Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.
BACKGROUND
Azithromycin is a macrolide antibiotic with anti-inflammatory 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 fibrosis 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 defined by high-resolution 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 stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV(1)) 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.


RESULTS
71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26-0·54; p<0·0001). Prebronchodilator FEV(1) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI -0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (-5·17 units) and placebo groups (-1·92 units; difference -3·25, 95% CI -7·21 to 0·72; p=0·108).


CONCLUSIONS
Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year.


BACKGROUND
Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.
Department of Respiratory Medicine, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand. cawong@middlemore.co.nz
Conroy
C
Wong
Lata
L
Jayaram
Noel
N
Karalus
Tam
T
Eaton
Cecilia
C
Tong
Hans
H
Hockey
David
D
Milne
Wendy
W
Fergusson
Christine
C
Tuffery
Paul
P
Sexton
Louanne
L
Storey
Toni
T
Ashton
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001987:Bronchiectasis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003550:Cystic Fibrosis / Q000150:complications; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D055502:Secondary Prevention; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D000900:Anti-Bacterial Agents; D017963:Azithromycin