Clinical trial • Phase III • Other

NIFEDIPINE for Preterm premature rupture of membranes (PPROM)

Phase III trial of NIFEDIPINE for Preterm premature rupture of membranes (PPROM).

Overview

Trial Therapeutic Area
Other
Trial Disease
Preterm premature rupture of membranes (PPROM)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
10-06-2024
First CTIS Authorization Date
25-07-2024

Trial design

Randomised, placebo of nifedipine (placebo comparator); dose and schedule not specified in available ctis data-controlled Phase III trial in France.

Randomised
Yes
Comparator
Placebo of Nifedipine (placebo comparator); dose and schedule not specified in available CTIS data
Target Sample Size
850
Trial Duration For Participant
730

Eligibility

Recruits 850 Pregnant women are included (participants must be 18 years or older and French speaking). Informed consent must be signed by the adult participant. Neonates/children are involved for outcome assessment at 2 years of corrected age; subject information and informed consent forms for adults and parental authorities documents are provided (SIS and ICF adult; SIS and ICF parental authorities; parental follow-up documents), indicating parental/guardian consent procedures for child follow-up..

Pregnancy Exclusion
- Fetal condition contraindicating expectant management including chorioamnionitis, placental abruption, haemorrhagic placenta praevia, intrauterine fetal demise, non-reassuring fetal heart rate at the time of randomization
Vulnerable Population
Pregnant women are included (participants must be 18 years or older and French speaking). Informed consent must be signed by the adult participant. Neonates/children are involved for outcome assessment at 2 years of corrected age; subject information and informed consent forms for adults and parental authorities documents are provided (SIS and ICF adult; SIS and ICF parental authorities; parental follow-up documents), indicating parental/guardian consent procedures for child follow-up.

Inclusion criteria

  • {"criterion_text":"- Preterm premature rupture of membranes (PPROM) between 22 0/7 - 33 6/7 weeks of gestation, as diagnosed by obstetric teams: the diagnosis is usually based on 2 positive criteria from maternal history, sterile speculum examination to confirm fluid leakage from the cervical canal and performance of a diagnostic test."}
  • {"criterion_text":"- Singleton gestation"}
  • {"criterion_text":"- Fetus alive at the time of randomization"}
  • {"criterion_text":"- 18 years of age or older"}
  • {"criterion_text":"- French speaking"}
  • {"criterion_text":"- Affiliated to social security or an equivalent system"}
  • {"criterion_text":"- Informed consent and signed"}

Exclusion criteria

  • {"criterion_text":"- PPROM ≥ 24 hrs before diagnosis"}
  • {"criterion_text":"- Ongoing tocolytic treatment at the time of PPROM"}
  • {"criterion_text":"- Tocolytic treatment with Nifedipine between PPROM diagnosis and randomization"}
  • {"criterion_text":"- Fetal condition contraindicating expectant management including chorioamnionitis, placental abruption, haemorrhagic placenta praevia, intrauterine fetal demise, non-reassuring fetal heart rate at the time of randomization"}
  • {"criterion_text":"- Cervical dilation ≥ 5 cm"}
  • {"criterion_text":"- Iatrogenic rupture caused by amniocentesis or trophoblast biopsy"}
  • {"criterion_text":"- Major fetal anomaly"}
  • {"criterion_text":"- Maternal allergy or contra-indication to Nifedipine or placebo drug components:"}
  • {"criterion_text":"- Myocardial infarction"}
  • {"criterion_text":"- Unstable angina pectoris"}
  • {"criterion_text":"- Hepatic insufficiency"}
  • {"criterion_text":"- Cardiovascular shock"}
  • {"criterion_text":"- Beta blockers"}
  • {"criterion_text":"- Cardiopathy"}
  • {"criterion_text":"- Co-administration of diltiazem, rifampicine, transdermal nitrates or any antihypertensive medication"}
  • {"criterion_text":"- Hypotension (systolic blood pressure < 90 mmHg)"}
  • {"criterion_text":"- Participation to another interventional research (category 1) in which intervention could interfere with Tocoprom’s results (efficacy and safety)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is a composite outcome including fetal death, neonatal death up to discharge from hospital and/or neonatal severe morbidity.","definition_or_measurement_approach":"Composite outcome including fetal death, neonatal death up to discharge from hospital and/or neonatal severe morbidity (as stated in the protocol)."}

Secondary endpoints

  • {"endpoint_text":"- Prolongation of gestation","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Maternal morbidity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Neonatal minor morbidity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Outcomes at 2 years of corrected age","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
850
Recruitment Window Months
147
Consent Approach
Adult participants (pregnant women) must be 18 years or older, French speaking, and provide signed informed consent. Subject information and informed consent forms for adults are provided (SIS and ICF adult). Parental authorities / parental consent documents are provided for child-related follow-up (SIS and ICF parental authorities, and follow-up parental communications for outcomes at 2 years).

Geography

Total Number Of Sites
29
Total Number Of Participants
850

France

Earliest CTIS Part Ii Submission Date
10-07-2024
Latest Decision Or Authorization Date
13-03-2026
Processing Time Days
611
Number Of Sites
29
Number Of Participants
850

Sites

Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Gynecology
Principal Investigator Name
Loïc Sentilhes
Principal Investigator Email
loic.sentilhes@chu-bordeaux.fr
Contact Person Name
Loïc Sentilhes
Contact Person Email
loic.sentilhes@chu-bordeaux.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
gynecology
Principal Investigator Name
Florence Bretelle
Principal Investigator Email
Florence.BRETELLE@ap-hm.fr
Contact Person Name
Florence Bretelle
Contact Person Email
Florence.BRETELLE@ap-hm.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
gyneecology
Principal Investigator Name
Eric Verspyck
Principal Investigator Email
Eric.Verspyck@chu-rouen.fr
Contact Person Name
Eric Verspyck
Contact Person Email
Eric.Verspyck@chu-rouen.fr
Site Name
Centre Hospitalier General De St Denis
Department Name
gynecology
Principal Investigator Name
Mireille Ruiz
Principal Investigator Email
mireille.ruiz@ch-stdenis.fr
Contact Person Name
Mireille Ruiz
Contact Person Email
mireille.ruiz@ch-stdenis.fr
Site Name
CHRU De Nancy
Department Name
Gynecology-obstetric
Principal Investigator Name
Olivier Morel
Principal Investigator Email
olivier.morel@chru-nancy.fr
Contact Person Name
Olivier Morel
Contact Person Email
olivier.morel@chru-nancy.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
gynecology
Principal Investigator Name
Norbert Winer
Principal Investigator Email
norbert.winer@chu-nantes.fr
Contact Person Name
Norbert Winer
Contact Person Email
norbert.winer@chu-nantes.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Gynecology
Principal Investigator Name
Franck Perrotin
Principal Investigator Email
Franck.Perrotin@med.univ-tours.fr
Contact Person Name
Franck Perrotin
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Gynecology
Principal Investigator Name
Matthieu Chamagne
Principal Investigator Email
matthieu.chamagne@aphp.fr
Contact Person Name
Matthieu Chamagne
Contact Person Email
matthieu.chamagne@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
gynecology
Principal Investigator Name
Anne Gaël Cordier
Principal Investigator Email
anne-gael.cordier@aphp.fr
Contact Person Name
Anne Gaël Cordier
Contact Person Email
anne-gael.cordier@aphp.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
gynecology
Principal Investigator Name
Roxane Gibert
Principal Investigator Email
roxane.gibert@chu-lille.fr
Contact Person Name
Roxane Gibert
Contact Person Email
roxane.gibert@chu-lille.fr
Site Name
Hopital Saint Joseph
Department Name
gynecology
Principal Investigator Name
Raoul Desbriere
Principal Investigator Email
rdesbriere@hopital-saint-joseph.fr
Contact Person Name
Raoul Desbriere
Site Name
Centre Hospitalier De Valenciennes
Department Name
gynecology
Principal Investigator Name
Nadia Tillouche
Principal Investigator Email
tillouche-n@valenciennes.fr
Contact Person Name
Nadia Tillouche
Contact Person Email
tillouche-n@valenciennes.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
gynecology
Principal Investigator Name
Aude Girault
Principal Investigator Email
aude.girault@aphp.fr
Contact Person Name
Aude Girault
Contact Person Email
aude.girault@aphp.fr
Site Name
Centre Hospitalier De Pau
Department Name
gynecology
Principal Investigator Name
Caroline Bohec
Principal Investigator Email
bohecc@ch-pau.fr
Contact Person Name
Caroline Bohec
Contact Person Email
bohecc@ch-pau.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
gynecology
Principal Investigator Name
Alexandra Benachi
Principal Investigator Email
lexandra.benachi@abc.aphp.fr
Contact Person Name
Alexandra Benachi
Contact Person Email
lexandra.benachi@abc.aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
gynecology
Principal Investigator Name
Dominique Luton
Principal Investigator Email
dominique.luton@aphp.fr
Contact Person Name
Dominique Luton
Contact Person Email
dominique.luton@aphp.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
gynecology
Principal Investigator Name
Chris Minella
Principal Investigator Email
chris.minella@chru-strasbourg.fr
Contact Person Name
Chris Minella
Site Name
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Department Name
Gynecology
Principal Investigator Name
Elie Azria
Principal Investigator Email
eazria@hpsj.fr
Contact Person Name
Elie Azria
Contact Person Email
eazria@hpsj.fr
Site Name
Hopital NOVO
Department Name
Gynecology-obstetric
Principal Investigator Name
Christophe Poncelet
Principal Investigator Email
christophe.poncelet@ch-pontoise.fr
Contact Person Name
Christophe Poncelet
Site Name
Hopital Louis Mourier
Department Name
Gynécologie Obstétrique
Principal Investigator Name
Charles Egloff
Principal Investigator Email
charles.egloff@aphp.fr
Contact Person Name
Charles Egloff
Contact Person Email
charles.egloff@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
gynecology
Principal Investigator Name
Gilles Kayem
Principal Investigator Email
gilles.kayem@aphp.fr
Contact Person Name
Gilles Kayem
Contact Person Email
gilles.kayem@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
gynecology
Principal Investigator Name
Julievirginie Blanc
Principal Investigator Email
julievirginie.blanc@ap-hm.fr
Contact Person Name
Julievirginie Blanc
Contact Person Email
julievirginie.blanc@ap-hm.fr
Site Name
Centre Hospitalier Intercommunal De Poissy Saint Germain
Department Name
gynecology
Principal Investigator Name
Paul Berveiller
Principal Investigator Email
paul.berveiller@uvsq.fr
Contact Person Name
Paul Berveiller
Contact Person Email
paul.berveiller@uvsq.fr
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
gynecology
Principal Investigator Name
Celine Chauleur
Principal Investigator Email
celine.chauleur@chu-st-etienne.fr
Contact Person Name
Celine Chauleur
Site Name
Centre Hospitalier Intercommunal Creteil
Department Name
gynecology
Principal Investigator Name
Edouard Lecarpentier
Principal Investigator Email
edouard.lecarpentier@chicreteil.fr
Contact Person Name
Edouard Lecarpentier
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Gynecology
Principal Investigator Name
Denis Gallot
Principal Investigator Email
dgallot@chu-clermontferrand.fr
Contact Person Name
Denis Gallot
Contact Person Email
dgallot@chu-clermontferrand.fr
Site Name
Centre Hospitalier Regional D'Angers
Department Name
gynecology
Principal Investigator Name
Véronique Beaudoux
Principal Investigator Email
veronique.beaudoux@chu-angers.fr
Contact Person Name
Véronique Beaudoux
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
gynecology
Principal Investigator Name
Michel Dreyfus
Principal Investigator Email
dreyfus-m@chu-caen.fr
Contact Person Name
Michel Dreyfus
Contact Person Email
dreyfus-m@chu-caen.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
gynecology
Principal Investigator Name
Amélie Benbara
Principal Investigator Email
amelie.benbara@aphp.fr
Contact Person Name
Amélie Benbara
Contact Person Email
amelie.benbara@aphp.fr

Sponsor

Primary sponsor

Full Name
Assistance Publique Hopitaux De Paris
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Third parties

  • {"country":"","full_name":"Ministère de la Santé","duties_or_roles":"Source of monetary support / funding","organisation_type":""}

Investigational products

Investigational Product Name
NIFEDIPINE
Active Substance
NIFEDIPINE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Has MIA numbers: N° 2023_195_1_2 (UNITHER DEVELOPPEMENT BORDEAUX) and N° 2023_200_1_2_3_10 (EPHP-AGEPS)
Maximum Dose
Max daily dose 100 mg; max total dose 160 mg (as provided in CTIS data)
Investigational Product Name
Placebo of Nifedipine
Modality
Other
Authorisation Status
MIA numbers listed at product/group level: N° 2023_195_1_2 (UNITHER DEVELOPPEMENT BORDEAUX) and N° 2023_200_1_2_3_10 (EPHP-AGEPS)

Related trials

Other published trials that may interest you.