{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T02:05:42Z","timestamp":1769565942743,"version":"3.49.0"},"reference-count":30,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"unspecified","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"French Ministry of Health","award":["PHRCN-2020"],"award-info":[{"award-number":["PHRCN-2020"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,1,5]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Introduction<\/jats:title>\n 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\u2009hours and (2) increase patient satisfaction, compared with a low dose of oral misoprostol.<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n 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.<\/jats:p>\n After 12\u2009hours of PROM, women are randomly assigned to one of two study groups. One group is treated with a balloon catheter for 12\u2009hours, with oxytocin administered after 6\u2009hours. If the balloon is expelled earlier than 6\u2009hours after insertion and the cervix is still unfavourable, another balloon is placed. The other group (control) is treated with 25\u2009\u00b5g oral PGE1 every 2\u2009hours until labour starts. After a maximum of eight administrations and a timelapse of 4\u2009hours, 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\u2009women will be recruited in five university hospitals in France and randomised at a 1:1 ratio with stratification by study centre.<\/jats:p>\n Main inclusion criteria are nulliparous women with gestational age \u226537 weeks, PROM without labour beyond 12\u2009hours, 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.<\/jats:p>\n The hierarchical primary endpoints are: (1) Proportion of patients vaginally delivered <24\u2009hours 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\u2009hours 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%\u2009statistical 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%\u2009power).<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n NCT05568745<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-110425","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:10:55Z","timestamp":1769519455000},"page":"e110425","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Balloon plus oxytocin or oral misoprostol for labour induction in prelabour rupture of membranes (PROM): protocol for a randomised controlled trial (RUBAPRO2)"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct05568745","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8618-299X","authenticated-orcid":false,"given":"Marion","family":"Rouzaire","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexia","family":"Triolaire","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Vayssi\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-3625","authenticated-orcid":false,"given":"Lo\u00efc","family":"Sentilhes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Bordeaux Groupe Hospitalier Pellegrin, Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiphaine","family":"Barjat","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Saint-Etienne, Saint-\u00c9tienne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Luton","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Bic\u00eatre, Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Groupe de Recherche en Obstetrique et Gyn\u00e9cologie (GROG) Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Davoust","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Innovation (DRCI), Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Cabrespine","sequence":"additional","affiliation":[{"name":"Secteur Biom\u00e9trie et M\u00e9dico-\u00e9conomie, Direction de la Recherche Clinique et de l\u2019Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Pereira","sequence":"additional","affiliation":[{"name":"Secteur Biom\u00e9trie et M\u00e9dico-\u00e9conomie, Direction de la Recherche Clinique et de l\u2019Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Gallot","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"},{"name":"iGReD, CNRS, INSERM, Universit\u00e9 Clermont Auvergne, Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"2026012705102525000_16.1.e110425.1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/0002-9378(70)90378-9","article-title":"Premature rupture of the fetal membranes. A review","volume":"106","author":"Gunn","year":"1970","journal-title":"Am J Obstet Gynecol"},{"key":"2026012705102525000_16.1.e110425.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604183341601"},{"key":"2026012705102525000_16.1.e110425.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(97)70007-3"},{"key":"2026012705102525000_16.1.e110425.4","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.gofs.2017.05.001","article-title":"Pr\u00e9diction de l\u2019entr\u00e9e en travail sous 24 heures en cas de rupture des membranes \u00e0 terme","volume":"45","author":"Huret","year":"2017","journal-title":"Gyn\u00e9cologie Obst\u00e9trique Fertil S\u00e9nologie"},{"key":"2026012705102525000_16.1.e110425.5","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1080\/14767058.2020.1810230","article-title":"Term prelabor rupture of membranes: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF)","volume":"35","author":"S\u00e9nat","year":"2022","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2026012705102525000_16.1.e110425.6","doi-asserted-by":"crossref","unstructured":"Dare MR , Middleton P , Crowther CA , et al . Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev 2006;CD005302. doi:10.1002\/14651858.CD005302.pub2","DOI":"10.1002\/14651858.CD005302.pub2"},{"key":"2026012705102525000_16.1.e110425.7","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.ajog.2014.12.034","article-title":"Antibiotic prophylaxis for term or near-term premature rupture of membranes: metaanalysis of randomized trials","volume":"212","author":"Saccone","year":"2015","journal-title":"Am J Obstet Gynecol"},{"key":"2026012705102525000_16.1.e110425.8","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1097\/AOG.0b013e31826e46bc","article-title":"Antibiotic prophylaxis in premature rupture of membranes at term: a randomized controlled trial","volume":"120","author":"Passos","year":"2012","journal-title":"Obstet Gynecol"},{"key":"2026012705102525000_16.1.e110425.9","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1034\/j.1600-0412.1998.770308.x","article-title":"Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM","volume":"77","author":"Cararach","year":"1998","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2026012705102525000_16.1.e110425.10","unstructured":"Ovalle A , Gomez R , Martinez MA , et al . Antibiotic treatment of patients with term premature rupture of membranes: a randomized clinical trial. Prenatal Neonat Med 1998;599\u2013606."},{"key":"2026012705102525000_16.1.e110425.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61484-0"},{"key":"2026012705102525000_16.1.e110425.12","first-page":"145","article-title":"Foley catheter versus vaginal misoprostol: randomized controlled trial (PROBAAT-M study) and systematic review and meta-analysis of literature","volume":"31","author":"Jozwiak","year":"2014","journal-title":"Am J Perinatol"},{"key":"2026012705102525000_16.1.e110425.13","article-title":"Mechanical methods for induction of labour","volume":"2023","author":"de Vaan","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"2026012705102525000_16.1.e110425.14","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001002"},{"key":"2026012705102525000_16.1.e110425.15","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3109\/14767058.2015.1027191","article-title":"Use of intracervical balloons and chorioamnionitis in term premature rupture of membranes","volume":"29","author":"Cabrera","year":"2016","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2026012705102525000_16.1.e110425.16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/jog.13551","article-title":"Double-balloon versus single-balloon catheter for cervical ripening and labor induction: A systematic review and meta-analysis","volume":"44","author":"Yang","year":"2018","journal-title":"J Obstet Gynaecol Res"},{"key":"2026012705102525000_16.1.e110425.17","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s00404-018-4713-9","article-title":"Single versus double-balloon catheters for the induction of labor of singleton pregnancies: a meta-analysis of randomized and quasi-randomized controlled trials","volume":"297","author":"Lajusticia","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"2026012705102525000_16.1.e110425.18","doi-asserted-by":"crossref","first-page":"101158","DOI":"10.1016\/j.ajogmf.2023.101158","article-title":"Induction of labor via Foley balloon catheter placement for 6 vs 12 hours in women with 1 previous cesarean delivery and unfavorable cervices: a randomized controlled trial","volume":"5","author":"Yogamoorthy","year":"2023","journal-title":"Am J Obstet Gynecol MFM"},{"key":"2026012705102525000_16.1.e110425.19","doi-asserted-by":"crossref","first-page":"101157","DOI":"10.1016\/j.ajogmf.2023.101157","article-title":"Six compared with 12 hours of Foley balloon placement for labor induction in nulliparous women with unripe cervices: a randomized controlled trial","volume":"5","author":"Appadurai","year":"2023","journal-title":"Am J Obstet Gynecol MFM"},{"key":"2026012705102525000_16.1.e110425.20","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/ijgo.15466","article-title":"Time matters: Cervical ripening balloon for 6 versus 12\u2009h-Retrospective comparison between two protocols","volume":"166","author":"Bleicher","year":"2024","journal-title":"Int J Gynaecol Obstet"},{"key":"2026012705102525000_16.1.e110425.21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000009986","article-title":"Balloon catheter for induction of labor in nulliparous women with prelabor rupture of the membranes at term. A preliminary report","volume":"46","author":"Wolff","year":"1998","journal-title":"Gynecol Obstet Invest"},{"key":"2026012705102525000_16.1.e110425.22","doi-asserted-by":"publisher","DOI":"10.7556\/jaoa.2014.137"},{"key":"2026012705102525000_16.1.e110425.23","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1055\/s-0036-1580608","article-title":"Foley Catheter or Oral Misoprostol for Induction of Labor in Women with Term Premature Rupture of Membranes: A Randomized Multicenter Trial","volume":"33","author":"Kruit","year":"2016","journal-title":"Am J Perinatol"},{"key":"2026012705102525000_16.1.e110425.24","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11061525","article-title":"Double Balloon Catheter (Plus Oxytocin) versus Dinoprostone Vaginal Insert for Term Rupture of Membranes: A Randomized Controlled Trial (RUBAPRO)","volume":"11","author":"Devillard","year":"2022","journal-title":"J Clin Med"},{"key":"2026012705102525000_16.1.e110425.25","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11144217","article-title":"Cross-Cultural Adaptation and Psychometric Properties of the French Version of the EXIT to Measure Women\u2019s Experiences of Induction of Labor","volume":"11","author":"Guiguet-Auclair","year":"2022","journal-title":"J Clin Med"},{"key":"2026012705102525000_16.1.e110425.26","unstructured":"Cohen J . Statistical power analysis for the behavioural sciences. Hillsdale, NJ: Lawrence Erlbaum Associates, 1988."},{"key":"2026012705102525000_16.1.e110425.27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejogrb.2016.12.032","article-title":"Measuring women\u2019s experience of induction of labor using prostaglandin vaginal gel","volume":"210","author":"Beckmann","year":"2017","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2026012705102525000_16.1.e110425.28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/01443615.2017.1329284","article-title":"Induction of labour in term premature rupture of membranes; oxytocin versus sublingual misoprostol; a randomised clinical trial","volume":"38","author":"Pourali","year":"2018","journal-title":"J Obstet Gynaecol"},{"key":"2026012705102525000_16.1.e110425.29","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.3109\/14767058.2015.1121477","article-title":"Pregnancy outcomes after failed cervical ripening with prostaglandin E2 followed by Foley balloon catheter","volume":"29","author":"Mizrachi","year":"2016","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2026012705102525000_16.1.e110425.30","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1067\/S0002-9378(03)00845-7","article-title":"The MisoPROM study: A multicenter randomized comparison of oral misoprostol and oxytocin for premature rupture of membranes at term","volume":"189","author":"Mozurkewich","year":"2003","journal-title":"Am J Obstet Gynecol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-110425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:10:59Z","timestamp":1769519459000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-110425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,27]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/bmjopen-2025-110425"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-110425","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}