Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial
Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(17)31281-3
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发表时间：
2017-08-12
期刊：
影响因子：
168.9
通讯作者：
Simpson, Jodie L.
中科院分区：
文献类型：
--
作者：
Gibson, Peter G.;Yang, Ian A.;Simpson, Jodie L.
背景：哮喘急性发作造成了巨大的全球疾病负担。尽管维持治疗，但持续性哮喘不受控制的成人需要额外的治疗。由于大环内酯类抗生素可用于治疗持续性哮喘，我们的目的是评估口服阿奇霉素作为添加治疗在中等至高剂量吸入性皮质类固醇加长效支气管扩张剂的不受控制的持续性哮喘患者的有效性和安全性。安慰剂对照平行组试验，以确定口服阿奇霉素是否降低成人哮喘急性发作的频率（≥ 18岁）患有症状性哮喘，尽管目前使用吸入性皮质类固醇和长效支气管扩张剂，并且没有听力损害或校正的QT间期异常延长。患者被随机分配（1：1）接受阿奇霉素500 mg或安慰剂，每周3次，共48周。使用计算机生成的随机数字表中的隐藏随机分配对患者进行集中分配，其中排列区组为4或6，并对中心和既往吸烟进行分层。主要疗效终点为48周内总（重度和中度）哮喘急性发作率和哮喘生活质量。结果在2009年6月12日至2015年1月31日期间，420名患者被随机分配（阿奇霉素组213名，安慰剂组207名）。与安慰剂组（1.86/患者年[1.54-2.18];发病率比[IRR] 0.59 [95%CI 0.47-0.74]; p
Background Exacerbations of asthma cause a substantial global illness burden. Adults with uncontrolled persistent asthma despite maintenance treatment require additional therapy. Since macrolide antibiotics can be used to treat persistent asthma, we aimed to assess the efficacy and safety of oral azithromycin as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high dose inhaled corticosteroids plus a long-acting bronchodilator.Methods We did a randomised, double-blind, placebo controlled parallel group trial to determine whether oral azithromycin decreases the frequency of asthma exacerbations in adults (>= 18 years) with symptomatic asthma despite current use of inhaled corticosteroid and long-acting bronchodilator, and who had no hearing impairment or abnormal prolongation of the corrected QT interval. Patients were randomly assigned (1: 1) to receive azithromycin 500 mg or placebo three times per week for 48 weeks. Patients were centrally allocated using concealed random allocation from a computer-generated random numbers table with permuted blocks of 4 or 6 and stratification for centre and past smoking. Primary efficacy endpoints were the rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma quality of life. Data were analysed on an intention-to-treat basis.Findings Between June 12, 2009, and Jan 31, 2015, 420 patients were randomly assigned (213 in the azithromycin group and 207 in the placebo group). Azithromycin reduced asthma exacerbations (1.07 per patient-year [95% CI 0.85-1.29]) compared with placebo (1.86 per patient-year [1.54-2.18]; incidence rate ratio [IRR] 0.59 [95% CI 0.47-0.74]; p