Vaginal Compared with Oral Misoprostol Induction at Term: A Cluster Randomized Controlled Trial

OBJECTIVE:To evaluate efficacy in achieving vaginal delivery with a standardized vaginal compared with oral misoprostol regimen for labor induction at term.METHODS:In this single-center, cluster randomized trial, we randomized induction method by week among individuals with gestational age of 37 weeks or more, cervical dilation of 2 cm or less, intact membranes, and indication for delivery to either oral (100 micrograms every 4 hours for up to two doses), or vaginal (25 micrograms every 3 hours for up to five doses) misoprostol regimens, followed by a standardized oxytocin protocol. Individuals with an antepartum stillbirth, major fetal anomalies, malpresentation, ruptured membranes, nonreassuring fetal status, or contraindication to prostaglandin were excluded. The primary outcome was vaginal delivery at first induction attempt. Secondary outcomes included time to delivery, need for oxytocin, chorioamnionitis, and adverse maternal and neonatal outcomes. Outcomes were recorded at the individual level and adjusted for clustering, with analysis by intention to treat.RESULTS:Between May 24, 2021, to September 19, 2022, 1,322 women were randomized to vaginal misoprostol in 33 clusters and 1,224 to oral misoprostol in 37 clusters. Demographic characteristics or initial cervical dilation did not differ between groups. The primary outcome did not differ between induction regimens and occurred in 1,032 (78.1%) of the vaginal misoprostol arm and 945 (77.2%) of the oral misoprostol arm (adjusted relative risk [RR] 1.01, 95% CI, 0.97-1.05). Tachysystole with fetal heart rate changes occurred less frequently with vaginal compared with oral misoprostol (3.5% vs 5.9%, adjusted RR 0.59, 95% CI, 0.40-0.87). Time to delivery did not differ between groups. Oxytocin was less frequently required before delivery in the vaginal misoprostol group (68.8% vs 78.4%, adjusted RR 0.88, 95% CI, 0.84-0.92).CONCLUSION:Induction of labor with vaginal compared with oral misoprostol protocols did not increase the frequency of vaginal delivery at term but did reduce the need for oxytocin use before delivery.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT04755218.