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

作者：Barker Alan F^*; O' Donnell Anne E; Flume Patrick; Thompson Philip J; Ruzi Jonathan D; de Gracia Javier; Boersma Wim G; De Soyza Anthony; Shao Lixin; Zhang Jenny; Haas Laura; Lewis Sandra A; Leitzinger Sheila; Montgomery A Bruce; McKevitt Matthew T; Gossage David; Quittner Alexandra L; O' Riordan Thomas G

来源：Lancet Respiratory Medicine, 2014, 2(9): 738-749.

DOI：10.1016/S2213-2600(14)70165-1

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2014-9