Azithromycin for prevention of exacerbations in non-cystic fi brosis bronchiectasis (EMBRACE): A randomised, double-blind, placebo-controlled trial.

Abstract

Background Azithromycin is a macrolide antibiotic with anti-infl ammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fi brosis bronchiectasis. Methods We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defi ned by highresolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratifi ed by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of eventbased exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV1) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493. Findings 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 059 per patient in the azithromycin group and 157 per patient in the placebo group in the 6-month treatment period (rate ratio 038, 95% CI 026-054; p<00001). Prebronchodilator FEV1 did not change from baseline in the azithromycin group and decreased by 004 L in the placebo group, but the diff erence was not signifi cant (004 L, 95% CI -003 to 012; p=0251). Additionally, change in SGRQ total score did not diff er between the azithromycin (-517 units) and placebo groups (-192 units; diff erence -325, 95% CI -721 to 072; p=0108). Interpretation Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fi brosis bronchiectasis with a history of at least one exacerbation in the past year. Funding Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.