Misoprostol as Oral Solution or Oral Tablet for Induction of Labour (MISOBEST): A Randomised Controlled Non-Inferiority Trial.

Abstract

To assess if off-label oral solution of misoprostol compared with licensed oral tablet of misoprostol approved for induction of labour (IOL) is as efficient in resulting in vaginal delivery within 24 h, using a non-inferiority design. Prospective, randomised, non-inferiority, open-label, blinded endpoint trial. Two tertiary level hospitals, Stockholm, Sweden, January 2022 to May 2023. In all, 874 women, without previous caesarean section, with an unripe cervix and a singleton, cephalic foetus at 37 + 0 to 42 + 0 gestational weeks, with a normal cardiotocography, planned for IOL were included. Women were randomised 1:1 to intervention (25 μg oral solution of misoprostol) or control (25 μg oral tablet of misoprostol) two-hourly for a maximum of eight doses. Subsequent methods of induction followed clinical practice. The primary outcome was vaginal delivery within 24 h tested using non-inferiority testing procedures at a non-inferiority margin of 5 percentage points. Secondary efficacy outcomes were tested for superiority of either treatment. Analyses were by intention-to-treat. There were 207 (47.4%) vaginal deliveries within 24 h for women receiving oral solution and 192 (43.9%) vaginal deliveries within 24 h for women receiving oral tablet, establishing non-inferiority with an absolute risk difference of 3.4% (95% CI -3.2% to 10.0%). Women receiving oral solution required fewer doses to reach active labour than women receiving oral tablet (5.7 vs. 6.1, p = 0.007). There were no significant differences for other secondary or safety outcomes. Off-label oral solution of misoprostol was non-inferior to the licensed oral tablet regarding efficacy of IOL defined as vaginal delivery within 24 h. Clinicaltrials.gov identifier: NCT05424445.