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

德克萨斯州莫西沙星对 TB-Study 27 (HIV) 的活性和耐受性评估

• 批准号: 7627502
• 负责人: MARC H WEINER
• 金额: $ 0.8万
• 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/7627502
• 关键词: Adolescent; Adverse event; Age; Brazil; Breast Feeding; Caliber; Chest; Child; Computer Retrieval of Information on Scientific Projects Database; Daily; Dose; Double-Blind Method; Enrollment; Ethambutol; Female; Funding; Gases; Geographic Locations; Grant; Institution; Medicine; Moxifloxacin; North America; Numbers; Patient currently pregnant; Patients; Persons; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Pulmonary Tuberculosis; Pyrazinamide; Randomized; Rate; Research; Research Personnel; Resources; Rifampin; Safety; Source; Sputum; Standards of Weights and Measures; Structure of parenchyma of lung; Thick; Time; Toxic effect; Treatment Failure; Treatment Protocols; Uganda; Uncertainty; United States National Institutes of Health; Upper arm; Visit; Vitamin B6; Week; Woman; day; isoniazid; male; prospective

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：主要目标是比较莫西沙星治疗方案的四毒（密集）阶段的培养转换率与乙酰丁醇方案的治疗阶段，并比较莫克西二糖素治疗方案的安全性和可耐受性与乙醇酚治疗方案的安全性和耐受性。 次要目标是：比较在每日方案四次治疗阶段结束时的培养转换率（每周5天）与间歇性方案（每周三次）；比较每日方案的安全性和耐受性与间歇性方案的安全性；比较感染HIV的患者与艾滋病毒未感染的患者的不良事件；比较莫西沙星方案与乙酰丁醇方案的治疗失败率；并确定是否存在延迟毒性归因于Moxifloxatin（毒性在莫西沙星治疗两个月后变得明显）。 研究计划：该试验将在男性和女性患者（包括受HIV感染者）中进行，他们需要治疗肺结核。 我们不打算为18岁以下的孕妇或母乳喂养妇女，儿童或青少年招募，因为这些患者对莫西法沙星的安全性不确定。 所有研究疗法将通过直接观察到的治疗（DOT）进行。 研究治疗组是： - 每日控制方案：标准结核病药物（INH，利福平，PZA，ethambutol）加上由点5至7天给药的莫西法沙星安慰剂，持续8周。 - 每日莫西沙星治疗方案：莫西法沙星400毫克加标准结核病（INH，利福平，PZA）和ethambutol安慰剂，由点每周5至7天施用8周。 - 间歇性控制方案：标准结核病药物（INH，利福平，PZA，ethambutol）加上由DOT 5至7天施用的Moxifloxacin安慰剂，持续2周，然后每周3次，持续6周。 - 间歇性莫氧霉素方案：Moxifloxatin加标准结核病（INH，Rifampin，PZA）和DOT每周5至7天进行2周，然后每周3次，然后每周3次，再持续6周。 在所有研究臂中，每种剂量都将给予50 mg的毒素（维生素B6）。 合格的患者将以1：1：1：1的比例与四个阶乘臂的比例随机分配。 随机分组将通过注册地理部位（北美，巴西，乌干达）进行分层，并在存在的存在下，定义为含气的Lucent空间，在肺实质中的直径至少1厘米，被浸润或纤维化壁包围，在标准的胸部射频射频散热器上看到了大于1 mm的纤维化壁。 在强化治疗阶段，每2周将每2周看到受试者。 强化治疗阶段的结尾由剂量数量定义：每日治疗疗法的患者为40剂，每天28剂（每天10剂剂量，每周18剂剂量为18剂），用于间歇性方案的患者。 将在研究中遵循患者，直到完成治疗的延续阶段。 每月将在3个月，4个月，5个月和6个月的情况下进行访问。 但是，在强化阶段结束时具有空化和痰液呈阳性的痰液培养的患者需要延长治疗，总计38周（9个月）。 这些患者的研究就诊将在7个月，8个月和9个月时继续进行。 治疗完成后不会遵循患者。 方法：这是一项双盲，安慰剂控制的，多中心的，前瞻性的，随机的研究，以评估使用Moxifloxacin（Moxi）代替ethambutol（e），以及以及异oni剂（H），Rifampin（R），R）和吡azin（Z）的培养基（Z）对2 montion spection spection spection spection contrive spection contression（e）。结核病。