{
  "abstract": "Introduction The 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.",
  "authors": [
    {
      "affiliations": [
        "Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Marion Rouzaire"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Alexia Triolaire"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"
      ],
      "name": "Christophe Vayssière"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Bordeaux Groupe Hospitalier Pellegrin, Bordeaux, France"
      ],
      "name": "Loïc Sentilhes"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Étienne, France"
      ],
      "name": "Thiphaine Barjat"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre, France"
      ],
      "name": "Dominique Luton"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France",
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France",
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Bordeaux Groupe Hospitalier Pellegrin, Bordeaux, France",
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Étienne, France",
        "Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre, France",
        "Department of Clinical Research and Innovation (DRCI), Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France",
        "Secteur Biométrie et Médico-économie, Direction de la Recherche Clinique et de l’Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France",
        "iGReD, CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France"
      ],
      "name": "Groupe de Recherche en Obstetrique et Gynécologie (GROG) Investigators"
    },
    {
      "affiliations": [
        "Department of Clinical Research and Innovation (DRCI), Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Estelle Davoust"
    },
    {
      "affiliations": [
        "Secteur Biométrie et Médico-économie, Direction de la Recherche Clinique et de l’Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Aurélie Cabrespine"
    },
    {
      "affiliations": [
        "Secteur Biométrie et Médico-économie, Direction de la Recherche Clinique et de l’Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Bruno Pereira"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France",
        "iGReD, CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France"
      ],
      "name": "Denis Gallot"
    }
  ],
  "title": "Balloon plus oxytocin or oral misoprostol for labour induction in prelabour rupture of membranes (PROM): protocol for a randomised controlled trial (RUBAPRO2)",
  "uid": "a7bd910d-3ab8-5168-a596-836cfe67f876"
}