Amoxycillin-clavulanate vs azithromycin for respiratory exacerbations of bronchiectasis in children: A multi-centre double blind non-inferiority RCT

Abstract

Introduction: Based on limited available data, amoxicillin-clavulanate is the current recommended first-line empirical oral-antibiotic treatment for non-severe bronchiectasis exacerbations in children. Azithromycin is an attractive alternative because of its long half-life, reduced dosing schedule, and good safety profile in children. We tested our primary hypothesis that oral azithromycin is non-inferior (within 20% margin) to amoxycillin-clavulanate at achieving resolution of exacerbation by day- 21 of treatment in children with bronchiectasis. Methods: We conducted a multicentre, parallel group, doubledummy, 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 (amoxycillinclavulanate 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.L6220917662018-05-16 <br />