Vitality in Infants Via Azithromycin for Neonates Trial

Nearly half of child deaths occur during the neonatal period, and 80% of those occur in babies with low birthweight. Although tremendous progress has been made towards reducing under-five mortality globally, declines in neonatal mortality lag behind those observed in older children. Low birthweight babies are at increased risk of poor outcomes compared to those who are term-appropriate for gestational age, including mortality, stunting, and growth failure. Recent evidence has demonstrated that the incidence of wasting and linear growth failure is highest between birth and 3 months of age, substantially earlier than previously thought. Interventions are urgently needed to improve outcomes in low birthweight babies; however, these interventions must not interfere with breastfeeding and thus some well-established interventions used to treat or prevent malnutrition in older children cannot be considered. The investigators recently demonstrated that biannual mass azithromycin distribution reduces all-cause childhood mortality by approximately 25% in infants aged 1-5 months, with stronger effects seen in underweight infants. This study did not include neonates due to the risk of infantile hypertrophic pyloric stenosis (IHPS) that has been hypothesized to be associated with macrolide use during early infancy. However, our study team documented only a single case of IHPS among 21,833 neonates enrolled in a trial of azithromycin versus placebo administered to neonates aged 8-27 days for prevention of infant mortality, documenting no major risk of IHPS associated with azithromycin. Here, the investigators propose an individually randomized trial where participants will receive a single oral dose of azithromycin (administered either during the neontal period or 21 days after enrollment), two does of oral azithromycin spaced 21 days apart, or two doses of placebo to evalute if azithromycin improves nutritional outcome and reduces infectious burden among neonates aged 1-27 days who are either low birthweight (\<2500 g at birth) or underweight (weight-for-age Z-score \< -2 at enrollment). The primary outcome will be weight-for-age Z-score at 6 months of age compared between arms. The investigators anticipate that the results of this study will provide definitive evidence on azithromycin as an early intervention for low birthweight/underweight neonates, who are at the highest risk of adverse outcomes.

NCT Number	NCT05763693
Lead Sponsor	University of California, San Francisco Collaborators: Centre de Recherche en Sante de Nouna, Burkina Faso
Conditions	Neonatal Death, Infectious Disease, Nutritional Deficiency
Enrollment	4,000 participants
Start Date	2026-04
Primary Completion	2030-04 (estimated)
Study Completion	2030-04 (estimated)
Updated on ClinicalTrials.gov	2025-08-29