NEW ORLEANS – Use of an investigational vaginal misoprostol insert significantly reduced the time to vaginal delivery, compared with a vaginal dinoprostone insert, and also reduced the need for maternal and neonatal antibiotics in both nulliparous and parous women undergoing labor induction, according to findings from a randomized, double-blind, phase III study.
Time to vaginal delivery was a mean of 29.2 hours in 441 nulliparous women who were treated with the 200-mcg controlled-release misoprostol vaginal insert (MVI) for labor induction, compared with 43.1 hours in 451 nulliparous women treated with a 10-mg controlled-release dinoprostone vaginal insert (DVI). Time to vaginal delivery was a mean of 13.4 hours in 237 parous women treated with MVI, compared with 20.1 hours in 229 parous women treated with DVI, Dr. R. Lamar Parker reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.
Dr. Deborah A. Wing
The rate of cesarean delivery did not differ between the treatment groups (34.5% vs. 37.3% for nulliparous women treated with MVI and DVI, respectively, and 10.1% and 7.0% for parous women treated with MVI and DVI, respectively), said Dr. Parker, a gynecologist in group practice in Winston-Salem, N.C.
The groups also did not differ with respect to the rates of intrapartum, postpartum, or neonatal adverse events, most of which were mild or moderate, but the MVI group did experience more uterine activity–related adverse events, including tachysystole requiring intervention (13.3% vs. 4% in the MVI vs. DVI groups).
In another analysis of the study data, Dr. Deborah A. Wing and her colleagues found that MVI also significantly shortened the time to any delivery mode, compared with DVI (18.3 vs. 27.3 hours), and significantly shortened the duration of both the latent and active phases of labor (12.1 vs. 18.6 hours, and 4.8 vs. 6.9 hours, for the latent and active phases, respectively).
Significant reductions in the duration of latent and active labor with MVI vs. DVI treatment occurred in both nulliparous and parous women.
Shorter duration of these labor phases, regardless of the treatment used for labor induction, was associated with a significant reduction in the need for intrapartum, postpartum, and neonatal antibiotics, Dr. Wing, professor of clinical obstetrics and gynecology at the University of California, Irvine, and Long Beach Memorial Medical Center in Long Beach, Calif., reported in a separate poster.
Significantly fewer women who received MVI, compared with those who received DVI, required antibiotics during the intrapartum period (relative risk, 0.65) and postpartum period (RR, 0.55).
Also, antibiotics were required less often during the intrapartum, postpartum, and neonatal periods for both women and neonates when active or latent labor was shorter than the median duration, and when the total time to delivery and the duration of labor from rupture of membranes to delivery was shorter than the median duration, Dr. Wing noted.
Women included in this multicenter study were aged 18 years or older (mean of 26 years), had reached 36 weeks’ or more gestation, had parity of 3 or less, and had body mass index of 50 kg/m2 or less at study entry. All had a baseline modified Bishop score of 4 or less (mean of 2.4 and 2.3 in the MVI and DVI groups, respectively) and required labor induction.
Those with pregnancy-related or fetal complications were excluded.
The findings are of note, because in the United States nearly a quarter of deliveries involve labor induction.
"While many methods are used, the American College of Obstetricians and Gynecologists and the World Health Organization recommend low-dose prostaglandins for cervical ripening prior to induction of labor," the authors wrote.
Currently, DVI (PEG2), which is available as a vaginal insert or a vaginal gel, is the only Food and Drug Administration–approved prostaglandin for this purpose. Oral misoprostol, a prostaglandin E, is approved for prevention of gastric ulcers in patients using NSAIDS, but misoprostol tablets are often used off-label either orally or vaginally to induce labor, they said.
The tablet splitting and repeat administration required for vaginal use of oral misoprostol increases the likelihood of inaccurate dosing, they explained.
MVI (PEG1), however, is a controlled-release vaginal insert that can remain in place for 24 hours. It can also be removed – thereby terminating drug administration - at the onset of active labor or in the event of adverse effects, they said.
A new drug approval application for MVI was accepted for review by the FDA in October 2012.
This study was sponsored by Ferring Pharmaceuticals. Dr. Parker and Dr. Wing reported serving as consultants to Ferring Pharmaceuticals and formerly receiving research support from Cytokine PharmaSciences, which is a wholly owned subsidiary of Ferring Pharmaceuticals.