Background

Biannual mass azithromycin administration reduces all-cause childhood mortality in some sub-Saharan African settings, with the largest effects in children aged 1-5 months. Azithromycin has not been distributed to children <1 month due to risk of infantile hypertrophic pyloric stenosis (IHPS).

Methods

This 1:1 placebo-controlled trial, randomized neonates aged 8-27 days to a single oral dose of azithromycin (20 mg/kg) or equivalent volume of placebo in 5 regions of Burkina Faso during 2019 and 2020. The primary outcome was all-cause mortality at 6 months of age. Infants were evaluated at 21 days after treatment and at 3 and 6 months of age for vital status; family and provider surveillance for IHPS continued throughout.

Results

Of 21,832 enrolled neonates, 10,898 were allocated to azithromycin and 10,934 to placebo. At 6 months of age, 92 infants had died, 42 (0.44%) in the azithromycin group and 50 (0.52%) in the placebo group (hazard ratio 0.85, 95% confidence interval 0.56 to 1.28, P=0.46). A single IHPS case was detected, which was in the azithromycin arm. Serious adverse events, including death and hospitalization within 28 days of treatment, occurred in 0.27% of infants in the azithromycin group and 0.14% in the placebo group, for an absolute risk difference 0.14 percentage points, 95% confidence interval 0.01 to 0.26.

Conclusions

Overall mortality was lower than anticipated when the trial was designed, thus limiting its power. The available data do not support the routine use of azithromycin for prevention of mortality in neonates in sub-Saharan African settings similar to the one in which this trial was conducted.

Trial registration

ClinicalTrials.gov NCT03682653.