A single oral dose of azithromycin was found to significantly lower the risk of maternal sepsis or death among women planning a vaginal delivery, according to new data published in The New England Journal of Medicine.
The National Institutes of Health (NIH)-led phase 3 study (A-PLUS; ClinicalTrials.gov Identifier: NCT03871491) included 29,278 women who were in labor at 28 weeks’ gestation or more and who were planning a vaginal delivery. Between September 2020 and August 2022, study participants were randomly assigned to receive either a single 2g oral dose of azithromycin or placebo during labor. The primary endpoints of the study were the incidence of maternal death or sepsis, as well as the incidence of intrapartum/neonatal death or sepsis.
Within the first 6 weeks after delivery, the incidence of maternal sepsis or death was 1.6% in the azithromycin arm compared with 2.4% in the placebo arm, with a relative risk of 0.67 (95% CI, 0.56-0.79; P <.001). Findings showed the maternal primary outcome was mainly driven by the difference in the incidence of sepsis between the azithromycin and placebo arms (1.5% vs 2.3%, respectively), with a relative risk of 0.65 (95% CI, 0.55-0.77).
While treatment with azithromycin significantly lowered the risk of maternal sepsis or death compared with placebo, the analysis demonstrated little effect on neonatal death or sepsis (10.5% vs 10.3%), with a relative risk of 1.02 (95% CI, 0.95-1.09; P =.56).
The study was originally designed to enroll up to 34,000 women. However, during an interim analysis, the trial was stopped early due to the clear maternal benefit based on a recommendation from the data and safety monitoring committee.
“These findings have the potential to change clinical practice by providing a safe, effective and low-cost approach to reduce the global burden of maternal sepsis and death,” said Diana W. Bianchi, MD, director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the primary funder of the trial. “We urgently need effective strategies to prevent pregnancy-related infections, which account for roughly 10% of maternal deaths worldwide.”
- Single-dose antibiotic prevents maternal sepsis and death. News release. National Institutes of Health. Accessed February 9, 2023. https://www.nih.gov/news-events/news-releases/single-dose-antibiotic-prevents-maternal-sepsis-death.
- Tita AT, Carlo WA, McClure EM, et al. Azithromycin to prevent sepsis or death in women planning a vaginal birth. N Engl J Med. Published online February 9, 2023. doi:10.1056/NEJMoa2212111
This article originally appeared on MPR