Intrapartum oral azithromycin to prevent maternal and newborn sepsis or death: a multinational rct

Abstract

Sepsis is among the top causes of maternal and newborn death worldwide. Based on promising data from 2 small trials, we tested the hypothesis that a single oral dose of azithromycin (AZI) given during labor in women planning a vaginal delivery would reduce maternal death or perinatal death or sepsis. Women in labor at ≥28 weeks’ gestation with a live fetus and planned vaginal delivery were randomized to either a single oral dose of 2g AZI or identical placebo at 8 sites in 7 low- and middle-income countries (LMICs). There were 2 primary outcomes: 1) a composite of maternal death or sepsis and 2) a composite of stillbirth or neonatal death or sepsis. Secondary outcomes included specific maternal infections, hospital readmission and unscheduled healthcare visits. A sample size of N=34,000 would provide up to 90% power to detect 20% reduction in each primary composite outcome assuming 2-sided alpha = 0.05, loss to follow-up = 2-3% and baseline rates of 3% (maternal outcome) and 6% (newborn outcome). During an interim analysis ( >70%), the Data Monitoring Committee recommended to stop the trial for benefit. A total of 29,278 participants were randomized; 14590 to AZI and 14688 to placebo and 99.6% followed to 42 days postpartum. Baseline characteristics were remarkably well-balanced between groups including overall from Africa (40%), Asia (55%) and Latin America (5%), nulliparous (43%), labor induction (18%) and high-risk i.e. labor ≥24 hours or membrane rupture ≥8 hours prior to randomization (8.6%). The maternal primary outcome (1.6% vs. 2.4%) and sepsis (1.5% vs. 2.3%) risks were lower in the AZI group; p-values < 0.005 (Table). The risks of maternal endometritis, wound infections, other infections, readmissions and unscheduled visits were also lower with AZI (Table). The risk of the newborn primary outcome (10.5% vs. 10.3%) did not differ by group (p=0.54). A single intrapartum oral dose of AZI reduced the risk of maternal death or sepsis, but not newborn death or sepsis in women in labor planning to deliver vaginally.