Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial
- Guy G Brusselle1,
- Christine VanderStichele1,
- Paul Jordens2,
- René Deman3,
- Hans Slabbynck4,
- Veerle Ringoet5,
- Geert Verleden6,
- Ingel K Demedts7,
- Katia Verhamme8,
- Anja Delporte1,
- Bénédicte Demeyere1,
- Geert Claeys9,
- Jerina Boelens9,
- Elizaveta Padalko9,
- Johny Verschakelen10,
- Georges Van Maele11,
- Ellen Deschepper11,
- Guy F P Joos1
- 1Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
- 2Department of Respiratory Medicine, OLV Ziekenhuis, Aalst, Belgium
- 3Department of Respiratory Medicine, AZ Groeninge, Kortrijk, Belgium
- 4Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium
- 5Department of Respiratory Medicine, AZ Sint-Jan, Brugge, Belgium
- 6Department of Respiratory Medicine, University Hospital Gasthuisberg, Leuven, Belgium
- 7Department of Respiratory Medicine, Heilig Hart Ziekenhuis, Roeselare, Belgium
- 8Department of Epidemiology, Erasmus MC Rotterdam, Rotterdam, The Netherlands
- 9Department of Microbiology, Clinical Chemistry and Immunology, Ghent University Hospital, Ghent, Belgium
- 10Department of Radiology, University Hospital Gasthuisberg, Leuven, Belgium
- 11Biostatistics Unit, Department of Public Health, Ghent University Hospital, Ghent, Belgium
- Correspondence to Dr Guy G Brusselle, Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, Ghent B-9000, Belgium;
- Received 7 September 2012
- Revised 13 November 2012
- Accepted 26 November 2012
- Published Online First 3 January 2013
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.