Atosiban for maintenance therapy of preterm labour delayed recurrence of labour but did not improve neonatal outcome

OBJECTIVE To determine the efficacy and safety of atosiban for maintenance therapy of preterm labour in women who have achieved uterine quiescence with i.v. atosiban treatment. DESIGN Multicentre, randomized, double-blind, placebo-controlled trial. Allocation was computer-generated, blocked, stratified by centre, and carried out at each centre's pharmacy using sealed envelopes. SETTING 51 centres in the USA. SUBJECTS 512 women who had been in preterm labour with intact membranes, cervical dilatation ≤ 3 cm, and live fetus(es) of gestational age 20 to < 34 (mean 31) weeks, but had achieved uterine quiescence after treatment with i.v. atosiban. 43% of women had Bishop score ≥ 4 and 9% of pregnancies were multiple gestation. One woman randomized to the placebo group did not receive treatment and was excluded from the analysis. INTERVENTION Two hundred and sixty-one women were randomized to receive continuous treatment with atosiban by subcutaneous infusion pump (30 μg/min) and 251 women to receive placebo. Treatment was discontinued at 36 weeks gestation, delivery, or progression of labour requiring an alternative tocolytic agent. Additional episodes of preterm labour were treated with i.v. atosiban, then maintenance therapy resumed, if appropriate. MAIN OUTCOME MEASURES Time to first recurrence of labour, proportion of women requiring i.v. atosiban treatment, neonatal outcomes, maternal side-effects. Efficacy analysis was by intention-to-treat, but safety analysis was by drug actually received (3% of subjects in the placebo group received some atosiban). MAIN RESULTS The median time to recurrence of labour was 32.6 days in the atosiban group and 27.6 days in the placebo group (P = 0.02, absolute treatment effect (ATE) 5.0 days). The proportion of women who required i.v. atosiban for recurrent preterm labour was 23.4% in the atosiban group and 30.7% in the placebo group (P = 0.06, relative risk (RR) 0.76, 95% CI 0.57-1.01)*. Injection site reaction was reported by 70% of women who received atosiban and 48% of those who received placebo (P < 0.0001*). The occurrences of maternal chest pain, tachycardia, and fetal distress were < 1% in both groups. The fetal/infant mortality rate was 1.7% with atosiban and 1.8% with placebo (P = 0.9*). There was no significant difference between groups in the proportion of women who delivered at < 37 weeks gestation (34 vs 38%), in mean birthweight, or in proportions of infants who were admitted to neonatal intensive care (21 vs 26%) or had respiratory distress syndrome (11 vs 11%) or intraventricular hemorrhage (6 vs 4%). CONCLUSION When used for maintenance therapy of preterm labour, atosiban significantly extended the time to first recurrence of labour, compared to placebo, but did not improve neonatal outcome.