AN EVAL OF ACTIVITY AND TOLERABILITY OF MOXIFLOXACIN IN TX FOR TB-STUDY 27 (HIV)

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：比较莫西沙星方案与乙胺丁醇方案在四药(强化)治疗结束时的培养转换率，比较莫西沙星方案与乙胺丁醇方案的安全性和耐受性。次要目标是：比较每日方案(每周5天)和间歇方案(每周3次)在四个药物治疗阶段结束时的培养转换率；比较每日方案和间歇方案的安全性和耐受性；比较艾滋病毒感染患者和未感染艾滋病毒患者的不良事件；比较莫西沙星方案和乙胺丁醇方案的治疗失败率；以及确定莫西沙星是否有延迟毒性(毒性在莫西沙星治疗两个月后显现)。 研究计划：这项试验将在需要治疗肺结核的男性和女性患者中进行，包括艾滋病毒感染者。我们不打算招募怀孕或哺乳的妇女、儿童或18岁以下的青少年，因为不确定莫西沙星在这些患者组中的安全性。所有研究治疗将通过直接观察治疗(DOT)进行。研究治疗组包括： -每日控制方案：标准结核病药物(异烟肼、利福平、PZA、乙胺丁醇)加莫西沙星安慰剂，DOT每周5至7天，共8周。 -莫西沙星每日方案：莫西沙星400 mg加标准结核病药物(异烟肼、利福平、PZA)和乙胺丁醇安慰剂，DOT每周5至7天，共8周。 -间歇控制方案：标准结核病药物(异烟肼、利福平、PZA、乙胺丁醇)加莫西沙星安慰剂，DOT每周5-7天，持续2周，然后每周3次，持续6周。 -莫西沙星间歇性方案：莫西沙星加标准结核病药物(异烟肼、利福平、PZA)和乙胺丁醇安慰剂，DOT每周5-7天，持续2周，然后每周3次，持续6周。 在所有研究人员中，每一剂量都将给予50毫克的吡哆醇(维生素B6)。符合条件的患者将以1：1：1：1的比例随机分为四个因素组。随机分组将按登记的地理地点(北美、巴西、乌干达)和是否存在空洞进行分层，空洞的定义是肺实质内直径至少1厘米的含气体朗讯空间，周围是标准胸片上看到的大于1毫米厚的浸润壁或纤维壁。在强化治疗阶段，受试者将每两周接受一次检查。强化治疗阶段的结束以剂量数来定义：每日方案的患者为40剂，间歇方案的患者为28剂(每天10剂，每周18次)。患者将在研究中接受跟踪，直到完成继续治疗阶段。每月访问3个月、4个月、5个月和6个月。然而，在强化阶段结束时出现空洞和痰培养阳性的患者将需要延长治疗总计38周(9个月)。这些患者的研究访问将继续在7个月、8个月和9个月进行。治疗结束后，患者将不再接受随访。 方法：采用双盲、安慰剂对照、多中心、前瞻性、随机化研究，评价莫西沙星(Moxi)替代乙胺丁醇(E)与异烟肼(H)、利福平(R)、吡津胺(Z)联合应用对痰涂阳肺结核患者2个月培养转换率的影响。

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 objectives are to compare the culture-conversion rate at the end of the four-drug (intensive) phase of therapy of the moxifloxacin regimens vs. that of the ethambutol regimens and to compare the safety and tolerability of the moxifloxacin regimens to that of the ethambutol regimens. Secondary objectives are: to compare the culture-conversion rate at the end of the four-drug phase of therapy of the daily regimens (5 days per week) vs. the intermittent regimens (thrice-weekly); to compare the safety and tolerability of the daily regimens to that of the intermittent regimens; to compare adverse events among HIV-infected patients vs. HIV-uninfected patients; to compare the rates of treatment failure of the moxifloxacin regimens to the ethambutol regimens; and to determine whether there is delayed toxicity attributable to moxifloxacin (toxicity that becomes evident after the two months of moxifloxacin therapy). RESEARCH PLAN: This trial will be conducted among male and female patients, including HIV-infected persons, who require treatment for pulmonary tuberculosis. We do not plan to enroll pregnant or breast-feeding women, children, or adolescents under the age of 18 because of uncertainties about the safety to moxifloxacin in those groups of patients. All study therapy will be administered by direct observed therapy (DOT). The study treatment groups are: - Daily control regimen: standard TB medicines (INH, rifampin, PZA, ethambutol) plus moxifloxacin placebo administered by DOT 5 to 7 days per week for 8 weeks. - Daily moxifloxacin regimen: moxifloxacin 400 mg plus standard TB medicines (INH, rifampin, PZA) and ethambutol placebo administered by DOT 5 to 7 days per week for 8 weeks. - Intermittent control regimen: standard TB medicines (INH, rifampin, PZA, ethambutol) plus moxifloxacin placebo administered by DOT 5 to 7 days a week for 2 weeks, then 3 times a week for 6 more weeks. - Intermittent moxifloxacin regimen: moxifloxacin plus standard TB medicines (INH, rifampin, PZA) and ethambutol placebo administered by DOT 5 to 7 days a week for 2 weeks, then 3 times a week for 6 more weeks. Pyrodoxine (vitamin B6) 50 mg will be given with each dose in all study arms. Eligible patients will be randomized in a 1:1:1:1 ratio to the four factorial arms. Randomization will be stratified by geographic site of enrollment (North America, Brazil, Uganda) and by the presence of cavitation, defined as a gas-containing lucent space at least 1 cm in diameter within the lung parenchyma surrounded by an infiltrate or fibrotic wall greater than 1 mm thick seen on a standard chest radiograph. Subjects will be seen every 2 weeks during the intensive therapy phase. End of intensive therapy phase is defined by number of doses: 40 doses for patients on daily regimen and 28 doses (10 daily doses, 18 thrice-weekly doses) for patients on intermittent regimen. Patients will be followed in the study until completion of the continuation phase of therapy. Visits will occur every month at 3 months, 4 months, 5 months, and 6 months. However, patients who have cavitation and a positive sputum culture at the end of the intensive phase will require extended therapy for a total of 38 weeks (9 months). Study visits for these patients will continue to occur at 7 months, 8 months, and 9 months. Patients will not be followed after the completion of therapy. METHODS: This is a double-blind, placebo-controlled, multi-center, prospective, randomized study to evaluate the effect of using moxifloxacin (Moxi) in place of ethambutol (E), in combination with isoniazid (H), rifampin(R), and pyrazinamide (Z) on 2-months culture conversion among patients with sputum smear-positive pulmonary tuberculosis.