Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial.
Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial.
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DOI：
10.1016/s0140-6736(09)60333-0
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发表时间：
2009-04-04
期刊：
影响因子：
168.9
通讯作者：
Chaisson, Richard E.
中科院分区：
文献类型：
--
作者：
Conde, Marcus B.;Efron, Anne;Laredo, Carla;Muzy De Souza, Gilvan R.;Graca, Nadja P.;Cezar, Michelle C.;Ram, Malathi;Chaudhary, Mohammad A.;Bishai, William R.;Kritski, Afranio L.;Chaisson, Richard E.
需要新的疗法来缩短治愈结核病和治疗耐药菌株所需的时间。氟喹诺酮类药物莫西沙星是一种很有前景的新药，可能对现有的抗结核药物具有附加活性。我们进行了二期临床试验，以确定莫西沙星在结核病治疗初期的活性和安全性。我们在巴西的痰涂片阳性肺结核患者中进行了一项含有莫西沙星方案的随机双盲试验。所有参与者都接受了标准剂量的异烟肼、利福平和吡嗪酰胺治疗，并被随机分为莫西沙星或乙胺丁醇和匹配的安慰剂，每周五天，持续八周。主要终点是第8周痰培养转为阴性的患者的比例。临床试验识别符：NCT00082173。170名患者入选，146名患者符合所有研究资格标准。在一项意向治疗分析中，遗漏的结果被认为是治疗失败，分配给莫西沙星的59名患者(80%)将他们8周的痰培养转为阴性，而分配给乙胺丁醇的患者有45名(63%)(p=0.03)。在第8周有细菌可用的患者中，莫西沙星的转换率为92%(59/)，乙胺丁醇为72%(45/61)(p=0.006)。未观察到毒性差异。在多因素分析中，年龄较小(优势比0.98，p=0.0 5)、基础痰涂片阳性率高(OR0.45，p<；0.001)和接受莫西沙星治疗(OR1.88，p<；0.001)与痰培养转换显著相关。在结核病治疗的初始阶段，莫西沙星显著提高了培养转化率。评估莫西沙星是否可以用来缩短结核病治疗时间的试验是合理的。
New therapies are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains. The fluoroquinolone moxifloxacin is a promising new agent that may have additive activity to existing antituberculosis agents. We conducted a Phase 2 clinical trial to determine the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment. We performed a randomized, double-blind trial of a moxifloxacin-containing regimen in patients with sputum smear-positive tuberculosis in Brazil. All participants received isoniazid, rifampin and pyrazinamide at standard doses and were randomized to receive either moxifloxacin or ethambutol and matching placebos five days per week for eight weeks. The primary endpoint was the proportion of patients whose sputum culture converted to negative by Week 8. Clinical trial identifier: NCT00082173. One hundred seventy patients were enrolled, and 146 met all study eligibility criteria. In an intention to treat analysis where missing results were considered treatment failures, 59 patients (80%) assigned to moxifloxacin converted their 8-week sputum culture to negative vs. 45 (63%) of those assigned to ethambutol (p=0.03). Among patients with available cultures at Week 8, conversion rates were 92% (59/64) for moxifloxacin vs. 72% (45/61) for ethambutol (p=0.006). No differences in toxicity were observed. In a multivariate analysis, younger age (odds ratio 0.98, p=0.05), heavy baseline sputum smear positivity (OR 0.45, p <0.001) and treatment with moxifloxacin (OR 1.88, p<0.001) were significantly associated with sputum culture conversion. Moxifloxacin significantly improves culture conversion in the initial phase of tuberculosis treatment. Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis therapy are justified.