LB01 - Intrapartum Oral Azithromycin to Prevent Maternal and Newborn Sepsis or Death: A Multinational RCT

Thursday, February 9, 2023

10:00 AM – 10:15 AM

Location: Moscone West, Level 3

Objective: 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.

Study Design: 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.

Results: 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).

Conclusion: 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.

Primary & Presenting Author(s)

Alan T. Tita, MD, PhD

Professor
University of Alabama at Birmingham
Birmingham, Alabama, United States

Slides

Coauthor(s)

WC

Waldemar Carlo, MD

Center for Women’s Reproductive Health and University of Alabama at Birmingham
Birmingham, Alabama, United States
Elizabeth M. McClure, PhD

Senior Research Epidemiologist
RTI International
Durham, North Carolina, United States