93: Induction of labor at term with a live fetus: is 25μg of vaginal misoprostol non inferior to slow release 10mg PGE2 Pessary? CYTOPRO, A french multicentre randomized controlled trial, (NCT01765881)

Abstract

To test whether 25μg vaginal misoprostol is non-inferior to slow release PGE2 pessary for induction of labor with unfavorable cervix at term. This is an open-label multicenter randomized controlled trial conducted in 4 hospitals of the Research Group in Obstetrics and Gynecology (GROG). We included women necessitating induction of labor with an unfavorable cervix at term (≥ 36 weeks) with a singleton pregnancy in cephalic presentation without prior cesarean section (CS). Women were randomly allocated to 25μg vaginal misoprostol 4-hourly or PGE2 pessary. Primary outcome was total CS rate. Secondary outcome was drug tolerance. Analyses were done both by intention-to-treat and per protocol. In this non-inferiority trial, the non-inferiority margin was 5% of the absolute difference in the CS rate. We randomized 836 women to vaginal misoprostol and 838 women to PGE2 pessary between September 2013 and June 2015. Total CS rate was 22.0% in the misoprostol and 19.8% in the PGE2 groups. The absolute difference in CS rates between misoprostol and PGE2 groups was 2.2% with an upper 95% confidence limit of 5.5% that exceeded the non-inferiority margin (5%) in the intention-to treat and per protocol analysis sets. Rate of deliveries ≤ 24 hours was significantly higher in the misoprostol group (72.9% vs. 55.9%; p< 0.001). Neonatal morbidity was comparable between groups in terms of arterial umbilical cord pH < 7.05 (1.3% vs. 1.6%, p=0.6), 5-minute Apgar score < 7 (3.6% vs. 4.8.5%, p=0.2) and meconium-stained amniotic fluid (4.2% vs. 3.9%, p=0.8). Rates of uterine hyperstimulation with and without FHR changes were not different between groups. Non-inferiority of 25μg vaginal misoprostol 4-hourly to PEG2 pessary on CS rate for induction of labor at term was not demonstrated in our multicenter RCT. However, as neonatal morbidity was comparable and CS rates very close, both drugs could be considered.