Methods: We conducted a multicentre, parallel group, double‐dummy, double‐blind placebo‐controlled RCT trial in 4 centres. At the start of an exacerbation, 179 children were randomised to receive either amoxycillin‐clavulanate (22.5 mg/kg bd)/placebo or azithromycin (5mg/kg/day)/placebo for 21‐days. Our primary outcome was resolution of exacerbation (defined as ‘return to baseline') by 21‐days. Study was powered for 90% (α=0.05, 1‐sided) with 20% non‐inferiority margin to detect 80% resolution rate by day‐21. Secondary outcomes were cough‐specific quality of life (PC‐QoL) and duration of exacerbation. Generalised linear model was used to calculate relative differences between groups.
Results: Baseline characteristics of the 2 groups (amoxycillin‐clavulanate n=97 and azithromycin n=82) were similar. By day‐21, resolution was comparable between groups, relative risk 0.99 95%CI 0.84‐1.17, falling within the a‐priori calculated 20% non‐inferiority margin. Between group differences for duration of exacerbation (2 days 95%CI ‐1.7, 5.3) and PC‐QoL at day‐21 compared to beginning of exacerbation was also within our non‐inferiority margin (0.42, 95%CI ‐0.06, 0.89).
Conclusion: Azithromycin is non‐inferior to amoxicillin‐clavulanate for treating non‐severe exacerbations of bronchiectasis in children. Azithromycin may be preferred to amoxicillin‐clavulanate in selected settings e.g. adherence. However, its use needs to be balanced with risk of treatment failure (within 20% compared to amoxicillin‐clavulanate) and inducing macrolide resistance.