Division of Pulmonary, Critical Care and Sleep Medicine, University of Buffalo, State University of New York, Buffalo, NY, USA.
Respir Res. 2010 Jan 28;11(1):10. doi: 10.1186/1465-9921-11-10.
Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.
Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.
At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).
Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development.
ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).
急性加重是导致慢性阻塞性肺疾病（COPD）相关发病率和死亡率的原因。这项概念验证研究评估了间歇性脉冲莫西沙星治疗是否可以降低这些加重的频率。
稳定期 COPD 患者随机进行双盲、安慰剂对照试验，接受莫西沙星 400mg PO 每日一次（N=573）或安慰剂（N=584）每日一次，共 5 天。每 8 周重复治疗，共进行 6 个疗程。在 48 周的治疗期间和进一步的 24 周随访中，患者反复进行临床和微生物学评估。
48 周时，发生加重的优势比（OR）有利于莫西沙星：方案人群（N=738，OR0.75，95%置信区间（CI）0.565-0.994，p=0.046），意向治疗（ITT）人群（N=1149，OR0.81，95%CI0.645-1.008，p=0.059），以及基线时产生脓性/粘液脓性痰的方案人群（PP）患者的事后分析（N=323，OR0.55，95%CI0.36-0.84，p=0.006）。在任何预先指定的疗效亚组分析或住院率、死亡率、肺功能或圣乔治呼吸问卷（SGRQ）总分的变化方面，莫西沙星与安慰剂之间均无显著差异。然而，在 SGRQ 症状领域，莫西沙星有显著优势（ITT：-8.2 与-3.8，p=0.009；PP：-8.8 与-4.4，p=0.006）。莫西沙星治疗与莫西沙星敏感性的持续变化无关。莫西沙星治疗组比安慰剂组出现更多的治疗相关不良事件（p<0.001），主要是胃肠道事件（4.7%与 0.7%）。
在 ITT 人群中，间歇性脉冲莫西沙星治疗使加重的几率降低了 20%，在 PP 人群中降低了 25%，在基线时产生脓性/粘液脓性痰的 PP 患者中降低了 45%。没有出现意外的不良事件，也没有证据表明耐药性的发展。
ClinicalTrials.gov 编号，NCT00473460（ClinicalTrials.gov）。
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