Balloon plus oxytocin or oral misoprostol for labour induction in prelabour rupture of membranes (PROM): protocol for a randomised controlled trial (RUBAPRO2).

introductionThe optimal strategy for induction of labour (IOL) in cases of prelabour rupture of membranes (PROM) with an unfavourable cervix is elusive. No study conducted in nulliparous women has shown any one induction method to be superior to any other. In this project, we seek to determine whether IOL with balloon catheter and oxytocin can (1) increase rate of delivery <24 hours and (2) increase patient satisfaction, compared with a low dose of oral misoprostol. METHODS AND ANALYSIS: We are conducting a multicentre, randomised, controlled, open-label therapeutic trial with two parallel arms on nulliparous women with unfavourable cervix showing PROM at term without spontaneous labour.After 12 hours of PROM, women are randomly assigned to one of two study groups. One group is treated with a balloon catheter for 12 hours, with oxytocin administered after 6 hours. If the balloon is expelled earlier than 6 hours after insertion and the cervix is still unfavourable, another balloon is placed. The other group (control) is treated with 25 µg oral PGE1 every 2 hours until labour starts. After a maximum of eight administrations and a timelapse of 4 hours, if there are no effective uterine contractions, the induction is continued with oxytocin infusion and epidural analgesia if the patient requests it. A total of 520 women will be recruited in five university hospitals in France and randomised at a 1:1 ratio with stratification by study centre.Main inclusion criteria are nulliparous women with gestational age ≥37 weeks, PROM without labour beyond 12 hours, unfavourable cervix (Bishop score <6), and singleton pregnancy with cephalic presentation. Main exclusion criteria are contraindication for vaginal delivery, oxytocin, balloon or misoprostol, intrauterine infection, scarred womb, suspicion of genital herpes, known HIV seropositivity, abnormal fetal heart rate and fetal death.The hierarchical primary endpoints are: (1) Proportion of patients vaginally delivered <24 hours and (2) patient satisfaction according to an EXIT survey before hospital discharge. Three dimensions are explored on the EXIT scale: time taken to give birth, discomfort with IOL and experience of subsequent contractions. We hypothesise that the rate of delivery <24 hours will be 15% higher in the group induced with balloon plus oxytocin (estimated at about 85%) compared with the misoprostol group (estimated at about 70%) (with a two-sided type-1 error of 0.05 and 90% statistical power). For the EXIT dimensions, we aim to demonstrate a difference greater than an effect size of 0.4 (with two-sided type-1 error at 0.017 and 95% power). ETHICS AND DISSEMINATION: The RUBAPRO2 trial was approved by the French national agency for drug safety and committee for protection of persons involved in biomedical research on 15 September 2022. Informed written consent will be obtained from all participants. TRIAL REGISTRATION NUMBER: NCT05568745.