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 misoprostol dosing for efficacy, safety, and patient satisfaction is important and not well studied for the buccal route.

Objective: To compare the efficacy and safety of vaginal and buccal misoprostol for women undergoing labor induction at term.

Study design: The IMPROVE trial was an institutional review board-approved, triple-masked, placebo-controlled randomized noninferiority trial for women undergoing labor induction at term with a Bishop score ≤6. Enrolled women received 25 mcg (first dose), then 50 mcg (subsequent doses) of misoprostol by assigned route (vaginal or buccal) and a matching placebo tablet by the opposite route. The primary outcomes were time to delivery and the rate of cesarean delivery performed urgently for fetal nonreassurance. A sample size of 300 was planned to test the noninferiority hypothesis.

Results: The trial enrolled 319 women, with 300 available for analysis, 152 in the vaginal misoprostol group and 148 in the buccal. Groups had similar baseline characteristics. We were unable to demonstrate noninferiority. The time to vaginal delivery was lower for the vaginal misoprostol group (median [95% confidence interval] in hours: vaginal: 20.1 [18.2, 22.8] vs buccal: 28.1 [24.1, 31.4], log-rank test P = .006, Pnoninferiority = .663). The rate of cesarean deliveries for nonreassuring fetal status was 3.3% for the vaginal misoprostol group and 9.5% for the buccal misoprostol group (P = .033). The rate of vaginal delivery in <24 hours was higher in the vaginal group (58.6% vs 39.2%, P = .001).

Conclusion: We were unable to demonstrate noninferiority. In leading to a higher rate of vaginal deliveries, more rapid vaginal delivery, and fewer cesareans for fetal issues, vaginal misoprostol may be superior to buccal misoprostol for cervical ripening at term.

Trial registration: ClinicalTrials.gov NCT02408315.

Keywords: Buccal; cervical ripening; labor induction; misoprostol; term pregnancy; vaginal.

Conflict of interest statement

The authors declare no conflict of interest with the content of this manuscript. There was no funding source for this work other than internal Department funds for resident research. Dr Pierson’s time as an OB-Clinical Pharmacology was supported by NIH-NIGMS: Indiana University Comprehensive Training in Clinical Pharmacology (T32GM008425).

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

FIGURE 1

CONSORT diagram of participant flow through IMPROVE trial

FIGURE 2. Kaplan-Meier curves illustrating time to delivery

Top panel shows time to delivery from start of induction (in hours) for all women in IMPROVE trial, stratified by route of misoprostol. Bottom panel shows time to delivery for participants stratified by nulliparous (yes or no) and route of misoprostol. Women delivered by cesarean delivery are censored at the time of that delivery. Numbers below the graphs are the number of women in each group still pregnant at that time point. BM, buccal misoprostol; VM, vaginal misoprostol.