Induction of labor at term with vaginal misoprostol or a prostaglandin E2 pessary: a noninferiority randomized controlled trial.

BACKGROUND: Induction of labor is among the most common procedures for pregnant women. Only a few randomized clinical trials with relatively small samples have compared misoprostol with dinoprostone. Although their efficacy seems similar, their safety profiles have not been adequately evaluated, and economic data are sparse. OBJECTIVE: This study aimed to test the noninferiority of vaginal misoprostol (prostaglandin E1) (25 µg) to a slow-release dinoprostone (prostaglandin E2) pessary (10 µg) for induction of labor with an unfavorable cervix at term. STUDY DESIGN: This was an open-label multicenter randomized noninferiority trial at 4 university hospitals of the Research Group in Obstetrics and Gynecology between 2012 and 2015. We recruited women who underwent induction of labor for medical reasons, those with a Bishop score of ≤5 at ≥36 weeks' gestation, and those with a cephalic-presenting singleton pregnancy with no previous cesarean delivery. Women were randomly allocated to receive either vaginal misoprostol at 4-hour intervals (25 µg) or a 10-mg slow-release dinoprostone pessary. The primary outcome was the total cesarean delivery rate. Noninferiority was defined as a difference in the cesarean delivery rates between the groups of no more than 5%. Secondary outcomes included neonatal and maternal morbidity, vaginal delivery at <24 hours after starting the induction of labor process, and maternal satisfaction. RESULTS: The study included 1674 randomized women. The per-protocol analysis included 790 women in each group. The total cesarean delivery rates were 22.1% (n=175) in the misoprostol group and 19.9% (n=157) in the dinoprostone group, a difference of 2.2% (with an upper-bound 95% confidence limit of 5.6%) (P=.092). Results in the intention-to-treat analysis were similar. Neonatal and maternal morbidity rates were similar between groups. Vaginal delivery within 24 hours was significantly higher in the misoprostol group (59.3% vs 45.7%; P<.001) as was maternal satisfaction, assessed in the postpartum period by a visual analog scale (mean score, 7.1±2.4 vs 5.8±3.1; P<.001). CONCLUSION: The noninferiority of a 25-µg dose of vaginal misoprostol every 4 hours to the dinoprostone pessary for cesarean delivery rates after induction of labor at term could not be demonstrated, although the confidence limit of the difference barely exceeded the noninferiority margin. Nonetheless, given the small difference between these cesarean delivery rates and the similarity of neonatal and maternal morbidity rates in this large study, the clinical risk-to-benefit ratio justifies the use of both drugs.

Active Management of the Third Stage of Labor With a Combination of Oxytocin and Misoprostol to Prevent Postpartum Hemorrhage: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of misoprostol administered simultaneously with oxytocin as part of the active management of the third stage of labor. METHODS: This multicenter, double-blind, randomized, placebo-controlled trial recruited women in the first stage of labor with expected vaginal deliveries at 36-42 weeks of gestation. Exclusion criteria were multiple pregnancies, hypersensitivity to misoprostol, and cesarean delivery. Participants received routine intravenous oxytocin and were randomly allocated to receive 400 micrograms misoprostol or placebo orally immediately after delivery of the newborn. The primary outcome was postpartum hemorrhage (500 mL or greater within 2 hours of birth). Secondary outcomes included severe postpartum hemorrhage (1,000 mL or greater) and adverse maternal events such as fever, shivering, and nausea. Two groups of 1,550 women were required to demonstrate a 33% decrease of postpartum hemorrhage according to a two-tailed α at 0.05 with 80% power. An interim analysis was planned after 50% enrollment. RESULTS: Participant enrollment occurred from April 2010 to September 2013. Baseline characteristics were similar in the two groups. The study was discontinued after the planned interim analysis including 1,721 patients showed that misoprostol was not effective and was associated with significantly more adverse effects. The rate of postpartum hemorrhage was 8.4% (68/806) in the misoprostol and 8.3% (66/797) in the placebo group (P=.98), and rates of severe postpartum hemorrhage were 1.8% and 2.4%, respectively (P=.57). Maternal adverse events occurred significantly more frequently in the misoprostol group (for fever 30.4% in the misoprostol group compared with 6.3% in the placebo group, P<.001; for shivering 10.8% in the misoprostol group compared with 0.6% in the placebo group, P<.001). CONCLUSION: Misoprostol administered with prophylactic routine oxytocin did not reduce the rate of postpartum hemorrhage risk and increased the rate of adverse events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01113229.