Azithromycin Fails to Improve Preschool Wheeze in ED Trial

Key Takeaways

• Azithromycin was not associated with lower 5-day wheezing symptom scores than placebo.
• This pattern was observed in both the pathogenic-bacteria positive and pathogenic-bacteria negative cohorts.
• Bacterial clearance was higher with azithromycin in the positive cohort, while secondary outcomes, bacterial resistance, and adverse events appeared similar between groups.

In a multicenter randomized trial of 840 preschool children seen in the emergency department for moderate-to-severe wheezing, azithromycin did not lower wheezing-related symptom severity more than placebo over 5 days. The same pattern was seen in children who tested positive for pathogenic bacteria and those who did not. Children 18 to 59 months of age were assigned to azithromycin or matching placebo, and symptom severity was similar across groups.

The trial enrolled children 18 to 59 months of age who presented to the emergency department with a moderate-to-severe wheezing episode. Participants received azithromycin once daily at 12 mg per kilogram for 5 days or matching placebo. The prespecified primary endpoint was the 5-day sum of Asthma Flare-up Diary for Young Children scores, with higher scores indicating worse wheezing-related symptoms. Of the 840 randomized children, 521 tested positive for pathogenic bacteria, and the positive and negative cohorts were evaluated separately.

Primary symptom scores were similar between azithromycin and placebo in both cohorts. In the positive cohort, median ADYC scores were 9.59 with azithromycin and 9.72 with placebo, with interquartile ranges of 7.29 to 12.60 and 7.66 to 12.17, respectively; P=0.70. In the negative cohort, medians were 9.30 and 9.10, with interquartile ranges of 6.97 to 11.62 and 7.19 to 11.45, respectively; P=0.69. Overall, the symptom outcome was similar across treatment groups in both bacterial strata.

In the positive cohort, bacterial clearance was 58.7% with azithromycin and 11.4% with placebo at follow-up visits 1 to 3 weeks after randomization. Secondary outcomes were similar between groups, including emergency department length of stay, hospital length of stay, and return emergency department visits or hospitalizations within 72 hours. The development of bacterial resistance and the incidence of adverse events also appeared to be similar between groups.

The trial was stopped for futility after a planned interim analysis by the data and safety monitoring board. The report concluded that azithromycin did not lead to a greater reduction in wheezing-related symptom severity than placebo in preschool-age children with moderate-to-severe acute wheezing.