title: Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial.
abstract: BACKGROUND
  Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis.
  
  
  METHODS
  We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported.
  
  
  CONCLUSIONS
  Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel.
  
  
  BACKGROUND
  Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia. annechang@ausdoctors.net
authors.forename: Anne B
authors.initials: AB
authors.lastname: Chang
authors.forename: Keith
authors.initials: K
authors.lastname: Grimwood
authors.forename: Colin F
authors.initials: CF
authors.lastname: Robertson
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Wilson
authors.forename: Peter P
authors.initials: PP
authors.lastname: van Asperen
authors.forename: Kerry-Ann F
authors.initials: KA
authors.lastname: O'Grady
authors.forename: Theo P
authors.initials: TP
authors.lastname: Sloots
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Torzillo
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Bailey
authors.forename: Gabrielle B
authors.initials: GB
authors.lastname: McCallum
authors.forename: Ian B
authors.initials: IB
authors.lastname: Masters
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Byrnes
authors.forename: Mark D
authors.initials: MD
authors.lastname: Chatfield
authors.forename: Helen M
authors.initials: HM
authors.lastname: Buntain
authors.forename: Ian M
authors.initials: IM
authors.lastname: Mackay
authors.forename: Peter S
authors.initials: PS
authors.lastname: Morris
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001315:Australia; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D001987:Bronchiectasis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004311:Double-Blind Method; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009520:New Zealand; D011788:Quality of Life; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination; D017963:Azithromycin