Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials
Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials
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DOI：
10.1016/s2213-2600(14)70165-1
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发表时间：
2014-09-01
影响因子：
76.2
通讯作者：
O'Riordan, Thomas G.
中科院分区：
文献类型：
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作者：
Barker, Alan F.;O'Donnell, Anne E.;O'Riordan, Thomas G.
背景：吸入抗生素治疗非囊性纤维化支气管扩张的临床获益尚未在随机对照试验中得到证实。我们的目的是评估aztreonam吸入溶液（AZLI）在非囊性纤维化支气管扩张和革兰氏阴性细菌定植患者中的安全性和有效性。方法AIR-BX1和AIR-BX2是两项双盲、多中心、随机、安慰剂对照的3期试验，纳入18岁及以上支气管扩张、痰液或靶革兰氏阴性菌支气管镜培养阳性的患者。患者被随机分配接受AZLI或安慰剂（1:1）。随机化在没有分层的情况下进行，代码由吉利德指定人员生成。在这两项研究中，AZLI 75 mg或安慰剂（每日三次；eFlow雾化器）的两个为期4周的疗程后，每个疗程均为4周的停药期。主要终点是4周时支气管扩张呼吸症状评分（QOL-B-RS S）较基线生活质量的变化。这些试验已在ClinicalTrials.gov注册，编号为AIRBX1的NCT01313624和AIR-BX2的NCT01314716。研究结果：我们从47家AIR-BX1门诊诊所和65家AIR-BX2门诊诊所招募参与者；研究是在2011年4月25日至2013年7月1日之间完成的。在AIR-BX1中，筛选的348例患者中，134例随机分配接受AZLI治疗，132例接受安慰剂治疗。在AIR-BX2中，筛选的404例患者中，136例随机分配接受AZLI治疗，138例接受安慰剂治疗。在4周时，AZLI和安慰剂从基线QOL-B-RS调整后的平均变化差异无统计学意义（0.8 [95% CI 3.1至4]）。7], p = 0。68)，但差异有统计学意义(4。[1.] [1.][2], p= 0.011)。AIR-BX2 4周后QOL-B-RSS 4.6分的差异不认为具有临床意义。在这两项研究中，与治疗相关的不良事件在AZLI组中比在安慰剂组中更常见，不良事件的中断也是如此。最常见的治疗不良事件是呼吸困难、咳嗽和痰增多。这两种情况在阿兹利治疗组比安慰剂治疗组更常见，但在AIR-BX2组发病率更为平衡。根据QOL-B-RSS测量，AZLI治疗对非囊性纤维化支气管扩张没有显著的临床益处，这表明仍需要安慰剂对照研究来确定吸入抗生素对该疾病患者的临床益处。
Background The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation.Methods AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RS S) at 4 weeks. These trials are registered with ClinicalTrials.gov, numbers are NCT01313624 for AIRBX1 and NCT01314716 for AIR-BX2.Findings We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RS S was not significant at 4 weeks (0.8 [95% CI 3.1 to 4. 7], p=0. 68) in AIRBX1, but was significant (4. 6 [1.1 to 8. 2], p=0 011) in AIR-BX2. The 4.6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2.Interpretation AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder.