Goyal V, et al. - Whether azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis was investigated in this randomized controlled trial. In children with non-severe bronchiectasis, azithromycin showed non-inferiority for resolving exacerbations vs amoxicillin–clavulanate, as observed after 21 days of treatment. The risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of provoking macrolide resistance related to azithromycin treatment must be balanced against its benefits when treating some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, for whom azithromycin affords another option for treating exacerbations.

Methods

• Researchers conducted this parallel-group, double-dummy, double-blind, non-inferiority randomized controlled trial between April 2012 and August 2016 in three Australian and one New Zealand hospital.
• Children aged 1–19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis were enrolled.
• Oral suspensions of either amoxicillin–clavulanate (22.5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo were randomly administered for 21 days to children at the beginning of an exacerbation.
• Permuted block randomization (stratified by age, site, and cause) with concealed allocation was used.
• They focused on the resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%, as the primary outcome.
• Duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology were also evaluated as secondary outcomes.

Results

• A total of 604 children were screened and 236 were enrolled.
• An exacerbation was reported in 179 children, of those, 97 were treated with amoxicillin–clavulanate, 82 with azithromycin).
• Treatment for 21 days resulted in resolution of 61 (84%) of 73 exacerbations in the azithromycin group vs 73 (84%) of 87 in the amoxicillin–clavulanate group.
• Non-inferiority was demonstrated by the observed risk difference (-0.3%, 95% CI -11.8 to 11.1).
• In the amoxicillin–clavulanate group vs in the azithromycin group, significantly shorter exacerbations were reported (median 10 days [IQR 6–15] vs 14 days [8–16]; p=0.014).
• In the azithromycin group vs in the amoxicillin–clavulanate group, adverse events were attributed to the trial medication in 17 (21%) of 82 children vs 23 (24%) of 97, respectively (relative risk 0.9, 95% CI 0.5 to 1.5).