IMPACT OF CHRONIC VIRAL HEPATITIS ON PT D/C OF TX FOR LATENT TB-STUDY 26A (HIV)

慢性病毒性肝炎对 TX 潜伏结核病 PT D/C 的影响-研究 26A (HIV)

• 批准号: 7627499
• 负责人: MARC H WEINER
• 金额: $ 0.53万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627499
• 关键词: Acute; Alcohol abuse; Alcohols; Antitubercular Agents; Blood; Centers for Disease Control and Prevention (U.S.); Chronic; Chronic viral hepatitis; Clinical Trials; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Consent; Counseling; Data; Enrollment; Funding; Grant; HIV; HIV Infections; Hepatitis; Hepatitis C; Hepatotoxicity; Infection; Informed Consent; Institution; Intake; Length; Parents; Participant; Patients; Persons; Pharmaceutical Preparations; Population; Process; Questionnaires; Research; Research Design; Research Personnel; Resources; Risk; Screening procedure; Shipping; Ships; Source; Standards of Weights and Measures; Symptoms; Testing; Time; Treatment Protocols; Tube; Tuberculin; United States National Institutes of Health; Upper Limit of Normal; Upper arm; Viral; Visit; Week; clinically relevant; experience; synergism; tuberculosis drugs

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The primary objective is to evaluate the association between chronic viral hepatits and permanent discontinuation of treatment for latent TB infection (LTBI) due to hepatotoxicity. Secondary objectives are: to describe the association between chronic viral hepatitis and temporary discontinuation of treatment for LTBI due to hepatotoxicity; to describe the association of HIV infection with hepatotoxicity requiring treatment discontinuation during treatment for LTBI (among the subset of patients with known HIV serostatus); to describe the synergism between HIV and HCV infection associated with hepatotoxicity requiring treatment discontinuation during treatment for LTBI; and to compare the time to onset of hepatotoxicity requiring treatment discontinuation during treatment for LTBI that is associated with alcohol abuse, chronic viral hepatitis, and/or HIV infection. RESEARCH PLAN: Cases, within four weeks of the time they fulfill the study definition of a case, will undergo the informed consent process and counseling regarding chronic viral hepatitis, answer a brief questionnaire regarding alcohol and concomitant medication intake, and have blood drawn for screening for acute and chronic viral hepatitis. This will require 5 to 10 cc of blood to be collected in one standard red top tube or separator tube, for storage and shipping to CDC. This tube is in addition to any testing the local clinician is conducting. Controls who agree to participate in the sub-study will undergo the informed consent process no later than the Week 8 study visit. At the Week 8 routine study visit, they will undergo counseling regarding chronic viral hepatitis, answer a brief questionnaire regarding alcohol and concomitant medication intake, and have blood drawn for screening for acute and chronic viral hepatitis. METHODS: The study design is a case-cohort study within enrollees in Study 26, which compares the efficacy of two treatment regimens for latent TB infection. A case is a clinical trial participant in either treatment arm who has study drug(s) held for any length of time associated with: (1) AST greater than or equal to 3 the upper limit of normal (ULN) and symptoms or signs of hepatitis; or (2) AST greater than 5 ULN with or without symptoms or signs of hepatitis, and who consents to be in this sub-study. Five and one-half percnt of patients enrolling in Study 26 will be randomly selected as potential controls for the sub-study at the time of enrollment in the parent study. CLINICAL RELEVANCE: Preliminary data suggst that persons with chronic viral hepatitis, with or without HIV co-infection, experience more hepatotoxicity during treatment with anti-tuberculosis drugs than do those without chronic viral hepatitis. The current U.S. TB control emphasis on expanding targeted tuberculin tesing and treatment of latent TB infection will expose populations with chronic viral hepatitis to this potential risk.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：主要目的是评估慢性病毒性肝炎与因肝毒性而永久停止治疗潜伏性结核感染（LTBI）之间的关系。 次要目标是：描述慢性病毒性肝炎与因肝毒性而暂时停止 LTBI 治疗之间的关联；描述 HIV 感染与肝毒性之间的关联，需要在 LTBI 治疗期间停止治疗（在已知 HIV 血清状态的患者子集中）；描述 HIV 和 HCV 感染之间的协同作用，与 LTBI 治疗期间需要停止治疗的肝毒性相关；比较与酗酒、慢性病毒性肝炎和/或 HIV 感染相关的 LTBI 治疗期间出现肝毒性（需要停止治疗）的时间。 研究计划：病例在满足病例研究定义后的四个星期内，将接受有关慢性病毒性肝炎的知情同意程序和咨询，回答有关酒精和伴随药物摄入的简短调查问卷，并抽血筛查急性和慢性病毒性肝炎。 这需要将 5 至 10 cc 的血液收集到一根标准红顶管或分离管中，以便储存并运送到 CDC。 该管是当地临床医生正在进行的任何测试的补充。 同意参加子研究的对照者将在不迟于第 8 周研究访视时接受知情同意程序。 在第 8 周的例行研究访视中，他们将接受有关慢性病毒性肝炎的咨询，回答有关酒精和伴随药物摄入的简短调查问卷，并抽血筛查急性和慢性病毒性肝炎。 方法：该研究设计是一项针对研究 26 参与者的病例队列研究，比较了两种治疗方案对潜伏性结核感染的疗效。 病例是任一治疗组的临床试验参与者，其持有研究药物的时间与以下情况相关：(1) AST 大于或等于 3 正常上限 (ULN)，并且有肝炎症状或体征； (2) AST 大于 5 ULN，有或没有肝炎症状或体征，并且同意参加本子研究。 在参加母研究时，将随机选择参加研究 26 的百分之五点五的患者作为子研究的潜在对照。 临床相关性：初步数据表明，患有慢性病毒性肝炎的人，无论是否合并感染艾滋病毒，在抗结核药物治疗期间比没有慢性病毒性肝炎的人经历更多的肝毒性。 目前美国结核病控制重点是扩大有针对性的结核菌素检测和潜在结核感染的治疗，这将使慢性病毒性肝炎患者面临这种潜在风险。