Oxytocin vs Prostaglandins for Labor Induction of Women With an Unfavorable Cervix After 24h of Cervical Ripening (OPIC)

Oxytocine Versus Prostaglandines Pour le déclenchement du Travail Des Femmes Dont le Col Est défavorable après 24 Heures de Maturation Cervicale : Essai Multicentrique randomisé de Non infériorité

Twenty-two percent of deliveries in France are induced. In cases where labor is induced and cervix is unfavorable, cervical ripening prior oxytocin administration is advised in order to reduce the risk of cesarean delivery. Cervical ripening agents, pharmacological (prostaglandins) or mechanical are administered during 24 hours. After 24 hours, most women will be either delivered or in labor but 25% of women will require further induction of labor. For 16% of women who undergo cervical ripening, whatever the cervical ripening method, the cervix remains unchanged after 24 hours. The management of these women is not consensual and depends on the maternity unit where women are cared for.

This study seeks to identify the most appropriate strategy for the management of women with an unfavorable cervix after 24 hours of cervical ripening, a strategy which would be associated with the lowest maternal and perinatal morbidity but also with the best maternal satisfaction. Because both strategies are practiced in France, the trial would compare: induction of labor with oxytocin and repeated cervical ripening. The aim is to show that repeating cervical ripening is an unnecessary procedure. And more specifically that oxytocin administration is not associated with a higher caesarean delivery rate and that it reduces the time to delivery in comparison with cervical ripening with prostaglandins.

Study Overview

• Status: Recruiting
• Conditions: Unfavorable Cervix; Cervical Ripening
• Intervention / Treatment: Drug: Oxytocin; Drug: Prostaglandins

Detailed Description

Twenty-two percent of deliveries in France are induced. In cases where labor is induced and cervix is unfavorable, cervical ripening prior oxytocin administration is advised in order to reduce the risk of cesarean delivery. Cervical ripening agents, pharmacological (prostaglandins) or mechanical are administered during 24 hours. After 24 hours, most women will be either delivered or in labor but 25% of women will require further induction of labor. For 16% of women who undergo cervical ripening, whatever the cervical ripening method, the cervix remains unchanged after 24 hours. The management of these women is not consensual and depends on the maternity unit where women are cared for. In some units, women are admitted into labor ward for induction of labor with oxytocin. Elsewhere cervical ripening is repeated in order to obtain a favorable cervix and to reduce the risk of caesarean delivery.

This study seeks to identify the most appropriate strategy for the management of women with an unfavorable cervix after 24 hours of cervical ripening, a strategy which would be associated with the lowest maternal and perinatal morbidity but also with the best maternal satisfaction. Because both strategies are practiced in France, the trial would compare: induction of labor with oxytocin and repeated cervical ripening. The policy of induction of labor with oxytocin, being the simpler strategy, would be acceptable if it did not lead to a substantially proportion of women with caesarean deliveries compared with a second cervical ripening. This multicenter non inferiority randomized trial will recruit women with an unfavorable cervix (bishop score ≤ 6) after 24 hours of cervical ripening (pharmacological or mechanical) and randomize them to either induction of labor with oxytocin or to a second cervical ripening with prostaglandins. The aim is to show that repeating cervical ripening is an unnecessary procedure. And more specifically that oxytocin administration is not associated with a higher caesarean delivery rate and that it reduces the time to delivery in comparison with cervical ripening with prostaglandins.

• Study Type: Interventional
• Enrollment (Estimated): 1494
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Caroline DIGUISTO, MD; Phone Number: +33 02 47 47 47 39; Email: carolinediguisto@gmail.com

Study Locations

• France
  • Angers, France, 49033
    • Recruiting
    • Gynaecology-obstetrics, University Hospital, Angers
    • Contact: Guillaume LEGENDRE, MD-PhD
    • Principal Investigator: Guillaume LEGENDRE, MD-PhD
  • Bordeaux, France, 33076
    • Terminated
    • Gynaecology-obstetrics, University Hospital, Bordeaux
  • Brest, France, 29609
    • Recruiting
    • Gynaecology-obstetrics, University Hospital, Brest
    • Contact: Jordan POZZY, MD
    • Principal Investigator: Jordan POZZI, MD
  • Clermont-Ferrand, France, 63001
    • Terminated
    • Gynaecology-obstetrics, University Hospital, Clermont-Ferrand
  • Marseille, France, 13008
    • Terminated
    • Gynaecology-obstetrics, Hospital St Joseph, Marseille
  • Nancy, France, 54000
    • Not yet recruiting
    • Gynaecology-obstetrics, University Hospital, Nancy
    • Contact: Charline BERTHOLDT, MD
    • Principal Investigator: Charline BERTHOLDT, MD
  • Nantes, France, 44093
    • Recruiting
    • Gynaecology-obstetrics, University Hospital, Nantes
    • Contact: Norbert WINER, MD-PhD
    • Principal Investigator: Norbert WINER, MD-PhD
  • Orléans, France, 45100
    • Recruiting
    • Gynaecology-obstetrics, University Hospital, Orléans
    • Contact: Floranne MEUNIER, MD
    • Principal Investigator: Floranne MEUNIER, MD
  • Paris, France, 75014
    • Recruiting
    • Gynaecology-obstetrics, Port Royal Maternity Hospital, Paris
    • Contact: François GOFFINET, MD
    • Principal Investigator: François GOFFINET, MD
  • Poitiers, France, 86000
    • Terminated
    • Gynaecology-obstetrics, University Hospital, Poitiers
  • Saint-Etienne, France, 42270
    • Recruiting
    • Gynaecology-obstetrics, University Hospital, Saint Etienne
    • Principal Investigator: Tiphaine BARJAT, MD
    • Contact: Tiphaine Barjat, MD
  • Tours, France, 37044
    • Recruiting
    • Gynaecology-obstetrics, University Hospital, Tours
    • Contact: Franck PERROTIN, MD-PhD
    • Principal Investigator: Franck PERROTIN, MD-PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant woman
• ≥ 18 years old
• With a singleton cephalic pregnancy
• ≥37+0 weeks of gestation
• Gestational age estimated from the first trimester ultrasound (realized between 11+0 and 13+6 weeks of gestation)
• With a medical indication of labor with a previous pharmacological or mechanical cervical ripening of 24 hours
• Bishop score ≤ 6 at inclusion (unfavorable cervix)
• French health insurance policy holder
• Written informed consent

Exclusion Criteria:

• Any measures of legal protection
• Prior caesarean section or uterine scar
• Contra-indications to a vaginal delivery
• Foetus with suspected severe congenital abnormalities
• Pathological foetal heart rate
• Contra-indications to ANGUSTA® (oral misoprostol, cervical ripening agent)
• Contra-indications to PROPESS® (vaginal slow releasing system of dinoprostone, cervical ripening agent)
• Contra-indications to PROSTINE® (vaginal gel of dinoprostone, cervical ripening agent)
• Contra-indications for using oxytocin
• Woman in labor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction of labor; women randomized in the experimental group will be admitted to the labor ward to undergo induction of labor with intra-veinous oxytocin and early amniotomy. Oxytocin will be administered according to the French guidelines for induction of labor. Maximum oxytocin used should not exceed 10 UI.	Drug: Oxytocin; Induction of labor with oxytocin.
Active Comparator: Second cervical ripening; women randomized in the control group will undergo a second cervical ripening lasting a maximum of 24 hours with either: Vaginal slow releasing system of dinoprostone PROPESS® which is inserted in the vagina, against the cervix and left in place during 24 hours.; Oral misoprostol (ANGUSTA®) 25 µg every 2 hours, 8 times (maximum dosage should not exceed 200µg). Tablets will be given one at the time by midwives.; Vaginal gel of dinoprostone (2 mg PROSTINE®) every 6 hours, maximum dose of 6 mg. The choice of the cervical ripening agent will depend of the local protocol of the participating maternity unit. The choice between ANGUSTA®, PROPESS® and PROSTINE® will be made by investigators of each participating unit at the beginning of the trial. At the end of the second cervical ripening procedure women not in labor will be transferred to the labor ward for induction of labor with oxytocin.	Drug: Oxytocin; Induction of labor with oxytocin.; Drug: Prostaglandins; Second cervical ripening lasting a maximum of 24 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cesarean delivery rate	The main outcome is the rate of caesarean delivery, whatever the indication of the caesarean delivery	Up to 2 days after intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Time from intervention to delivery in hours	Up to 2 days after intervention
The proportion of women who delivered within 12 hours of the intervention	Up to 12 hours after intervention
Maternal satisfaction, assessed with the self administered ACE Questionnaire for Assessing Childbirth Experience (QACE)	1 month
The proportion of women who require induction with oxytocin (for women in the control group)	Up to 2 days after intervention
The indications of caesarean in case of caesarean delivery	Up to 2 days after intervention
The proportion of women with an instrumental delivery	Up to 2 days after intervention
The indications for the use of instruments in case of instrumental delivery	Up to 2 days after intervention
The proportion of women suspected of per-partum infection	Up to 2 days after intervention
The proportion of women with post-partum haemorrhage	Up to 1 day after delivery
The proportion of women with severe Post-partum haemorrhage	Up to 2 days after intervention
The proportion of women with anal sphincter injury at delivery	Up to 2 days after intervention
The proportion of women who need blood transfusion	Up to 2 days after intervention
The proportion of women who need for antibiotics	Up to 2 days after intervention
The proportion of women admitted to intensive care unit	Up to 2 days after intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and rate of children with an Apgar score under 7		Up to 2 days after intervention
Number and rate of children with neonatal acidosis defined as umbilical arterial pH <7,00		Up to 2 days after intervention
Number and rate of children with early neonatal infection		Up to 7 days after delivery
Number and rate of children admitted in an intensive care unit		Up to 7 days after delivery
Proportion of incremental cost-effect pairs	Health economic outcome	Up to 8 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Study Director: Caroline DIGUISTO, MD

Publications and helpful links

General Publications

• De Berti M, Le Gouge A, Monmousseau F, Gallot D, Sentilhes L, Winer N, Legendre G, Desbriere R, Girault A, Pozzi J, Gachon B, Barjat T, Perrotin F, Brunet-Houdard S, Diguisto C; Groupe de Recherche en Gynecologie Obstetrique. Oxytocin versus prostaglandins for labour Induction of women with an unfavourable cervix after 24 hours of cervical ripening (OPIC): protocol for an open multicentre randomised non-inferiority trial. BMJ Open. 2023 Apr 17;13(4):e058282. doi: 10.1136/bmjopen-2021-058282.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: oxytocin; prostaglandin; cervical ripening; cesarean delivery
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Fatty Acids; Lipids; Biological Factors; Eicosanoids; Fatty Acids, Unsaturated; Autacoids; Inflammation Mediators; Pituitary Hormones, Posterior; Pituitary Hormones; Oxytocin; Prostaglandins
• Other Study ID Numbers: DR200090; 2021-000989-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data after de-identification can be obtained by contacting the corresponding author
• IPD Sharing Time Frame: Data will be available immediately following publication and ending in 5 years
• IPD Sharing Access Criteria: Contact with the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No