Misoprostol Reduces Median Time to Delivery by Several Hours

July 16, 2013

A 200-μg, controlled-release misoprostol vaginal insert reduced median time to vaginal delivery by 11.3 hours compared with another prostaglandin, but it also increased the rate of uterine tachysystole, according to a double-blinded randomized multicenter trial. The results were published online July 11 in Obstetrics & Gynecology.

Deborah A. Wing, MD, specialist in maternal-fetal medicine at the University of California, Irvine, and colleagues randomly assigned 678 women to receive a 200-μg misoprostol insert and 680 to receive a 10-mg dinoprostone vaginal insert in this phase 2 study. Misoprostol, which has been approved by the US Food and Drug Administration for the treatment of gastric ulcers, is widely used off-label for cervical ripening and labor induction.

"These results present in a very clear way, and with a very well-designed study, what the advantages and disadvantages of misoprostol are," Jeffery Ecker, MD, told Medscape Medical News. Dr. Eckert, who was not involved in the study, is chair, American College of Obstetrics and Gynecology on Obstetrical Practice and a specialist in high-risk obstetrics at Massachusetts General Hospital in Boston. "[E]very time someone is contracting too frequently, it does require a response and resources. That said, there are lots of reasons this can be done safely for a more prompt delivery, something everyone appreciates. It was not associated with any adverse outcomes."

However, the new data are unlikely to alter current practice because of the dose and formulation that were tested, according to Dr. Ecker. American Congress of Obstetricians and Gynecologists guidelines published in 2009 recommend a dose of 25 μg initially, with repeated administration of the same dose not more than every 3 to 6 hours. "It's a very different formulation,” Dr. Ecker said. “It's a very different dose. It doesn't say anything about misoprostol as it's currently being used, and has been used for a long time, and has been very well studied. It doesn't make me question the continued use of the 25 μg given vaginally."

In the current study, the misoprostol insert was associated with a shorter median time to vaginal delivery, at 21.5 hours (95% confidence interval [CI], 20.0 - 23.4 hours) compared with 32.8 hours (95% CI, 30.2 - 34.9 hours) for women using dinoprostone (P < .001). For nulliparous women, median time to vaginal delivery was 29.2 hours (95% CI, 25.4 - 32.7 hours) for misoprostol compared with 43.1 hours (95% CI, 37.9 - 48.8 hours) for dinoprostone (P < .001). For parous women, median time to vaginal delivery was 13.4 hours (95% CI, 12.5 - 14.8 hours) for misoprostol compared with 20.1 hours (95% CI, 17.8 - 22.8 hours) for dinoprostone (P < .001).

Adverse event rates were similar between the 2 groups, at 55.5% for misoprostol and 54.6% for dinoprostone (P = .74). The pregnancies with tachysystole requiring intervention were more common in women using misoprostol, at 13.3% compared with 4.0% (relative risk, 3.34; 95% CI, 2.20 - 5.07; P < .05).

Cesarean delivery rates were similar between the 2 groups, at 26.0% in the misoprostol cohort and 27.1% in the dinoprostone group.

Misoprostol was also associated with a quicker time to delivery when cesarean deliveries were included in the analysis, with 18.3 hours being the median time to delivery for the misoprostol treatment group and 27.3 hours for the dinoprostone group (P < .001). Time to active labor was 12.1 hours in the misoprostol group and 18.6 hours in the dinoprostone cohort (P < .001). Nearly three quarters of the women in the dinoprostone group received predelivery oxytocin compared to just less than half of the women in the misoprostol group (P < .001). There were also fewer labors longer than 24 hours with misoprostol: 67.7% (459) women delivered with 24 hours with misoprostol compared with 40.7% (277) in the dinoprostone group.

In an accompanying editorial, Dwight J. Rouse, MD, associated editor of the journal, writes that despite the study's "methodologic rigor, I do not think this trial justifies the clinical use of the 200-microgram misoprostol vaginal insert."

Dr. Rouse questioned the wisdom of greatly increasing the number of contractions with misoprostol, as half of the women in the misoprostol group experienced tachysystole compared with a quarter of women using dinoprostone. "Much of the difference [in outcomes]...is probably explained by the fact that the misoprostol insert led to more uterine contractions, which is not necessarily a good thing, just as driving 100 miles per hour may get you home from work a bit earlier, but is usually not a good idea," he writes.

Dr. Wing is a consultant for Ferring and former recipient of research support from Cytokine PharmaSciences (now a wholly owned subsidiary of Ferring) to conduct this trial. Two coauthors have received research support from Ferring, one of whom also attended an advisory board as a panel member and consultant. One coauthor works for Ferring, and one coauthor is a former employee and current consultant to Ferring. The other authors, Dr. Rouse, and Dr. Ecker have disclosed no relevant financial relationships.

Obstet Gynecol. 2013;122:201-209. Article abstract, Editorial extract


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