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.