PeRinatal Outcomes with ACTive versus expectant management of women with Pre-labor Rupture Of Membranes: a phase III, open-label, randomized controlled multicentric trial

2024-517504-11-00 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 29 Jan 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 17 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 1,400
Countries 1
Sites 17

Pregnant patients diagnosed with premature rupture of membranes (PROM)

The first objective of this study is to evaluate whether active management of women with PROM (early induction) reduces the newborn need of respiratory support.

Key facts

Sponsor
Azienda Ospedaliero Universitaria Di Modena
Participant type
Patients
Age range
18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Trial duration
29 Jan 2025 → ongoing
Decision date (initial)
2025-01-29
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-517504-11-00
EudraCT number
2022-002480-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The first objective of this study is to evaluate whether active management of women with PROM (early induction) reduces the newborn need of respiratory support.

Secondary objectives 1

  1. The secondary objectives of this study are related to the safety of the active management assessed through the rate of stillbirths, the onset of infections in both mother and fetus and the length of hospitalization of the dyads. Moreover, another objective is to reduce the use of antibiotic treatments (ATB) in both mothers and newborns.

Conditions and MedDRA coding

Pregnant patients diagnosed with premature rupture of membranes (PROM)

VersionLevelCodeTermSystem organ class
20.0 PT 10073024 Preterm premature rupture of membranes 100000004868

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1.  Gestational age ≥ 37 weeks  Negative rectovaginal GBS swab  Absent/poor uterine contractile activity 6 h after PROM (0-2 contractions /10 min)  Cephalic presentation  Age ≥18 years of age at the time of randomization  Ability to provide an informed consent  Signed informed consent

Exclusion criteria 1

  1.  Prematurity (<37 weeks)  GBS positive vagino-rectal swab or with an unknown swab  Multiple pregnancies  Previous cesarean section (CS)  Breech presentation, transverse lie or other indication for elective CS  Suspected clinic for intra-amniotic infection (According to the Triple I criteria)  Stained amniotic fluid  Alterations of the FHR  Unknown exact ROM time  Known hypersensitivity to drugs for IOL or their excipients  Presence of unknown vaginal bleeding  Presence of maternal kidney disease (GFR <15 ml/min/1,73 m2).  Every condition contraindicating vaginal delivery

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The need for Neonatal ventilatory support will be evaluated at delivery and include at least one of the following measures:  Free-flowing oxygen in incubator  Low flow oxygen (≤ 2LPM)  High flow oxygen (≥ 3 LPM)  NCPAP or other NIV  Mechanical ventilation

Secondary endpoints 5

  1. Intraamniotic infection is evaluated by the objective measurement of maternal temperature, fetaltachycardia maternal white blood cells > 15000 per mm3, loss of purulent amniotic fluid in labor.
  2. Maternal infection will be evaluated on mothers re-admitted in the hospital until post-partum day 42 because of fever, purulent vaginal discharge or surgical site infection. Length of hospital stay will be recorded as a proxy of maternal/newborn complications. Maternal administration of antibiotics will be reported in terms of doses and quality
  3. Neonatal infection is defined as the yield of a pathogen from blood or CSF coltures. Suspected infection is based on the presence of clinical symptoms and abnormal laboratory markers, i.e. an increase in C reactive proteins above 1.5 mg/dl.
  4. Neonatal pneumonia will be diagnosed in presence of a radiological evidence of persistent consolidation, cavitation or pleural effusion and evidence of worsening gas exchange associated with at least three clinical and/or laboratoristic signs Neonatal administration of antibiotics will be reported in terms of doses and quality
  5. Tachysystole is defined as more of 5 uterine contractions in 10 minutes

Investigational products

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

Test 4

—

SCP107200984 · ATC

Route of administration
INTRAVENOUS USE
Max daily dose
5 IU international unit(s)
Max total dose
5 IU international unit(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
H01BB02 — OXYTOCIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dinoprostone

SUB07195MIG · Substance

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
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Mifepristone

SCP11428287 · ATC

Active substance
Mifepristone
Substance synonyms
RU-486
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
G02AD06 — MISOPROSTOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dinoprostone

SCP130539 · ATC

Active substance
Dinoprostone
Substance synonyms
PGE2, PROSTAGLANDIN E2
Route of administration
VAGINAL USE
Max daily dose
3 mg milligram(s)
Max total dose
3 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
G02AD02 — DINOPROSTONE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

12 Total trials 9 Recruiting 1 Ended
Academic / Non-commercial
Sponsor organisation
Azienda Ospedaliero Universitaria Di Modena
Address
Largo Del Pozzo 71
City
Modena
Postcode
41124
Country
Italy

Scientific contact point

Organisation
Azienda Ospedaliero Universitaria Di Modena
Contact name
Francesca Monari

Public contact point

Organisation
Azienda Ospedaliero Universitaria Di Modena
Contact name
Francesca Monari

Locations

1 EU/EEA country · 17 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Ongoing, recruiting 1,400 17
Rest of world — 0 —

Investigational sites

Italy

17 sites · Ongoing, recruiting
Azienda Unita Sanitaria Locale Della Romagna
Ostetricia-Ginecologia, Viale Giovanni Ghirotti 286, 47521, Cesena
Ospedale Di Sassuolo S.p.A.
Ostetricia e Ginecologia, Via Francesco Ruini 2, 41049, Sassuolo
Azienda Ospedaliera di Padova
Ginecologia e Ostetricia, Via Nicolo' Giustiniani 2, 35128, Padova
Azienda Ospedaliero Universitaria Parma
Ostetricia e Ginecologia, Viale Antonio Gramsci 14, 43126, Parma
Azienda Socio Sanitaria Territoriale Della Brianza
Ostetricia-Ginecologia, Via Santi Cosma E Damiano 10, 20871, Vimercate
Azienda Socio Sanitaria Territoriale Della Brianza
Ginecologia e Ostetricia, Via Santi Cosma E Damiano 10, 20871, Vimercate
ASST Fatebenefratelli Sacco
Ginecologia e Ostetricia, Via Lodovico Castelvetro 32, 20154, Milan
Azienda Ospedaliero Universitaria Di Modena
Ostetricia-Ginecologia, Largo Del Pozzo 71, 41124, Modena
Alessandro Manzoni Hospital
Ostetricia-Ginecologia, Via Dell' Eremo 9, 23900, Lecco
A.O.U. Città della Salute e dalla Scienza di Torino
Ostetricia e Ginecologia, Corso Bramante 88/90, 10126, Torino
Azienda Socio Sanitaria Territoriale Della Brianza
Ostetricia-Ginecologia, Via Santi Cosma E Damiano 10, 20871, Vimercate
Azienda Unita Sanitaria Locale Di Modena
Ginecologia e Ostetricia, Via Guido Molinari 1, 41012, Carpi
IRCCS Istituto Giannina Gaslini
Ostetricia-Ginecologia, Via Gerolamo Gaslini 5, 16147, Genoa
Azienda USL IRCCS Di Reggio Emilia
Ostetricia-Ginecologia, Viale Risorgimento 80, 42123, Reggio Emilia
Azienda Unita Sanitaria Locale Della Romagna
Ostetricia-Ginecologia, Viale Luigi Settembrini 2, 47923, Rimini
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Ostetricia-Ginecologia, Piazzale Spedali Civili 1, 25123, Brescia
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Ostetricia-Ginecologia, Via Francesco Sforza 28, 20122, Milan

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Italy 2025-01-29 2025-01-29

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 2024-517504-11-00 4.1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF Adults 5.0
Subject information and informed consent form (for publication) L1_SIS and ICF Adults placenta 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF Adults_SM-1_track 5.0
Subject information and informed consent form (for publication) L2_Other subject information 3.0
Subject information and informed consent form (for publication) L2_Other subject information_parents_SM-1 1
Subject information and informed consent form (for publication) L2_Other subject information_SM-1_track 3.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC dinoprostone 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC dinoprostone 1 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Misoprostol 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Oxytocin 1
Synopsis of the protocol (for publication) D1_Protocol synopsis IT 2024-517504-11-00 4

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-12-12 Italy Acceptable
2025-01-24
 2025-01-29
2 SUBSTANTIAL MODIFICATION SM-1 2025-11-10 Italy Acceptable 2026-01-19