RT Journal Article
SR Electronic
T1 Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 322
OP 329
DO 10.1136/thoraxjnl-2012-202698
VO 68
IS 4
A1 Brusselle, Guy G
A1 VanderStichele, Christine
A1 Jordens, Paul
A1 Deman, René
A1 Slabbynck, Hans
A1 Ringoet, Veerle
A1 Verleden, Geert
A1 Demedts, Ingel K
A1 Verhamme, Katia
A1 Delporte, Anja
A1 Demeyere, Bénédicte
A1 Claeys, Geert
A1 Boelens, Jerina
A1 Padalko, Elizaveta
A1 Verschakelen, Johny
A1 Van Maele, Georges
A1 Deschepper, Ellen
A1 Joos, Guy F P
YR 2013
UL http://thorax.bmj.com/content/68/4/322.abstract
AB Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. ClinicalTrials.gov number NCT00760838.