Vitality in Infants Via Azithromycin for Neonates Trial (VIVANT)

/ABSTRACT 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 and those who are underweight and wasted (collectively referred to as infants at risk of poor growth and development); 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. We 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. Recently, our study team documented only a single case of IHPS among 21,832 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, we propose an individually randomized trial to test whether oral azithromycin improves nutritional outcomes and reduces infectious burden among neonates aged 1-27 days who are at risk of poor growth and development. The primary outcome will be weight-for-age Z-score at 6 months of age compared between arms. We anticipate that the results of this study will provide definitive evidence on azithromycin as an early intervention for neonates at risk of poor growth and development, who are at the highest risk of adverse outcomes. Project Number: 1R01HD114864-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Catherine Oldenburg | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $450,170 | Activity Code: R01 | Study Section: Reproductive, Perinatal and Pediatric Health Study Section[RPPH] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HD11486401A1