Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
850
Countries
1
Sites
29
obstetric_pathological delivery
To assess whether short-term (48 hr) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22 to 33 completed weeks’ gestation.
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]
- Trial duration
- 25 Jul 2024 → ongoing
- Decision date (initial)
- 2024-07-25
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Ministère de la Santé
External identifiers
- EU CT number
- 2024-512872-36-00
- EudraCT number
- 2018-004482-14
- ClinicalTrials.gov
- NCT03976063
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
To assess whether short-term (48 hr) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22 to 33 completed weeks’ gestation.
Secondary objectives 1
- To assess the impact of 48 hours tocolysis in cases of PPROM at 22 to 33 weeks’ gestation on latency duration, maternal morbidity and neonatal minor morbidity.
Conditions and MedDRA coding
obstetric_pathological delivery
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- - 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. - Singleton gestation - Fetus alive at the time of randomization - 18 years of age or older - French speaking - Affiliated to social security or an equivalent system - Informed consent and signed
Exclusion criteria 1
- - PPROM ≥ 24 hrs before diagnosis - Ongoing tocolytic treatment at the time of PPROM - Tocolytic treatment with Nifedipine between PPROM diagnosis and randomization - 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 - Cervical dilation ≥ 5 cm - Iatrogenic rupture caused by amniocentesis or trophoblast biopsy - Major fetal anomaly - Maternal allergy or contra-indication to Nifedipine or placebo drug components: - Myocardial infarction - Unstable angina pectoris - Hepatic insufficiency - Cardiovascular shock - Beta blockers - Cardiopathy - Co-administration of diltiazem, rifampicine, transdermal nitrates or any antihypertensive medication - Hypotension (systolic blood pressure < 90 mmHg) - Participation to another interventional research (category 1) in which intervention could interfere with Tocoprom’s results (efficacy and safety).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is a composite outcome including fetal death, neonatal death up to discharge from hospital and/or neonatal severe morbidity.
Secondary endpoints 1
- Prolongation of gestation - Maternal morbidity - Neonatal minor morbidity - Outcomes at 2 years of corrected age
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB09253MIG · Substance
- Active substance
- Nifedipine
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 160 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
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Assistance Publique Hopitaux De Paris
- 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
- Pr Gilles KAYEM
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr Gilles KAYEM
Locations
1 EU/EEA country · 29 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 850 | 29 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
gynecology, 43 Boulevard De L Hopital, 75013, Paris
Assistance Publique Hopitaux De Paris
gynecology, 4 Rue De La Chine, 75020, Paris
Centre Hospitalier Intercommunal Creteil
gynecology, 40 Avenue De Verdun, 94000, Creteil
Centre Hospitalier Universitaire De Lille
gynecology, Avenue Eugene Avinee, 59037, Lille Cedex
Centre Hospitalier Universitaire De Bordeaux
Gynecology, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier General De St Denis
gynecology, 2 Rue Du Docteur Delafontaine, Bp 279, St Denis Cedex
Centre Hospitalier Regional D'Angers
gynecology, 4 Rue Larrey, 49100, Angers
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Gynecology, 185 Rue Raymond Losserand, 75674, Paris Cedex 14
Centre Hospitalier De Valenciennes
gynecology, 114 Avenue Desandrouin, 59300, Valenciennes
University Hospital Of Clermont-Ferrand
Gynecology, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Assistance Publique Hopitaux De Paris
gynecology, 78 Rue Du General Leclerc, 94270, Le Kremlin-Bicetre
Centre Hospitalier Regional De Marseille
gynecology, 265 Chemin Des Bourrely, 13015, Marseille
Assistance Publique Hopitaux De Paris
gynecology, 157 Rue De La Porte De Trivaux, 92140, Clamart
Centre Hospitalier Universitaire De Caen Normandie
gynecology, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Centre Hospitalier Intercommunal De Poissy Saint Germain
gynecology, Residence Les Maisonnees, 10 Rue Du Champ Gaillard, Poissy
Centre Hospitalier Regional De Marseille
gynecology, 147 Boulevard Baille, 13005, Marseille
Assistance Publique Hopitaux De Paris
gynecology, 26 Avenue Du Docteur Arnold Netter, 75012, Paris
Hopital NOVO
Gynecology-obstetric, 6 Avenue De L Ile De France, 95300, Pontoise
Assistance Publique Hopitaux De Paris
gynecology, 27 Rue Du Faubourg Saint Jacques, 75014, Paris
Centre Hospitalier De Pau
gynecology, 4 Boulevard Hauterive, 64000, Pau
Assistance Publique Hopitaux De Paris
gynecology, Avenue Du 14 Juillet, 93140, Bondy
Centre Hospitalier Universitaire De Saint Etienne
gynecology, St Priest En Jarez, 25 Boulevard Pasteur, St Etienne Cedex 2
Hopital Louis Mourier
Gynécologie Obstétrique, 178 Rue des Renouillers, 92700, Colombes
Centre Hospitalier Universitaire De Nantes
gynecology, 38 Boulevard Jean Monnet, 44000, Nantes
Centre Hospitalier Universitaire Rouen
gyneecology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Hopital Saint Joseph
gynecology, 26 Boulevard De Louvain, 13008, Marseille
Centre Hospitalier Regional Universitaire De Tours
Gynecology, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Les Hopitaux Universitaires De Strasbourg
gynecology, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
CHRU De Nancy
Gynecology-obstetric, 11 Rue Du Morvan, Bp 80001, Vandoeuvre Les Nancy Cedex
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-07-25 | 2024-07-25 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-512872-36-00 | 10-2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Recruitment arrangements (for publication) | K1_recruitment-arrangements | 1 |
| Subject information and informed consent form (for publication) | L2 _carte-anniv2ans | 1-0 |
| Subject information and informed consent form (for publication) | L2_ Courrier-parental_suivi 5ans | 1-1 |
| Subject information and informed consent form (for publication) | L2_Other subject information Patient Card 2024-512872-36-00 | 1-0 |
| Subject information and informed consent form (for publication) | SIS and ICF adult | 2-0 |
| Subject information and informed consent form (for publication) | SIS and ICF parental authorities | 1-0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Nifedipine | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EN 2024-512872-36-00 | 10-2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis FR 24-512872-36-00 | 10-2 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-10 | France | Acceptable 2024-07-16
|
2024-07-25 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-10-15 | France | Acceptable | 2024-11-13 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-09-09 | France | Acceptable 2025-10-28
|
2025-10-29 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-02-23 | France | Acceptable | 2026-03-13 |