A comparison of vaginal versus buccal misoprostol for cervical ripening in women for labor induction at term (the IMPROVE trial): a triple masked randomized controlled trial

Abstract Background Cervical ripening is commonly needed for labor induction. Finding an optimal route of misoprostoldosing for efficacy, safety, and patient satisfaction is important and not well studied for the buccal route. Objective To compare the efficacy and safety of vaginaland buccal misoprostolfor women undergoing labor inductionat term. Study Design The IMPROVE trial was an IRB-approved, triple-masked, placebo-controlled randomized non-inferiority trial for women undergoing labor inductionat term with a Bishop’s Score ≤ 6. Enrolled women received 25 mcg (1 st dose), then 50 mcg (subsequent doses) of misoprostolby assigned route ( vaginal[VM] or buccal [BM]) and a matching placebo tablet by the opposite route. The primary outcomes were time to delivery and the rate of cesarean delivery performedurgently for fetal non-reassurance. A sample size of 300 was planned to test the non-inferiority hypothesis. Results The trial enrolled 319 women, with 300 available for analysis, 152 VM and 148 BM. Groups had similar baseline characteristics. We were unable to demonstrate non-inferiority. The time to vaginal deliverywas lower for the VM group (median [95% confidence interval] in hours: VM: 20.1 [18.2, 22.8] vs. BM: 28.1 [24.1, 31.4], Log-rank test p=0.006, p non-inferiority = 0.663). The rate of cesarean deliveries for non-reassuring fetal status was 3.3% for the VM group and 9.5% for the BM group (p=0.033). The rate of vaginal deliveryin Conclusion We were unable to demonstrate non-inferiority. In leading to a higher rate of vaginal deliveries, more rapid vaginal delivery, and fewer cesareans for fetal issues, vaginal misoprostolmay be superior to buccal misoprostolfor cervical ripening at term.