systems Biology; Testing; Translational Research; cytokine; design; effective therapy; efficacy testing; improved; liver function; liver inflammation; liver injury; mortality; mycophenolate mofetil; novel; peripheral blood; prednisolone; primary outcome; problem drinker; prospective; response; secondary outcome; standard of care; transcriptomics; treatment duration

DESCRIPTION (provided by applicant): Alcoholic hepatitis is an inflammatory disease of the liver that occurs for unknown reasons in a minority of chronic alcoholics. Inflammation is the underlying cause of liver injury and the cause of symptoms and death. Prednisolone, the most commonly recommend treatment, improves survival in most, but not all, patients. In particular, prednisolone does not improve survival among patients with a Lille score e0.45. To improve overall survival in alcoholic hepatitis, new treatments are needed for patients who fail to respond to prednisolone. We propose to evaluate two drugs in alcoholic hepatitis. First, we will test rilonacept, a drug directed against the pro- inflammatory cytokine, interleukin-1, in patients with a Lille score <0.45 (responders to prednisolone). Because these patients have an excellent survival with prednisolone treatment (standard of care treatment), we will determine whether the addition of rilonacept for three weeks (rilonacept+prednisolone) will result in a more rapid improvement in serum bilirubin (a measure of liver function). Second, we will test the mycophenolate, a drug directed against lymphocytes, among patients with a Lille score e0.45. Because these patients have a 25% mortality at 1 month (and 75% mortality at 6 months), the primary outcome will be a reduction in 28-day mortality among patients receiving prednisolone+mycophenolate as compared with no treatment (standard of care). Use of a prednisolone+mycophenolate is designed to markedly reduce hepatic inflammation in patients who do not respond to prednisolone. Because the combination of prednisolone+mycophenolate is a potent immunosuppressant, patients will be monitored closely for infection and all infections will be reported promptly to a Data Safety Monitoring Board. This clinical trial is a component of a large, translational research project that will investigate liver inflammation, hepatocellular injury and regeneration using immunohistology, immunologic studies of peripheral blood, liver transcriptomics, liver proteomics and a systems biology approach to data analysis. This clinical trial and the associated translational projects will lead to a better understanding of the inflammatory pathways involved and provide data for potential new treatments for alcoholic hepatitis

描述（由申请人提供）：酒精性肝炎是一种肝脏炎症性疾病，发生在少数慢性酗酒者中，原因不明。炎症是肝损伤的根本原因，也是症状和死亡的原因。强的松龙是最常被推荐的治疗方法，它能提高大多数（但不是全部）患者的生存率。特别是，强的松龙不能提高里尔评分为0.45的患者的生存率。为了提高酒精性肝炎患者的总体生存率，需要对治疗无效的患者采用新的治疗方法