Azithromycin to Reduce Mortality — An Adaptive Cluster-Randomized Trial

This large cluster-randomized trial (AVENIR) in Niger evaluated the mortality impact of twice-yearly azithromycin distributions to children. Communities were assigned to: (1) azithromycin for children 1–59 months, (2) azithromycin for infants 1–11 months plus placebo for older children, or (3) placebo for all. Across 382,586 children and 419,440 person-years of follow-up, treatment of all children significantly lowered mortality (11.9 vs. 13.9 deaths per 1000 person-years; 14% reduction; P<0.001). No statistically significant reduction was seen when only infants received azithromycin. Infant mortality was 17% lower when older children also received azithromycin, indicating a possible community-level protective effect. Only five serious adverse events occurred across groups. Findings support broader age eligibility for azithromycin distribution, though resistance surveillance remains essential

This large cluster-randomized trial (AVENIR) in Niger evaluated the mortality impact of twice-yearly azithromycin distributions to children. Communities were assigned to: (1) azithromycin for children 1–59 months, (2) azithromycin for infants 1–11 months plus placebo for older children, or (3) placebo for all. Across 382,586 children and 419,440 person-years of follow-up, treatment of all children significantly lowered mortality (11.9 vs. 13.9 deaths per 1000 person-years; 14% reduction; P<0.001). No statistically significant reduction was seen when only infants received azithromycin. Infant mortality was 17% lower when older children also received azithromycin, indicating a possible community-level protective effect. Only five serious adverse events occurred across groups. Findings support broader age eligibility for azithromycin distribution, though resistance surveillance remains essential