VIRAHEP-C Clinical Center

VIRAHEP-C 临床中心

• 批准号: 6407085
• 负责人: HARI S CONJEEVARAM
• 金额: $ 22.91万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6407085
• 关键词: African American; caucasian American; chronic disease /disorder; combination chemotherapy; cooperative study; drug resistance; genetic susceptibility; hepatitis C; human subject; human therapy evaluation; immunotherapy; interferon alpha; liver disorder chemotherapy; patient oriented research; pharmacogenetics; prognosis; racial /ethnic difference; ribavirin; virus genetics; virus load

DESCRIPTION (provided by applicant): Chronic hepatitis C is the leading cause of chronic liver disease and cirrhosis in the United States and is now the leading cause for liver transplantation due to end-stage liver disease. Approximately 1.8% of population (4 million) in the United States have antibody to hepatitis C virus (anti-HCV) and approximately 2.7 million Americans have evidence of chronic infection. The prevalence of antibody to HCV is higher among African Americans (3.2%) than among the non-Hispanic whites (1.8%). Treatment of chronic hepatitis C remains problematical and unsatisfactory. Interferon (IFN) monotherapy given as three times weekly injections has been shown to have biochemical, virological and histological beneficial effects. However, sustained virological response (SVR) is seen in only a minority of patients (6-16%). Treatment with combination of IFN + and ribavirin for 24 or 48 weeks results in SVR rates of up to 35 to 43% respectively. Very limited published data is currently available on the impact of race on response to antiviral therapy in patients with chronic hepatitis C. Most available reports show that African Americans have a significantly lower SVR when compared to non-Hispanic whites with all treatment regimens. We are proposing a multicenter, controlled clinical trial of combination therapy of pegylated interferon + ribavirin for African Americans and non-Hispanic whites chronically infected with HCV genotype 1 virus. Treatment will be administered for a total duration of 48 weeks with a 48-week follow-up post completion of therapy. A total of 400 patients with equal numbers of Caucasians and African Americans (200 in each group) will be enrolled into this study. The primary end-point of this trial is to determine rate of SVR among African Americans and non-Hispanic whites. In addition, factors predictive for a favorable response and patterns of virological response will also be assessed in the two racial groups. The objectives of this trial are to evaluate: (a) the rates of SVR among African Americans and non-Hispanic Whites with chronic hepatitis C after treatment with combination therapy using pegylated interferon and ribavirin for 48 weeks; (b) the factors that are predictive of a SVR to combination therapy in each of the two racial groups and factors associated with poorer response in African Americans and (c) the patterns of virological response (including viral kinetics) early during treatment and determine if different responses predict the ultimate outcome (sustained response, relapse or a lack of response) in each of the two racial groups. The findings of this study will allow us to develop specific algorithms to predict rates of SVR to therapy among African Americans based on their pre-treatment characteristics and patterns of virological response during therapy.

描述（由申请人提供）： 慢性丙型肝炎是导致慢性肝病和肝硬化的主要原因 在美国，现在是肝移植的主要原因， 到晚期肝病约占人口的1.8%（400万）， 美国有丙型肝炎病毒抗体（抗HCV）， 2.7数百万美国人有慢性感染的证据。之时尚 非裔美国人（3.2%）的HCV抗体高于非裔美国人（3.2%）。 非西班牙裔白人（1.8%）。慢性丙型肝炎的治疗 有问题的和不满意的。干扰素（IFN）单药治疗分为三组 每周注射5次已被证明具有生物化学、病毒学和 组织学有益效果。持续病毒学应答（SVR） 仅在少数患者中可见（6 - 16%）。结合治疗 IFN+和利巴韦林治疗24或48周后，SVR率高达35 - 43% 分别目前关于影响的公开数据非常有限 慢性丙型肝炎患者抗病毒治疗反应的种族差异 大多数现有的报告显示，非洲裔美国人有一个显着降低 所有治疗方案与非西班牙裔白人相比的SVR。我们 提出一项多中心、对照的联合治疗临床试验， 聚乙二醇干扰素+利巴韦林用于非裔美国人和非西班牙裔白人 慢性感染HCV基因型1病毒。将给予治疗 总持续时间为48周，完成后进行48周随访 疗法共有400名患者，白人和非洲人的数量相等 美国人（每组200人）将入组本研究。主 本试验的终点是确定非裔美国人的SVR率， 非西班牙裔白人此外，有利反应的预测因素 和病毒学应答模式也将在两个种族中进行评估。 组本试验的目的是评价：（a）SVR率 在非裔美国人和非西班牙裔白人慢性丙型肝炎患者中， 使用聚乙二醇化干扰素和利巴韦林的联合疗法治疗 48周;（B）预测联合治疗的SVR的因素 在两个种族群体中的每一个和与反应较差相关的因素， 非裔美国人和（c）病毒学应答模式（包括病毒 动力学），并确定不同的反应是否预测 最终结局（持续缓解、复发或无缓解） 两个种族的人。这项研究的结果将使我们能够 开发特定的算法来预测非洲人的SVR治疗率 美国人根据他们的治疗前的特点和模式， 治疗期间的病毒学反应