Primary Objective 1A:

To assess the efficacy of maternal azithromycin delivered twice antenatally (2nd/3rd trimesters) and intra/peripartum (three total doses) to reduce a composite outcome of stillbirths and infant mortality through 6–12 months of age.

Primary Objective 1B:

To assess the efficacy of infant azithromycin delivered at the first and third doses of routine pentavalent vaccine (~6 and 14 weeks of age) to reduce infant mortality from the time of first dose through 6–12 months of age.

Enrol target sample size:

Mother-infant cohort = 49,600

Infant-only cohort = 10,000 between Q3 2020 and Q1 2023

Completion of follow-up: between Q2 2023 and Q1 2024

Data cleaning/analysis: between Q2 and Q4 2024

Results readout expected: October 2024

2×2 factorial design

• Pregnant women receive up to three single 2g doses of azithromycin or placebo (two antenatal + one intra / peripartum)

• Infants receive two single 20mg/kg doses of azithromycin or placebo

Study specificities

Other studies are assessing maternal or infant azithromycin – SANTÉ is testing both.

In SANTÉ, infants are dosed indirectly via peripartum dose and twice within the first 4 months of life (at 6 and 14 weeks). Coverage during highest-risk period. SANTÉ is testing an intervention delivered through the routine antenatal care and immunization platforms. Scale-up uses existing infrastructure.

81 health facilities in rural Mali, in the Sikasso region, south-east, based in three main districts: Koutiala, Kignan, Niéna.

Ancillary SANTÉ studies will assess the impact of maternal / infant azithromycin on the following:

• Antimicrobial resistance (phenotypic and genomic markers of resistance)

• Maternal and infant malaria/prospective data collection on SMC/IPTp
• Biomarkers of environmental enteric dysfunction
• The vaginal and gut (maternal/infant) microbiome
• Immune response to rotavirus vaccination
• Seroprevalence and sero-response to common pathogens
• Impact on infant growth (anthropometric measurements).