Azithromycin to improve latency in examination-indicated cerclage: a multicenter randomized controlled trial

Physical examination-indicated cerclage is an intervention offered to prolong pregnancy in the setting of painless cervical dilation before 24 weeks of gestation. Of note, 1 randomized clinical trial showed an increased incidence of pregnancy prolongation by at least 28 days among participants who received perioperative indomethacin and cefazolin in the setting of a physical examination-indicated cerclage compared with those who did not receive those perioperative medications. Prospective studies have suggested that prophylactic azithromycin may increase latency in the setting of cervical shortening. However, this has not been studied in a controlled manner in patients undergoing physical examination-indicated cerclage.

This study aimed to determine whether the addition of perioperative azithromycin to cefazolin and indomethacin for physical examination-indicated cerclage increases the latency to delivery compared with perioperative cefazolin and indomethacin alone.

This was an open-label multicenter randomized controlled trial of individuals with singleton gestations who were undergoing a physical examination-indicated cerclage between December 2021 and September 2023 at 4 sites across the United States. This study was approved by the institutional review board and was registered on ClinicalTrials.gov (registration number: NCT05132829). Participants were randomized 1:1 via a computer-generated randomization sequence stratified by site to standard of care (cefazolin 1-2 g intravenously and indomethacin 50 mg preoperatively followed by 2 additional doses at 8 and 16 hours postoperatively, control arm) or standard of care plus azithromycin (azithromycin 1000 mg intravenously in addition to cefazolin and indomethacin described in the control group, azithromycin arm). The primary outcome was gestational latency (days) from cerclage placement to delivery. The secondary outcomes included preterm birth, gestational age at delivery, chorioamnionitis, and neonatal morbidity and mortality.

A total of 82 pregnant individuals were assessed for eligibility, and 54 participants were randomized, 27 to the control arm and 27 to the azithromycin arm. In the primary intention-to-treat analysis, the median gestational latency from cerclage placement to delivery did not differ between the intervention and control groups (92 days [interquartile range, 45-118] vs 85 [interquartile range, 20-123] days, respectively; P=.93). Furthermore, there was no statistically significant difference found in any of the secondary obstetrical or neonatal outcomes.

A single perioperative dose of azithromycin in addition to standard of care cefazolin and indomethacin does not improve the latency to delivery or other perinatal outcomes compared with standard of care alone in patients with singleton gestations undergoing a physical examination-indicated cerclage.