title: A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation.
abstract: BACKGROUND
  We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation.
  
  
  METHODS
  We compared azithromycin (250 mg alternate days, 12 weeks) with placebo. Primary outcome was FEV1 change at 12 weeks.
  
  
  RESULTS
  48 patients were randomised; (25 azithromycin, 23 placebo). It was established, post randomisation that two did not have BOS. 46 patients were analysed as intention to treat (ITT) with 33 'Completers'. ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal.
  
  
  RESULTS
  The ITT analysis (n=46, 177 observations) estimated mean difference in FEV1 between treatments (azithromycin minus placebo) was 0.035 L, with a 95% CI of -0.112 L to 0.182 L (p=0.6). Five withdrawals, who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV1 at 12 weeks. Study Completers showed an estimated mean difference in FEV1 between treatment groups (azithromycin minus placebo) of 0.278 L, with 95% CI for the mean difference: 0.170 L to 0.386 L (p=<0.001). Nine of 23 ITT patients in the azithromycin group had ≥10% gain in FEV1 from baseline. No patients in the placebo group had ≥10% gain in FEV1 from baseline while on placebo (p=0.002). Seven serious adverse events, three azithromycin, four in the placebo group, were deemed unrelated to study medication.
  
  
  CONCLUSIONS
  Azithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo. This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS.
  
  
  BACKGROUND
  EU-CTR, 2006-000485-36/GB.
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK Institute of Cellular Medicine, Newcastle upon Tyne, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Corris
authors.affiliation: Institute of Health and Society Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ryan
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Therese
authors.initials: T
authors.lastname: Small
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: James
authors.initials: J
authors.lastname: Lordan
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK Institute of Cellular Medicine, Newcastle upon Tyne, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fisher
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Gerard
authors.initials: G
authors.lastname: Meachery
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Johnson
authors.affiliation: Institute of Cellular Medicine, Newcastle upon Tyne, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Ward
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin
keywords: Lung Transplantation