The North Carolina Hepatitis Beta Clinical Research Network

北卡罗来纳州乙型肝炎临床研究网络

• 批准号: 8545812
• 负责人: MICHAEL W FRIED
• 金额: $ 34.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545812
• 关键词: Adherence; Antiviral Agents; Antiviral Response; Antiviral Therapy; Antiviral resistance; Appearance; Biological Assay; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Collaborations; Combined Modality Therapy; Comorbidity; Data; Databases; Detection; Disadvantaged; Disease Progression; Eligibility Determination; Enrollment; Ensure; Equilibrium; Evolution; Future; Guidelines; Health Insurance Portability and Accountability Act; Hepatitis; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Therapy; Hepatitis B Virus; Hepatitis B e Antigens; Immunology; Incidence; Individual; Institutional Review Boards; Liver; Liver diseases; Longitudinal Studies; Measures; Medical; Medical center; Methods; Minor; Multicenter Trials; Mutation; Natural History; North Carolina; Outcome; Participant; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phenotype; Population; Primary carcinoma of the liver cells; Principal Investigator; Protocols documentation; Publishing; Race; Recommendation; Regimen; Registries; Relative (related person); Research; Research Design; Resistance; Resistance development; Risk; Risk Factors; Role; Safety; Sampling; Serological; Serum; Site; Source; Specimen; Tenofovir; Testing; Therapeutic; Tissues; Universities; Variant; Viral; Viremia; Virus; arm; cohort; cooperative study; data sharing; design; entecavir; epidemiologic data; experience; follow-up; insight; intrahepatic; meetings; member; novel; novel marker; patient population; prevent; programs; repository; response; therapy development; translational study; viral resistance; virology

DESCRIPTION (provided by applicant): The optimal treatment for chronic hepatitis B remains controversial. Published guidelines from several sources suggest initiating antiviral therapy, in general, when serum ALT activity is abnormal and when significant liver disease is present. These recommendations have largely been developed by balancing the likelihood of response as measured in short-term studies against the likelihood of developing viral resistance during extended therapy. However, these guidelines have never been prospectively evaluated to determine whether they truly represent the best strategy for selecting candidates for treatment. Furthermore, recent epidemiologic data indicate that the presence of high level HBV viremia itself is an important risk factor for subsequent cirrhosis and hepatocellular carcinoma, suggesting that rigid adherence to treatment guidelines may disadvantage many patients for whom long-term viral suppression may be beneficial. The current availability of multiple potent antiviral agents with good safety profiles and a seemingly low risk of resistance provide an opportunity to optimize strategies to treat chronic hepatitis B. This proposal will focus on the design of 1) a research database and specimen repository and 2) a collaborative multicenter trial to corroborate current treatment guidelines while comparing the long-term efficacy and safety of monotherapy vs. combination therapy. The study design will further refine the identification and management of hepatitis B viral resistance during extended therapy, and provide important information regarding the long-term outcomes associated with treatment. Our proposal to participate as a Clinical Center for this cooperative study will emphasize the experience, unique attributes, and patient population of the Liver Program at the University of North Carolina at Chapel Hill, in collaboration with Duke University, and Carolinas Medical Center, which will ensure successful completion of these studies as a member of the Hepatitis B Clinical Research network.

描述（由申请人提供）：慢性乙型肝炎的最佳治疗仍然有争议。通常，当血清ALT活性异常且存在明显的肝病时，来自多个来源的已发表的指南表明，开始抗病毒疗法。这些建议在很大程度上是通过平衡在短期研究中衡量的反应的可能性与在扩展治疗过程中发展病毒抗性的可能性的基础提出的。但是，这些准则从未经过前瞻性评估，以确定它们是否真正代表了选择治疗候选者的最佳策略。此外，最近的流行病学数据表明，高水平的HBV病毒血症本身是随后的肝硬化和肝细胞癌癌的重要危险因素，这表明对治疗指南的严格依从性可能会损害许多患者的许多患者，这些患者对他们来说可能是有益的。目前，具有良好安全性和抵抗风险的多种有效抗病毒剂的可用性为优化治疗慢性乙型肝炎的策略提供了机会。 该建议将重点介绍1）研究数据库和标本存储库的设计，以及2）一项协作多中心试验，以证实当前的治疗指南，同时比较单药治疗与组合治疗的长期疗效和安全性。研究设计将进一步完善肝炎在扩展治疗过程中的抗性病毒抗性的识别和管理，并提供有关与治疗相关的长期结局的重要信息。我们将作为这项合作研究的临床中心参与的建议将强调北卡罗来纳大学教堂山分校的肝脏计划的经验，独特的属性和患者人群，并与杜克大学和卡罗来纳州医疗中心合作，这将确保成功完成这些研究成员作为肝炎B临床研究网络的成员。