Balloon + Oxytocin versus Oral Misoprostol to Induce labor in case of premature rupture of membranes (PROM) at term in nulliparous

2022-501142-30-00 Protocol PHRC N 2020 GALLOT Therapeutic use (Phase IV) Ended

Start 17 Jan 2023 · End 29 Aug 2025 · Status Ended · 1 EU/EEA countries · 5 sites · Protocol PHRC N 2020 GALLOT

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ended
Participants planned 520
Countries 1
Sites 5

pregnant women with premature rupture of membranes

to demonstrate higher rate of vaginal birth <24h by insertion of a balloon catheter + oxytocin after 6h, versus low dose of oral misoprostol (25 µg oral PGE1 every 2h) in case of unfavorable cervix beyond 12 hours of PROM in nulliparous and to compare patient satisfaction using EXIT survey translated in French language…

Key facts

Sponsor
CHU Gabriel-Montpied
Participant type
Patients
Age range
18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Trial duration
17 Jan 2023 → 29 Aug 2025
Decision date (initial)
2022-09-15
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

to demonstrate higher rate of vaginal birth <24h by insertion of a balloon catheter + oxytocin after 6h, versus low dose of oral misoprostol (25 µg oral PGE1 every 2h) in case of unfavorable cervix beyond 12 hours of PROM in nulliparous and to compare patient satisfaction using EXIT survey translated in French language before hospital discharge

Secondary objectives 3

  1. To compare the rate of caesarean sections in the two groups
  2. To compare the safety related to women of both induction methods in terms of maternal morbidities, uterine hyperstimulation, maternal infections and other reported adverse events (AEs)
  3. To compare the safety related to neonates of both induction methods in terms of neonatal morbidities, neonatal infections and other reported AEs

Conditions and MedDRA coding

pregnant women with premature rupture of membranes

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Labor induction
The study group is the balloon catheter group with addition of oxytocin as early as 6h after the catheter insertion. After 12 hours of balloon insertion, induction of labour is continued by oxytocin alone. The control group corresponds to induction with misoprostol 25µg given orally (oral prostaglandin E1). The same dose is delivered every 2 hours until labour onset with a maximum of 8 administrations. Oxytocin can be started at least 4 hours after the last misoprostol administration. Patients will be assigned by random allocation on a 1:1 basis in permuted blocks to either treatment group or control group using a dedicated, password-protected, SSL-encrypted website. To minimize the risk of imbalance between the study groups, the randomization will be stratified by trial site.
 Randomised Controlled None labor induction with balloon catheter and oxytocin: The study group is the balloon catheter group with addition of oxytocin as early as 6h after the catheter insertion. After 12 hours of balloon insertion, induction of labour is continued by oxytocin alone
labor induction with misoprostol: The control group corresponds to induction with misoprostol 25µg given orally (oral prostaglandin E1). The same dose is delivered every 2 hours until labour onset with a maximum of 8 administrations. Oxytocin can be started at least 4 hours after the last misoprostol administration.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Age > 18 years old
  2. Pregnant, Gestational age ≥ 37 weeks
  3. Singleton pregnancy with cephalic presentation
  4. Nulliparous
  5. PROM occurring ≥ 37 weeks + 0 day and without labour beyond 12 hours
  6. Unfavourable cervix (Bischop score < 6)
  7. Able to give her informed consent
  8. Ability to comply with the requirement of the study
  9. Covered by the French Social Security welfare system

Exclusion criteria 18

  1. Unable to understand French language
  2. Contraindication for vaginal delivery
  3. Loss of meconium amniotic fluid (LA)
  4. Temperature > 38.2°C
  5. Intrauterine infection
  6. IUGR with Doppler anomaly
  7. Fetus with expected polymalformative syndrome
  8. Scarred womb
  9. Suspicion of genital herpes
  10. Known HIV seropositivity
  11. Placenta praevia
  12. Fetal death
  13. Abnormal FHR (Fetal Heart Rate)
  14. Contraindication to misoprostol
  15. Contraindication to balloon
  16. Contraindication to oxytocin
  17. Patient subject to a legal protection order (curatorship or tutorship)
  18. Refusal to participate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Proportion of patients vaginally delivered <24h (binary endpoint Yes/No)
  2. Satisfaction of women concerning method of induction assessed between the second day after delivery (D2) and hospital discharge by the EXperience of Induction Tool (EXIT) validated in french language. Total score is not relevant29. So, three dimensions are explored and analyzed by EXIT scale: time taken to give birth, discomfort with IOL, experience of subsequent contractions.

Secondary endpoints 21

  1. Duration from rupture to beginning of induction
  2. Duration between IOL and delivery
  3. Duration of balloon exposure or misoprostol exposure
  4. Total dose of misoprostol received
  5. Bishop score on balloon removal
  6. Rate of balloon in place at H12
  7. Duration until full cervical dilatation
  8. Rate of spontaneous vaginal delivery or instrumental delivery
  9. Indication and rate of cesarean section
  10. Rate of post-partum hemorrhage
  11. Rate of fever during labour
  12. Rate of patients experiencing episode(s) of uterine hyperstimulation during labour
  13. Rate of endometritis
  14. Duration of hospital stay
  15. Birth weight
  16. Apgar < 7 at 5 min (binary endpoint Yes/No)
  17. pH umbilical artery
  18. Base defect and lactate (umbilical artery), at birth
  19. Rate of transfer to intensive care unit or neonatology unit
  20. Rate of maternal-fetal infection
  21. Age at hospital discharge

Investigational products

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

Test 1

Oxytocin

SUB09580MIG · Substance

Active substance
Oxytocin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
10 IU international unit(s)
Max total dose
10 IU international unit(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 1

Misoprostol

SUB08998MIG · Substance

Active substance
Misoprostol
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
200 µg microgram(s)
Max total dose
200 µg microgram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 3

Amoxicillin Sodium

SUB00503MIG · Substance

Active substance
Amoxicillin Sodium
Pharmaceutical form
POWDER FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
2 g gram(s)
Max total dose
2 g gram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Clindamycin

SUB06665MIG · Substance

Active substance
Clindamycin
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
1800 mg milligram(s)
Max total dose
3600 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Amoxicillin

SUB05481MIG · Substance

Active substance
Amoxicillin
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
3 g gram(s)
Max total dose
6 g gram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHU Gabriel-Montpied

4 Total trials 2 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
CHU Gabriel-Montpied
Address
58 Rue Montalembert
City
Clermont Ferrand
Postcode
63000
Country
France

Scientific contact point

Organisation
CHU Gabriel-Montpied
Contact name
Lise Laclautre

Public contact point

Organisation
CHU Gabriel-Montpied
Contact name
Lise Laclautre

Locations

1 EU/EEA country · 5 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 520 5
Rest of world — 0 —

Investigational sites

France

5 sites · Ended
Bicetre Hospital
gynécologie-obstétrique, 78 Rue Du General Leclerc, 94275, Le Kremlin Bicetre Cedex
University Hospital Of Clermont-Ferrand
gynécologie-obstétrique, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Centre Hospitalier Universitaire De Bordeaux
Gynécologie obstétrique, 1 Place Amelie Raba Leon, Cs 91286, Bordeaux Cedex
CHU De Toulouse
Gynécologie obstétrique, 330 Avenue De Grande Bretagne, 31059, Toulouse Cedex 9
CHU De Saint Etienne
Gynécologie obstétrique, 25 Boulevard Pasteur, 42055, Saint-Etienne Cedex 2

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 2023-01-17 2023-01-18 2025-08-24

Results and documents

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

Documents 46 files

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

TypeTitleVersion
Protocol (for publication) D0_Acta Obstet Gynecol Scand - 2019 - Huisman_2022-501142-30-00 1
Protocol (for publication) D0_Declaration de conformite - sonde 3 voies_2022-501142-30-00 1
Protocol (for publication) D0_Dossier-technique_2022-501142-30-00 1
Protocol (for publication) D0_Fiche information-Sonde Prostatique Silicone 3 voies_2022-501142-30-00 1
Protocol (for publication) D0_Fiche technique sonde_2022-501142-30-00 1
Protocol (for publication) D0_Justification du choix du catheter a ballonnet_2022-501142-30-00 1
Protocol (for publication) D0_Marquage CE_2022-501142-30-00 1
Protocol (for publication) D0_NCT03435458-BigW_2022-501142-30-00 1
Protocol (for publication) D0_Notice utilisation Teleflex_2022-501142-30-00 1
Protocol (for publication) D1_Protocol_2022-501142-30-00 10
Protocol (for publication) D1_protocol-signature_2022-501142-30-00 1
Protocol (for publication) D1_protocol-signature-v2_2022-501142-30-00 2
Protocol (for publication) D1_protocol-signature-v3_2022-501142-30-00 3
Protocol (for publication) D1_protocol-signature-V4_2022-501142-30-00 4
Protocol (for publication) D1_protocol-signature-V7_2022-501142-30-00 7
Protocol (for publication) D1_protocol-synopsis-V3_2022-501142-30-00 3
Protocol (for publication) D1_protocol-tableau-comparatif_2022-501142-30-00 1
Protocol (for publication) D1_Protocol-TC_2022-501142-30-00 10
Protocol (for publication) D1_Protocol-V4-TC_2022-501142-30-00 4
Protocol (for publication) D1_Protocol-V5_2022-501142-30-00 5
Protocol (for publication) D1_Protocol-V5-TC_2022-501142-30-00 5
Protocol (for publication) D1_Protocol-V6-TC_2022-501142-30-00 6
Protocol (for publication) D1_Protocol-V7-TC_2022-501142-30-00 7
Protocol (for publication) D2_protocol-modification_2022-501142-30-00 10
Protocol (for publication) D6_Tab-RECAPITULATIF_2022-501142-30-00 1
Recruitment arrangements (for publication) 2022-501142-30-00_Modalites-Recrutement_V1_20220621_RUBAPRO2 1
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE_V1_202206021_RUBAPRO2 2
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE_V2_20220728_RUBAPRO2 1
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE_V3_202200822_RUBAPRO2 3
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE_V4_20221206_RUBAPRO2 4
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE_V5_20240118_RUBAPRO2 5
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE-2titulaire_V1_20220728_RUBAPRO2 1
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE-2titulaire_V2_20220822_RUBAPRO2 2
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE-2titulaire_V3_20220902_RUBAPRO2 1
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE-2titulaire_V4_20221206_RUBAPRO2 4
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE-2titulaire-clean_V2_20220822_RUBAPRO2 2
Subject information and informed consent form (for publication) 2022-501142-30-00_NICE-clean_V5_20240118_RUBAPRO2 5
Subject information and informed consent form (for publication) 2022-501142-30-00_Questionnaire EXIT version francaise 1
Subject information and informed consent form (for publication) 2022-501142-30-00_tableau-comparatif-NICE_20220822_RUBAPRO2 1
Subject information and informed consent form (for publication) 2022-501142-30-00_tableau-comparatif-NICE_V2_20220728_RUBAPRO2 1
Summary of Product Characteristics (SmPC) (for publication) RCP_Angusta_20210709 1
Summary of Product Characteristics (SmPC) (for publication) RCP_oxytocine_20191120 1
Synopsis of the protocol (for publication) D1_Protocol-synopsis_2022-501142-30-00 9
Synopsis of the protocol (for publication) D1_Protocol-synopsis_EN_2022-501142-30-00 1
Synopsis of the protocol (for publication) D1_Protocol-synopsis_FR_2022-501142-30-00 1
Synopsis of the protocol (for publication) D1_protocol-synopsis-TC_2022-501142-30-00 9

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2022-06-23 France Acceptable
2022-09-14
 2022-09-15
2 SUBSTANTIAL MODIFICATION SM-2 2022-12-16 France Acceptable
2023-02-16
 2023-02-16
3 SUBSTANTIAL MODIFICATION SM-6 2024-01-30 France Acceptable
2024-03-15
 2024-03-15
4 SUBSTANTIAL MODIFICATION SM-7 2024-07-02 France Acceptable
2024-07-29
 2024-07-29
5 SUBSTANTIAL MODIFICATION SM-8 2024-11-18 France Acceptable
2024-12-13
 2024-12-13

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