Clinical trial NCT04949633: Oxytocin vs Prostaglandins for Labor Induction of Women With an Unfavorable Cervix After 24h of Cervical Ripening
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cervical Ripening
Unfavorable Cervix
Keywords: cervical ripening
oxytocin
prostaglandin
cesarean delivery
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2021-07-02
Enrollment: 1494
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* Pregnant woman
* ≥ 18 years old
* With a singleton cephalic pregnancy
* Between ≥37+0 weeks and ≤ 42+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 or with more than 3 contractions / 10 minutes

Primary outcomes:
measure: Cesarean delivery rate
timeFrame: Up to 2 days after intervention
Secondary outcomes:
measure: Time from intervention to delivery in hours
timeFrame: Up to 2 days after intervention
measure: The proportion of women who delivered within 12 hours of the intervention
timeFrame: Up to 12 hours after intervention
measure: Maternal satisfaction, assessed with the self administered ACE Questionnaire for Assessing Childbirth Experience (QACE)
timeFrame: 1 month
measure: The proportion of women who require induction with oxytocin (for women in the control group)
timeFrame: Up to 2 days after intervention
measure: The indications of caesarean in case of caesarean delivery
timeFrame: Up to 2 days after intervention
measure: The proportion of women with an instrumental delivery
timeFrame: Up to 2 days after intervention
measure: The indications for the use of instruments in case of instrumental delivery
timeFrame: Up to 2 days after intervention
measure: The proportion of women suspected of per-partum infection
timeFrame: Up to 2 days after intervention
measure: The proportion of women with post-partum haemorrhage
timeFrame: Up to 1 day after delivery
measure: The proportion of women with severe Post-partum haemorrhage
timeFrame: Up to 2 days after intervention
measure: The proportion of women with anal sphincter injury at delivery
timeFrame: Up to 2 days after intervention
measure: The proportion of women who need blood transfusion
timeFrame: Up to 2 days after intervention
measure: The proportion of women who need for antibiotics
timeFrame: Up to 2 days after intervention
measure: The proportion of women admitted to intensive care unit
timeFrame: Up to 2 days after intervention
Other outcomes:
measure: Number and rate of children with an Apgar score under 7
timeFrame: Up to 2 days after intervention
measure: Number and rate of children with neonatal acidosis defined as umbilical arterial pH <7,00
timeFrame: Up to 2 days after intervention
measure: Number and rate of children with early neonatal infection
timeFrame: Up to 7 days after delivery
measure: Number and rate of children admitted in an intensive care unit
timeFrame: Up to 7 days after delivery
measure: Proportion of incremental cost-effect pairs
timeFrame: Up to 8 weeks
Locations:
city: Angers
country: France
facility: Gynaecology-obstetrics, University Hospital, Angers
city: Bordeaux
country: France
facility: Gynaecology-obstetrics, University Hospital, Bordeaux
city: Brest
country: France
facility: Gynaecology-obstetrics, University Hospital, Brest
city: Clermont-Ferrand
country: France
facility: Gynaecology-obstetrics, University Hospital, Clermont-Ferrand
city: Marseille
country: France
facility: Gynaecology-obstetrics, Hospital St Joseph, Marseille
city: Nantes
country: France
facility: Gynaecology-obstetrics, University Hospital, Nantes
city: Paris
country: France
facility: Gynaecology-obstetrics, Port Royal Maternity Hospital, Paris
city: Poitiers
country: France
facility: Gynaecology-obstetrics, University Hospital, Poitiers
city: Saint-Étienne
country: France
facility: Gynaecology-obstetrics, University Hospital, Saint Etienne
city: Tours
country: France
facility: Gynaecology-obstetrics, University Hospital, Tours
Study officials:
affiliation: University Hospital, Tours
name: Caroline DIGUISTO, MD
role: STUDY_DIRECTOR
References: