SAN FRANCISCO – A new vaginal prostaglandin product speeds the time to delivery in women needing labor induction and does not appear to compromise safety, according to a phase III trial reported at the Pregnancy Meeting, the annual meeting of the Society of Maternal-Fetal Medicine.
The randomized trial, known as EXPEDITE, enrolled 1,358 women, all of whom had uncomplicated term or near-term pregnancies and needed cervical ripening and labor induction.
Dr. Deborah A. Wing
The main results showed that the time between study drug insertion and vaginal delivery (the trial’s primary outcome) was 21.5 hours with an investigational misoprostol vaginal insert delivering 200 mcg of the drug (MVI 200), compared with 32.8 hours with the commercially available dinoprostone vaginal insert (DVI), lead investigator Dr. Deborah A. Wing reported.
In terms of safety, about a quarter of women had a cesarean delivery, with no significant difference between groups, although the trial unexpectedly lacked sufficient power to assess this difference. The rate of intrapartum adverse events thought to be related to the study drug was higher with MVI 200.
"Use of MVI 200 reduced the time to vaginal delivery by more than 11 hours compared with DVI," she commented. "Both treatments had similar cesarean delivery rates. Abnormal labor affecting the fetus and fetal heart rate disorder considered related to the study drug were more common with MVI 200."
An attendee asked, "Why do you think that while the labor was shortened, there wasn’t a reduction in the risk of cesarean delivery?"
"I think it’s because we have developed an agent or a device with an agent that is very good at getting the process of human parturition to be turned on. There are still myriad factors that we do not understand about what makes human parturition be successful if one agrees that success is defined as vaginal delivery," replied Dr. Wing, who is a maternal-fetal medicine specialist at the University of California, Irvine.
Another attendee disagreed with the choice of the trial’s primary outcome, saying, "You chose time as a primary outcome over patient safety – that outcome is a secondary one – and I’m afraid that your study is really underpowered to rule out a difference in neonatal outcomes. So why didn’t you use neonatal and maternal outcomes as the primary ones to be sure that we are not harming the kids by these fast deliveries, because I think that’s what’s happening – we are pushing them out early and some of them are eventually harmed by that."
"There is no doubt in my mind and no doubt in the sponsor’s mind that safety – both maternal and neonatal – is number one. You are correct, these trials I don’t think can be conducted in any way, shape, or form in today’s world of sufficient magnitude to be able to address the issues of maternal or neonatal safety," Dr. Wing said.
She noted, for example, that a recent analysis included in a Cochrane review on the use of oral misoprostol for labor induction suggested that adequately assessing the outcome of maternal death would require 160,000 women per treatment arm. "Clearly, there are other things that happen more commonly, but the magnitude of those trials is still on the order of tens of thousands of women. ... So, yes, safety is a primary concern. Efficacy has also been a concern, and part of the focus has been guided by the U.S. Food and Drug Administration and their many years of working with [the manufacturer] to get us where we are."
A third attendee said, "My understanding is that the MVI is a 24-hour drug and that the DVI is a 12-hour drug, and in this blinded trial, they have each received the drug for 24 hours. So technically, if I’m thinking correctly, the DVI group went 12 hours with no treatment and delivered 11 hours later. How can you address that with the time difference?"
"Yes, the package insert for the Cervidil [the brand name of the DVI] says 12 hours, but the protocol was designed for 24 hours of exposure to the DVI, with the blessing of the U.S. Food and Drug Administration, so that all women in both groups had the opportunity to be exposed to the drug for up to a day," Dr. Wing said.
Women participating in the trial were from multiple institutions in North America and had a gestation of at least 36 weeks, a modified Bishop score of 4 or less, and a parity of 3 or less. Two-thirds were nulliparous.