A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation

Thorax. 2015 May;70(5):442-50. doi: 10.1136/thoraxjnl-2014-205998. Epub 2015 Feb 24.


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.

Outcome: 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who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV1 at 12 weeks.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.

Trial registration number: EU-CTR, 2006-000485-36/GB.

Keywords: Lung Transplantation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / therapeutic use*
  • Bronchiolitis Obliterans / diagnosis
  • Bronchiolitis Obliterans / drug therapy*
  • Bronchiolitis Obliterans / etiology
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Syndrome
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Azithromycin