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

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 目的：主要目的是比较利多卡因方案与乙胺丁醇方案的四种药物（强化）治疗期结束时的培养转化率，并比较利多卡因方案与乙胺丁醇方案的安全性和耐受性。 次要目的是：比较每日方案的四种药物治疗期结束时的培养转化率（每周5天）vs.间歇性方案（每周三次）;比较每日方案与间歇方案的安全性和耐受性;比较HIV感染患者与未感染HIV患者的不良事件;比较利沙沙星方案与乙胺丁醇方案的治疗失败率;并确定是否存在利沙沙星引起的延迟毒性（利沙沙星治疗两个月后毒性变得明显）。 研究报告：该试验将在需要肺结核治疗的男性和女性患者中进行，包括艾滋病毒感染者。 我们不计划招募妊娠或哺乳期妇女、儿童或18岁以下青少年，因为在这些患者群体中对阿氟沙星的安全性存在不确定性。 所有研究治疗将通过直接观察治疗（DOT）进行给药。 研究治疗组为： - 每日对照方案：标准TB药物（INH、利福平、PZA、乙胺丁醇）加氟沙星安慰剂，通过DOT每周给药5至7天，持续8周。 - 每日替诺沙星方案：利多卡因400 mg+标准结核药物（INH、利福平、PZA）和乙胺丁醇安慰剂，每周5 - 7天，共8周。 - 间歇性对照方案：标准TB药物（INH、利福平、PZA、乙胺丁醇）加氟沙星安慰剂，通过DOT每周给药5至7天，持续2周，然后每周给药3次，持续6周。 - 间歇性阿氟沙星方案：利多卡因加标准结核药物（INH、利福平、PZA）和乙胺丁醇安慰剂，DOT每周给药5 - 7天，持续2周，然后每周给药3次，持续6周。 在所有研究组中，每次给药时给予吡哆醇（维生素B6）50 mg。 合格患者将以1：1：1：1的比例随机分配至4个因子组。 随机化将按照入组的地理位置（北美、巴西、乌干达）和是否存在空洞进行分层，空洞定义为肺实质内直径至少1 cm的含气体透明空间，周围有浸润或纤维化壁，厚度大于1 mm，见于标准胸片。 在强化治疗阶段，将每2周一次对受试者进行访视。 强化治疗期结束定义为给药次数：每日给药方案患者40次给药，间歇给药方案患者28次给药（10次每日给药，18次每周三次给药）。 将在研究中对患者进行随访，直至完成治疗的继续阶段。 将在3个月、4个月、5个月和6个月时每月进行访视。 然而，在强化阶段结束时有空洞和痰培养阳性的患者将需要总共38周（9个月）的延长治疗。 这些患者的研究访视将继续在7个月、8个月和9个月时进行。 治疗完成后将不对患者进行随访。 方法：这是一项双盲、安慰剂对照、多中心、前瞻性、随机研究，旨在评价使用氟诺沙星（Moxi）代替乙胺丁醇（E），与异烟肼（H）、利福平（R）和吡嗪酰胺（Z）联合使用对痰涂片阳性肺结核患者2个月培养转换的影响。

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.