Oxytocin versus Prostaglandins for labor Induction of women with an unfavorable Cervix after 24 hours of cervical ripening: a multicenter non inferiority randomized trial

2024-517675-20-00 Protocol DR200090 Phase III and Phase IV (Integrated) Ongoing, recruiting

Start 28 Sep 2021 · Status Ongoing, recruiting · 1 EU/EEA countries · 14 sites · Protocol DR200090

Overview

Sponsor-declared trial summary

Phase Phase III and Phase IV (Integrated)
Status Ongoing, recruiting
Participants planned 1,494
Countries 1
Sites 14

Labor Induction of women with an unfavorable Cervix after 24 hours of cervical ripening

To show that, among women with an unfavorable cervix after a first cervical ripening, induction of labor with oxytocin is not associated with an increased risk of caesarean delivery in comparison with repeating cervical ripening with prostaglandins.

Key facts

Sponsor
Centre Hospitalier Regional Universitaire De Tours
Participant type
Patients
Age range
18-64 years
Gender
Female
Therapeutic area
Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]
Trial duration
28 Sep 2021 → ongoing
Decision date (initial)
2024-12-10
Transition trial
Yes
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
DGOS/ PHRC national

External identifiers

EU CT number
2024-517675-20-00
EudraCT number
2021-000989-15
ClinicalTrials.gov
NCT04949633

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To show that, among women with an unfavorable cervix after a first cervical ripening, induction of labor with oxytocin is not associated with an increased risk of caesarean delivery in comparison with repeating cervical ripening with prostaglandins.

Secondary objectives 3

  1. To show that, among women with an unfavorable cervix after a first cervical ripening, induction of labor with oxytocin in comparison with repeated cervical ripening is associated with a reduced time to delivery and length of stay and increased satisfaction of women.
  2. Also to show that maternal and neonatal morbidity are similar for these two strategies.
  3. To evaluate, in a joint analysis, that inducing labor with oxytocin is clinically not inferior in terms of caesarean delivery rate and not more expensive (economic non inferiority) in comparison with repeated cervical ripening, in women with an unfavorable cervix after a first cervical ripening.

Conditions and MedDRA coding

Labor Induction of women with an unfavorable Cervix after 24 hours of cervical ripening

VersionLevelCodeTermSystem organ class
20.0 LLT 10023540 Labor induced 10036585

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Inclusion
Women who will require an induction of labor with cervical ripening will be informed of the study’s objectives by midwives/physicians and all their questions will be answered. To this point all inclusion and exclusion criteria may be verified apart from the bishop score and the foetal heart rate. Twenty-four hours after cervical ripening, women who will not be in labor will have a cervical examination (which will determine the Bishop score) and a fetal CardioTocoGraphy (CTG) (which will allow to analyse the fetal heart rate) to verify the absence of the two possible exclusion criteria. Women should be allowed to have as much time as necessary to decide whether or not they wish to participate to the study. if they agree to participate, inclusion can be made with consent signature and randomization.
 Randomised Controlled None Experimental group: 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.
Control group: Control group: women randomized in the control group will undergo a second cervical ripening lasting a maximum of 24 hours with prostaglandins
2 Follow-up
After randomization women in the experimental group will be admitted to the labor ward to undergo induction of labor with intra-veinous oxytocin. Women randomized in the control group will undergo a second cervical ripening with prostaglandins. The second cervical ripening will last a maximum of 24 hours. At the end of the second cervical ripening, women not in labor will be transferred to the labor ward for induction of labor with oxytocin. After delivery women will receive standard care. When women will leave the maternity unit they will be given short paper questionnaire. They will be recommended to fill-in the questionnaire four weeks after delivery and to send it back to the unit.
 Randomised Controlled None Experimental group: 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.
Experimental group: Women randomized in the control group will undergo a second cervical ripening lasting a maximum of 24 hours with prostaglandins

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Pregnant woman
  2. ≥ 18 years old
  3. With a singleton cephalic pregnancy
  4. At a term ≥37+0 weeks of gestation
  5. Gestational age estimated from the first trimester ultrasound (realized between 11+0 and 13+6 weeks of gestation)
  6. With a medical indication of labor with a previous pharmacological or mechanical cervical ripening of 24 hours
  7. Bishop score ≤ 6 at inclusion (unfavorable cervix)
  8. Written informed consent
  9. French health insurance policy holder

Exclusion criteria 8

  1. Any measures of legal protection
  2. Prior caesarean section or uterine scar
  3. Contra-indications to a vaginal delivery
  4. Foetus with suspected severe congenital abnormalities
  5. Pathological foetal heart rate
  6. Contra-indications to prostaglandins (ANGUSTA®, PROPESS®, PROSTINE®)
  7. Contra-indications for using oxytocin
  8. Woman in labor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Rate of caesarean delivery, whatever the indication of the caesarean delivery

Secondary endpoints 34

  1. Time from intervention to delivery in hours
  2. Delivery within 12 hours
  3. Maternal satisfaction
  4. Need for induction with oxytocin (for women in the control group)
  5. Indication of caesarean in case of caesarean delivery
  6. Instrumental delivery
  7. Indication for the use of instruments in case of instrumental delivery
  8. Oxytocin augmentation
  9. Uterine hyperstimulation
  10. Suspicion of per-partum infection
  11. Post-partum haemorrhage
  12. Severe post-partum haemorrhage
  13. Anal sphincter injury
  14. Blood transfusion
  15. Need for antibiotics
  16. Length of hospital stay
  17. Cardiorespiratory arrest
  18. Damage to internal organs
  19. Hysterectomy for any complications resulting from birth
  20. Pulmonary embolus
  21. Stroke
  22. Admission to intensive care unit
  23. Maternal death
  24. Neonatal morbidity: birth trauma
  25. Neonatal morbidity: hypoxic ischaemic encephalopathy
  26. Neonatal morbidity: need for therapeutic hypothermia
  27. Neonatal morbidity: meconium aspiration syndrome
  28. Neonatal morbidity: need for respiratory support
  29. Neonatal morbidity: neonatal seizures
  30. Neonatal morbidity: neonatal acidosis
  31. Neonatal morbidity: Early neonatal infection
  32. Neonatal morbidity: Admission in an intensive care unit
  33. Neonatal morbidity: death of the baby
  34. Proportion of incremental cost-effect pairs that lies into the non-inferiority area, for various values of economic non–inferiority margin, and for a constant clinical non-inferiority margin (7%).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

OXYTOCINE PANPHARMA 5 UI/1 ml, solution injectable

PRD928155 · Product

Active substance
Oxytocin
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS USE
Max daily dose
10 U unit(s)
Max total dose
10 U unit(s)
Max treatment duration
1 Week(s)
Authorisation status
Authorised
ATC code
H01BB02 — OXYTOCIN
Marketing authorisation
34009 584 140 2 2
MA holder
PANPHARMA
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 3

ANGUSTA 25 microgrammes, comprime

PRD5910309 · Product

Active substance
Misoprostol
Pharmaceutical form
TABLET
Route of administration
ORAL USE
Max daily dose
200 mg milligram(s)
Max total dose
200 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
G02AD06 — -
Marketing authorisation
34009 550 495 3 1
MA holder
NORGINE B.V.
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

PROPESS 10 mg, système de diffusion vaginal

PRD454514 · Product

Active substance
Dinoprostone
Pharmaceutical form
VAGINAL DELIVERY SYSTEM
Route of administration
VAGINAL USE
Max daily dose
10 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
G02AD02 — DINOPROSTONE
Marketing authorisation
34009 561 974 4 6
MA holder
FERRING S.A.S.
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

PROSTINE E2 2 mg/3 g, gel vaginal

PRD494900 · Product

Active substance
Dinoprostone
Pharmaceutical form
VAGINAL GEL
Route of administration
VAGINAL USE
Max daily dose
6 mg milligram(s)
Max total dose
6 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
G02AD02 — DINOPROSTONE
Marketing authorisation
34009 557 750 8 9
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

29 Total trials 17 Recruiting 4 Ended
Academic / Non-commercial
Sponsor organisation
Centre Hospitalier Regional Universitaire De Tours
Address
2 Boulevard Tonnelle
City
Tours Cedex 9
Postcode
37044
Country
France

Scientific contact point

Organisation
Centre Hospitalier Regional Universitaire De Tours
Contact name
Coordinating Investigator

Public contact point

Organisation
Centre Hospitalier Regional Universitaire De Tours
Contact name
Coordinating Investigator

Locations

1 EU/EEA country · 14 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 1,494 14
Rest of world — 0 —

Investigational sites

France

14 sites · Ongoing, recruiting
Assistance Publique Hopitaux De Paris
Gynaecology-Obstetrics, 27 Rue Du Faubourg Saint Jacques, 75014, Paris
University Hospital Of Clermont-Ferrand
Gynaecology-Obstetrics, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Centre Hospitalier Regional Et Universitaire De Brest
Gynaecology-Obstetrics, Boulevard Tanguy Prigent, 29200, Brest
Centre Hospitalier Universitaire De Bordeaux
Gynaecology-Obstetrics, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Universitaire D Orleans
Gynaecology-Obstetrics, 14 Avenue De L Hopital, Cs 86709, Orleans Cedex 2
Centre Hospitalier Regional Universitaire De Tours
Gynaecology-Obstetrics, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Centre Hospitalier Universitaire De Nantes
Gynaecology-Obstetrics, 38 Boulevard Jean Monnet, 44000, Nantes
Centre Hospitalier Universitaire De Saint Etienne
Gynaecology-Obstetrics, Avenue Albert Raimond, 42270, Saint Priest En Jarez
Hopital Saint Joseph
Gynaecology-Obstetrics, 26 Boulevard De Louvain, 13008, Marseille
Centre Hospitalier Universitaire De Poitiers
Gynaecology-Obstetrics, 2 Rue De La Miletrie, 86000, Poitiers
CHRU De Nancy
Gynaecology-Obstetrics, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Centre Hospitalier Regional D'Angers
Gynaecology-Obstetrics, 4 Rue Larrey, 49100, Angers
Les Hopitaux Universitaires De Strasbourg
Gynaecology-Obstetrics, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Hopital NOVO
Gynaecology-Obstetrics, 6 Avenue De L Ile De France, 95300, Pontoise

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2021-09-28 2021-09-28

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_PROTOCOL 2024-517675-20-00 4
Protocol (for publication) D1_Protocol SOC 2024-517675-20-00 3
Protocol (for publication) D1_Protocol TC 2024-517675-20-00 4
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF 1.1
Subject information and informed consent form (for publication) L2_Other subject information materiel Recruitement poster 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC ANGUSTA 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC OXYTOCINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC PROPESS 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC PROSTINE 2
Synopsis of the protocol (for publication) D1_Protocol synopsis EN 2024-517675-20-00 3.1
Synopsis of the protocol (for publication) D1_PROTOCOL SYNOPSIS FR 2024-517675-20-00 3.1
Synopsis of the protocol (for publication) D1_Protocol synopsis FR TC 2024-517675-20-00 3.1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-04 France Acceptable
2024-10-25
 2024-12-10
2 SUBSTANTIAL MODIFICATION SM-1 2025-07-16 France Acceptable
2025-09-19
 2025-10-08
3 SUBSTANTIAL MODIFICATION SM-2 2026-01-30 France Acceptable
2026-02-13
 2026-03-16