An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: A randomized, double-blind, placebo-controlled trial with tocolytic rescue

OBJECTIVES: This study was designed to evaluate the efficacy and safety of the oxytocin receptor antagonist atosiban in the treatment of preterm labor . STUDY DESIGN: A multicenter, double-blind, placebo-controlled trial with to colytic rescue was designed. Five hundred thirty-one patients were randomiz ed to receive, and 501 received, either intravenous atosiban (n = 246) or p lacebo (n = 255), followed by subcutaneous maintenance with the assigned ag ent. Standard tocolytics as rescue tocolysis were permitted after 1 hour of either placebo or atosiban if preterm labor continued. The primary end poi nt was the time from the start of study drug to delivery or therapeutic fai lure. Secondary end points were the proportion of patients who remained und elivered and did not receive an alternate tocolytic at 24 hours, 48 hours, and 7 days. RESULTS: No significant difference was found in the time from start of trea tment to delivery or therapeutic failure between atosiban and placebo (medi an, 25.6 days vs 21.0 days, respectively; P=.6). The percentages of patient s remaining undelivered and not requiring an alternate tocolytic at 24 hour s, 48 hours, and 7 days were significantly higher in the atosiban group tha n in the control group (all P less than or equal to.008). A significant tre atment-by-gestational age interaction existed for the 48-hour and 7-day end points. Atosiban was consistently superior to placebo at a gestational age of greater than or equal to 28 weeks. Fourteen atosiban-treated patients a nd 5 placebo-treated patients were randomized at <24 weeks; the incidence o f fetal-infant deaths was higher for the atosiban group at <24 weeks. Mater nal-fetal adverse events were similar except for injection-site reactions, which occurred more often with atosiban. CONCLUSIONS: In this trial the treatment of patients in preterm labor with atosiban resulted in prolongation of pregnancy for up to 7 days for those a t a gestational age greater than or equal to 28 weeks, and this occurred wi th a low rate of maternal-fetal adverse effects. In addition, at a gestatio nal age greater than or equal to 28 weeks, the infant morbidity and mortali ty of atosiban-initiated standard care were similar to those with placebo-i nitiated standard care. Given that all patients in this study were eligible for tocolysis and that, in practice, nearly all patients who are eligible for a tocolytic receive one, the benefit of using atosiban is the placebo-l ike maternal-fetal side effect profile. These observations support the use of this oxytocin receptor antagonist in the treatment of patients in preter m labor with intact membranes. Efficacy and infant outcome data at <28 week s are inconclusive.