David M Haas1, Joanne Daggy2, Kathleen M Flannery3, Meredith L Dorr4, Carrie Bonsack4, Surya S Bhamidipalli2, Rebecca C Pierson5, Anthony Lathrop4, Rachel Towns3, Nicole Ngo6, Annette Head7, Sarah Morgan4, Sara K Quinney5. 1. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: dahaas@iupui.edu. 2. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana. 3. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana. 4. HealthNet, Indianapolis, Indiana. 5. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana. 6. Investigational Pharmacy, Eskenazi Health, Indianapolis, Indiana. 7. Investigational Pharmacy, IU Health, Indianapolis, Indiana.
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.
RCT Entities:
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.
Authors: William A Grobman; Madeline M Rice; Uma M Reddy; Alan T N Tita; Robert M Silver; Gail Mallett; Kim Hill; Elizabeth A Thom; Yasser Y El-Sayed; Annette Perez-Delboy; Dwight J Rouse; George R Saade; Kim A Boggess; Suneet P Chauhan; Jay D Iams; Edward K Chien; Brian M Casey; Ronald S Gibbs; Sindhu K Srinivas; Geeta K Swamy; Hyagriv N Simhan; George A Macones Journal: N Engl J Med Date: 2018-08-09 Impact factor: 91.245
Authors: Yana Vorontsova; David M Haas; Kathleen Flannery; Andrea R Masters; Larissa L Silva; Rebecca C Pierson; Brittany Yeley; Graham Hogg; David Guise; Michael Heathman; Sara K Quinney Journal: Clin Transl Sci Date: 2022-06-12 Impact factor: 4.438
Authors: Robbie S Kerr; Nimisha Kumar; Myfanwy J Williams; Anna Cuthbert; Nasreen Aflaifel; David M Haas; Andrew D Weeks Journal: Cochrane Database Syst Rev Date: 2021-06-22