CLINICAL TRIAL: RIFAPENTINE/ISONIAZID FOR 3 MONTHS VS 9 MO FOR LATENT TB (STUDY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：主要目的是评价利福喷丁加异烟肼(3RPT/INH)每周3个月、12剂方案(3RPT/INH)与9个月、每天270剂异烟肼(9INH)方案在预防高危结核菌素皮试反应中预防结核病的有效性。次要目标是：比较因药物不良反应或与3RPT/INH和9INH有关的任何原因而停药的比率；比较与3RPT/INH和9INH有关的任何3、4或5级药物毒性的比率；比较3RPT/INH和9INH的治疗完成率；比较3RPT/INH和9INH在完成研究阶段治疗的人中的疗效；比较3RPT/INH和9INH在艾滋病毒感染者中的有效性和耐受性；比较同时接受美沙酮治疗的人中与3RPT/INH和9INH有关的美沙酮停药比率；并描述尽管接受潜伏感染治疗但仍发展为结核病的患者中结核分枝杆菌分离株的耐药性模式。 研究计划：这项试验将在包括艾滋病毒感染者在内的高风险结核菌素皮试反应者中进行，这些人需要治疗潜伏感染以预防结核病。我们不打算在这个网站招收18岁以下的儿童或青少年。每周的利福喷丁(体重超过50公斤者为900毫克，体重在50公斤或以下者为750毫克)和异烟肼(15毫克/公斤)方案将在直接观察下服用，每天的异烟肼(5毫克/公斤)方案将主要自我给药。在两个研究组中，每一剂量的异烟肼都将给予50毫克的吡哆醇(维生素B6)。密切接触者将按家庭随机分配；其他人将单独随机分配。所有参与者在研究阶段治疗开始后将被跟踪33个月。在研究阶段的治疗期间，受试者将每四周接受一次检查。治疗后的随访将每三个月进行一次，直到登记后21个月，此后每六个月进行一次。 方法：这是一项开放、多中心、前瞻性、随机的研究，目的是评价3RPT/INH与9INH的有效性，比较9INH在需要治疗潜伏感染以预防结核病的高危结核菌素皮试反应中的有效性。

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 effectiveness of a three-month, 12-dose regimen of weekly rifapentine plus isoniazid (3RPT/INH) compared to the effectiveness of a nine-month, 270 dose regimen of daily isoniazid (9INH) in preventing TB in high-risk tuberculin skin-test reactors. Secondary objectives are: to compare the rates of drug discontinuation due to adverse drug reactions or for any reason associated with 3RPT/INH and 9INH; to compare the rates of any grade 3, 4, or 5 drug toxicity associated with 3RPT/INH and 9INH; to compare treatment completion rates of 3RPT/INH and 9INH; to compare the efficacy of 3RPT/INH and 9INH among persons who complete study-phase therapy; to compare the effectiveness and tolerability of 3RPT/INH and 9INH in HIV-infected persons; to compare the rates of methadone withdrawal associated with 3RPT/INH and 9INH among persons concomitantly receiving methadone; and to describe patterns of antibiotic resistance among Mycobacterium tuberculosis isolates in patients who develop tuberculosis despite treatment of latent infection. RESEARCH PLAN: This trial will be conducted among high-risk tuberculin skin-test reactors, including HIV-infected persons, who require treatment of latent infection to prevent tuberculosis. We do not plan to enroll children or adolescents under the age of 18 at this site. The weekly rifapentine (900 mg for persons weighing more than 50 kg or 750 mg for persons weighing 50 kg or less) and isoniazid (15 mg/kg) regimen will be given under direct observation and the daily isoniazid (5 mg/kg) regimen will be primarily self-administered. Pyridoxine (vitamin B6) 50 mg will be given with each dose of isoniazid in both study arms. Close contacts will be randomized by household; others will be randomized individually. All participants will be followed for 33 months after initiation of study-phase therapy. Subjects will be seen every four weeks during study-phase therapy. Post-therapy follow-up will occur every three months until 21 months after enrollment, and every six months thereafter. METHODS: This is an open-label, multi-center, prospective, randomized study to evaluate the effectiveness of 3RPT/INH compared to the effectiveness of 9INH conducted among high-risk tuberculin skin-test reactors who require treatment of latent infection to prevent tuberculosis.