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 FEV 1 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 FEV 1 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who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV 1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV 1 at 12 weeks. Study Completers showed an estimated mean difference in FEV 1 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 FEV 1 from baseline. No patients in the placebo group had ≥10% gain in FEV 1 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 FEV 1 in patients with BOS and appears superior to placebo. This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS.