A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment
A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment
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DOI：
10.1164/rccm.202102-0461oc
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发表时间：
2021-12-01
影响因子：
24.7
通讯作者：
Flume, Patrick A.
中科院分区：
文献类型：
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作者：
Goss, Christopher H.;Heltshe, Sonya L.;Flume, Patrick A.
理论基础：囊性纤维化(CF)患者的呼吸道症状和肺功能急剧恶化，称为肺恶化。静脉注射抗菌药物是一种常见的治疗方法，然而，几乎没有证据支持一个标准的治疗时间。目的：测试不同持续时间的静脉注射抗菌药物治疗慢性肺纤维化的疗效。方法：STOP2(肺加重标准化治疗2)是一项多中心、随机、对照的临床试验。在7-10天的治疗后，表现出预定的肺功能和症状改善的参与者被随机分为10天或14天的总抗菌时间；其余的随机分为14天或21天。测量和主要结果：主要结果是预测FEV1(ppFEV(1))从治疗开始到停药后2周的百分比。在早期应答者中，测试了10天到14天的非劣势；21天与14天相比，其他人的优势被比较。症状、体重和不良事件是次要的。在982名随机受试者中，277人符合改善标准，随机接受10天或14天的治疗；其余705人接受21天或14天的治疗。第10天和第14天的ppFEV(1)平均变化分别为12.8和13.4，差异-0.65(95%CI[-3.3至2.0])，不包括预先定义的非劣势边界。第21天和第14天的平均ppFEV1变化分别为3.3和3.4，相差-0.10(-1.3至1.1)。次级终点和敏感性分析得到支持。结论：在急性加重期早期治疗改善的成人CF患者中，静脉注射抗菌药物10天后的ppFEV(1)不低于14天。对于一周后改善较小的患者，21天并不比14天更好。
Rationale: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration.Objectives: To test differing durations of intravenous antimicrobials for CF exacerbations.Methods: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7-10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days' total antimicrobial duration; all others were randomized to 14 or 21 days' duration.Measurements and Main Results: The primary outcome was percent predicted FEV1 (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a -0.65 difference (95% CI [-3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV1 changes, a difference of -0.10 (-1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive.Conclusions: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days.