Comparison of two prophylactic antibiotic regimens in case of preterm prelabor rupture of membranes before 34 weeks of gestation: a randomized controlled trial

2025-520842-31-00 Protocol APHP230841 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 16 sites · Protocol APHP230841

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 1,008
Countries 1
Sites 16

Population of study participants Pregnant women with PPROM at 22 to 33 weeks’ gestation

To demonstrate the superiority of the association ceftriaxone/azithromycin over the reference association amoxicillin/azithromycin on perinatal morbi-mortality in PPROM at 22 to 33WG.

Key facts

Sponsor
Assistance Publique Hopitaux De Paris
Participant type
Patients
Age range
18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Decision date (initial)
2026-04-28
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Ministère de la Santé

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate the superiority of the association ceftriaxone/azithromycin over the reference association amoxicillin/azithromycin on perinatal morbi-mortality in PPROM at 22 to 33WG.

Secondary objectives 1

  1. To demonstrate the superiority ceftriaxone over the reference association amoxicillin/azithromycin on the length of latency duration and on maternal morbidity and neonatal minor morbidity in PPROM at 22 to 33WG.

Conditions and MedDRA coding

Population of study participants Pregnant women with PPROM at 22 to 33 weeks’ gestation

VersionLevelCodeTermSystem organ class
27.0 LLT 10043505 Threatened abortion antepartum 10036585

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. PPROM between 22 + 0/7 – 33 + 6/7 weeks of gestation, as diagnosed by obstetric team The diagnosis of PPROM is based on the combination of: (1) a suggestive clinical history AND (2) a physical examination (with or without a speculum) confirming discharge OR a positive laboratory test
  2. Eligible to the standard protocol of antibiotic prophylaxis for PPROM in inclusion centre
  3. Singleton gestation
  4. Foetus alive at the time of randomization
  5. 18 years of age or older
  6. French speaking
  7. Affiliated to any French social security regime or equivalent system
  8. Informed consent signed

Exclusion criteria 9

  1. Clinically suspected intra-uterine infection at the time of PPROM diagnosis (defined by association of PPROM AND fever (≥ 38°) AND at least two of the following signs: fetal tachycardia > 160 beats/min for 10 minutes, uterine pain or spontaneous labor, purulent amniotic fluid at the cervical os)
  2. Ongoing antibiotic treatment (≥ 24h) by amoxicillin, 3CG or a macrolide at the time of inclusion (other antibiotics are not cause for exclusion)
  3. Major foetal abnormality
  4. Maternal allergy or contra-indication to any antibiotic(s) used in the randomised trial protocol
  5. Current participation in another interventional study involving a drug
  6. A mental state that prevents understanding of the trial and the ability to give free and informed consent
  7. Persons deprived of their liberty by administrative or judicial order
  8. Persons under guardianship or conservatorship
  9. Person who is a relative of the investigator whom enrolled them in the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Composite outcome including foetal death and/or neonatal death AND/OR neonatal severe morbidity (defined by ≥ 1 of the following: mechanical ventilation 48hrs, severe bronchopulmonary dysplasia, severe intraventricular haemorrhage, white matter injury, neonatal early-onset sepsis, neonatal late-onset sepsis, necrotizing enterocolitis, retinopathy of prematurity).

Secondary endpoints 3

  1. Pregnancy duration
  2. Maternal infectious morbidity
  3. Neonatal mild or moderate morbidity: 1. Prevalence of maternal or neonatal colonization/infection with ESBL- or 3rd generation cephalosporin-resistant- enterobacteria ; 2. Psycho-motor development at the age of 2 years by parental auto-questionnaire

Investigational products

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

Test 1

Ceftriaxone

SUB07431MIG · Substance

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

Comparator 2

Amoxicillin

SUB05481MIG · Substance

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

Azithromycin

SUB05660MIG · Substance

Active substance
Azithromycin
Pharmaceutical form
TABLET
Route of administration
ORAL USE
Max daily dose
500 mg milligram(s)
Max total dose
1500 mg milligram(s)
Max treatment duration
5 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

Assistance Publique Hopitaux De Paris

251 Total trials 131 Recruiting 54 Ended
Academic / Non-commercial
Sponsor organisation
Assistance Publique Hopitaux De Paris
Address
Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City
Paris Cedex 10
Postcode
75475
Country
France

Scientific contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Investigateur Coordonnateur

Public contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Investigateur Coordonnateur

Locations

1 EU/EEA country · 16 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 1,008 16
Rest of world — 0 —

Investigational sites

France

16 sites · Authorised, recruitment pending
Hopital Louis Mourier
Gynécologie Obstétrique, 178 Rue des Renouillers, 92700, Colombes
Centre Hospitalier Universitaire De Rennes
Gynécologie Obstétrique, 16 Boulevard De Bulgarie, Bp 90349, Rennes
Centre Hospitalier Universitaire De Toulouse
Gynécologie Obstétrique, 330 Avenue De Grande Bretagne, 31059, Toulouse Cedex 9
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Gynécologie Obstétrique, 185 Rue Raymond Losserand, 75014, Paris
Trousseau Hospital
Gynécologie Obstétrique, 26 Avenue Du Docteur Arnold Netter, 75012, Paris
CHRU De Nancy
Gynécologie Obstétrique, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Hôpital Universitaire Necker Enfants Malades - AP-HP
Gynécologie Obstétrique, 149 rue de Sèvres, 75015, Paris
Centre Hospitalier Universitaire De Bordeaux
Gynécologie Obstétrique, Place Amelie Raba Leon, 33000, Bordeaux
CHU Saint Etienne Hôpital Nord
Gynécologie Obstétrique, Av. Albert Raimond, 42055, Saint Etienne
Les Hopitaux Universitaires De Strasbourg
Gynécologie Obstétrique, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Hôpitaux Universitaires Paris Centre-Hôpital Cochin
Gynécologie Obstétrique, 123 Boulevard de Port-Royal, Batiment Copernic,, Paris
Assistance Publique Hopitaux De Paris
Gynécologie Obstétrique, Avenue Du 14 Juillet, 93140, Bondy
Robert Debre University Hospital
Gynécologie Obstétrique, 48 Boulevard Serurier, 75019, Paris
Hôpital Bicêtre -APHP
Gynécologie Obstétrique, 78 Rue du Général Leclerc, 94270, Le Kremlin-Bicêtre
Centre Hospitalier Universitaire De Caen Normandie
Gynécologie Obstétrique, Avenue De La Cote De Nacre, 14000, Caen
Hopital Antoine-Beclere
Gynécologie Obstétrique, 157 Rue De La Porte De Trivaux, 92140, Clamart

Results and documents

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

Documents 12 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2025-520842-31-00 1-3
Recruitment arrangements (for publication) K1__DocumentAdditionnel_2025-520842-31-00 1
Recruitment arrangements (for publication) K2_RecruitmentProcedure_2025-520842-31-00 1
Subject information and informed consent form (for publication) L1_NIFC_Autorite Parentale 2025-520842-31-00 1-2
Subject information and informed consent form (for publication) L1_NIFC_Majeur 2025-520842-31-00 1-3
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_AMOXICILLINE 1 g 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_AZITHROMYCINE 250 mg 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_CEFTRIAXONE 1g IM 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_CEFTRIAXONE 1g IV 1
Synopsis of the protocol (for publication) D1_Synopsis_EN_2025-520842-31-00 1-3
Synopsis of the protocol (for publication) D1_Synopsis_FR_2025-520842-31-00 1-3
Synopsis of the protocol (for publication) D4_Questionnaire_2ans_2025-520842-31-00 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2026-01-09 France Acceptable
2026-04-24
 2026-04-28

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