BACKGROUND: Tocolytics are recommended in international guidelines as treatment for threatened preterm birth. Atosiban, an oxytocin receptor antagonist, is a registered tocolytic drug specifically indicated for the treatment of threatened preterm birth. Although tocolytics have been shown to delay birth, benefits on neonatal outcomes have not been demonstrated. In the APOSTEL 8 trial we aimed to assess superiority of tocolysis with atosiban compared with placebo in threatened preterm birth from 30 weeks and 0 days (30 METHODS: This was an international, multicentre, randomised, double-blind, superiority trial conducted in 26 hospitals in the Netherlands, England, and Ireland. After written informed consent, women aged 18 years or older with a singleton or twin pregnancy with threatened preterm birth from 30 FINDINGS: Between Dec 4, 2017, and July 24, 2023, a total of 755 participants were randomly assigned, of whom 752 were included in the intention-to-treat analysis (atosiban n=375, placebo n=377). The primary outcome occurred in 37 (8%) of 449 infants in the atosiban group and 40 (9%) of 435 in the placebo group (RR 0·90 [95% CI 0·58-1·40]). There were three (0·7%) and four (0·9%) infants who died, respectively (RR 0·73 [0·16-3·23])
all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups, and there were no maternal deaths. INTERPRETATION: We did not demonstrate superiority of atosiban over placebo in improving neonatal outcomes as treatment for threatened preterm birth from 30 FUNDING: ZonMw.