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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：主要目的是评价慢性病毒性肝炎与由于肝毒性而永久停止治疗潜伏性TB感染（LTBI）之间的关系。 次要目的是：描述慢性病毒性肝炎与因肝毒性而暂时停止LTBI治疗之间的关系;描述HIV感染与LTBI治疗期间需要停止治疗的肝毒性之间的关系（在已知HIV血清状态的患者亚组中）;描述与LTBI治疗期间需要停药的肝毒性相关的HIV和HCV感染之间的协同作用;并比较与酒精滥用、慢性病毒性肝炎和/或HIV感染相关的LTBI治疗期间至发生需要停药的肝毒性的时间。 研究报告：在符合研究病例定义的四周内，病例将接受知情同意过程和关于慢性病毒性肝炎的咨询，回答关于酒精和伴随药物摄入的简短问卷，并抽血进行急性和慢性病毒性肝炎筛查。 这将需要将5至10 cc的血液收集在一个标准的红盖管或分离管中，用于储存和运输到CDC。 该试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组将在不迟于第8周研究访视时进行知情同意过程。 在第8周常规研究访视时，受试者将接受有关慢性病毒性肝炎的咨询，回答有关酒精和合并用药摄入的简短问卷，并抽血进行急性和慢性病毒性肝炎筛查。 方法：研究设计是在研究26的入组者中进行的病例队列研究，比较了两种治疗方案对潜伏性TB感染的疗效。 病例为任一治疗组中的临床试验受试者，其研究药物暂停任何时间长度，与以下情况相关：（1）AST大于或等于正常值上限（ULN）3，并伴有肝炎症状或体征;或（2）AST大于5 ULN，伴或不伴肝炎症状或体征，且同意参加本子研究。 在入组母研究时，将随机选择入组研究26的5.5例患者作为子研究的潜在对照。 临床相关性：初步数据表明，慢性病毒性肝炎患者，无论是否合并艾滋病毒感染，在抗结核药物治疗期间，比没有慢性病毒性肝炎的患者经历更多的肝毒性。 目前美国结核病控制的重点是扩大结核菌素的靶向检测和治疗潜伏性结核病感染，这将使慢性病毒性肝炎患者面临这一潜在风险。