title: Azithromycin for Acute Exacerbations of Asthma : The AZALEA Randomized Clinical Trial.
abstract: Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use.
  
  
  
  To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit.
  
  
  
  The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids.
  
  
  
  Azithromycin 500 mg daily or matched placebo for 3 days.
  
  
  
  The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score.
  
  
  
  Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score.
  
  
  
  In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics.
  
  
  
  clinicaltrials.gov Identifier: NCT01444469.
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, England.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, England.
authors.forename: Matyas
authors.initials: M
authors.lastname: Szigeti
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, England.
authors.forename: Mary
authors.initials: M
authors.lastname: Cross
authors.affiliation: Institute for Lung Health, University of Leicester, Leicester, England.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brightling
authors.affiliation: Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, Scotland.|Respiratory Medicine, NHS Greater Glasgow and Clyde, Glasgow, Scotland.
authors.forename: Rekha
authors.initials: R
authors.lastname: Chaudhuri
authors.affiliation: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, England.
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
authors.affiliation: Respiratory Medicine, Heart of England Foundation Trust, Birmingham, England.|Severe and Brittle Asthma Unit, University of Birmingham, Birmingham, England.
authors.forename: Adel
authors.initials: A
authors.lastname: Mansur
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, England.
authors.forename: Laura
authors.initials: L
authors.lastname: Robison
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, England.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Sattar
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, England.
authors.forename: David
authors.initials: D
authors.lastname: Jackson
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, England.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, England.
authors.forename: Ernie
authors.initials: E
authors.lastname: Wong
authors.affiliation: Respiratory Medicine and Allergy, King's College London School of Medicine, London, England.|Department of Asthma, Allergy and Respiratory Science, Guy's and St. Thomas' NHS Foundation Trust, London, England.
authors.forename: Christopher
authors.initials: C
authors.lastname: Corrigan
authors.affiliation: Respiratory Medicine, Newcastle University, Newcastle, England.
authors.forename: Bernard
authors.initials: B
authors.lastname: Higgins
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, England.|Respiratory Medicine, Imperial College Healthcare NHS Trust, London, England.
authors.forename: Philip
authors.initials: P
authors.lastname: Ind
authors.affiliation: Centre for Respiratory Medicine and Allergy, Medicines Evaluation Unit, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, England.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, Scotland.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, England.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ashby
authors.affiliation: Respiratory Medicine, Portsmouth Hospitals NHS Trust, Portsmouth, England.
authors.forename: Anoop
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D017963:Azithromycin / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D004632:Emergency Medical Services; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin