Pregnant women with PPROM at 22 to 33 weeks gestation
Conditions
Interventions
Trade Name: NIFEDIPINE
Pharmaceutical Form: Prolonged-release tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 850 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - PPROM = 24 hrs before diagnosis - Ongoing tocolytic treatment at the time of PPROM - Any tocolytic treatment between PPROM diagnosis and randomization - Fetal condition contraindicating expectant management including chorioamnionitis, intrauterine fetal demise, non-reassuring fetal heart rate at the time of randomization - Cervical dilation > 5 cm - Iatrogenic rupture following amniocentesis (<5 weeks after amniocentesis) - 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 - Coadministration of diltiazem or rifampicine - Hypotension (systolic blood pressure < 90 mmHg) -Participation to another interventional study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to prospectively assess whether short-term (48 hours) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22 to 33 completed weeks’ gestation.;Secondary Objective: To assess the impact of 48 hours tocolysis in cases of PPROM at 22 to 33 weeks’ gestation on prolongation of gestation, maternal morbidity and neonatal minor morbidity. ;Primary end point(s): Primary endpoint The primary composite outcome is based on the most recent published results concerning the prognosis of preterm infants (21,38). It is defined by: - fetal death (in utero fetal death occurring from randomization to birth), - neonatal death up to discharge from hospital (death from birth to discharge, in delivery room or in neonatal intensive care unit [NICU]), - and/or neonatal severe morbidity. Neonatal severe morbidity is defined as any of the following: o mechanical ventilation = 48 hrs, defined as high frequency or conventional mechanical ventilation during at least 48 consecutive hours during the hospitalization (61) o severe bronchopulmonary dysplasia (BPD), defined as requiring oxygen for at least 28 days plus the need for 30% or more oxygen and/or mechanical ventilator support or continuous positive airway pressure at 56 days postnatal age or 36 weeks’ postmenstrual age or discharge, whichever comes first (62) o severe intraventricular hemorrhage (IVH), defined as IVH associated with ventricular dilatation (grade III IVH) and intraparenchymal hemorrhage (i.e., large unilateral parenchymal hyperdensity or large unilateral porencephalic cyst, grade IV IVH); diagnosed by ultrasound (63) o cystic periventricular leucomalacia, periventricular white matter echolucencies at ultrasonography (64) o neonatal early-onset sepsis, diagnosed from positive bacteriology findings in blood or cerebrospinal fluid (confirmed infection) beginning during the first three days of life (65) o necrotizing enterocolitis, stages II and III necrotizing enter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints Maternal and antenatal data will be collected from obstetric files, after women’s discharge from hospital. Prolongation of gestation will be evaluated through different criteria: - Latency duration, defined as the duration from PPROM to delivery - Pregnancy prolongation beyond 48 hours after randomization, - Pregnancy prolongation beyond 1 week after randomization, - Gestational age at delivery, - Delivery after 37 weeks of gestation. Concerning maternal morbidity, we will assess the rates of endometritis in each arm, based on clinical diagnosis associating fever (temperature = 38.0°C) with uterine tenderness, purulent or foul-smelling lochia, and in the absence of any other cause, during the first 10 days postpartum (68). Neonatal data will be collected from neonatal files, after infant’s discharge from hospital. Neonatal morbidity: We will isolate each criteria included in the composite primary outcome and assess its association with tocolysis treatment. We will also study: - Severe fetal acidemia, defined as cord umbilical artery pH less than 7.00 or base deficit greater than 16 mEq/L (16 mmol/L), or both (69) - Respiratory distress syndrome, defined from clinical diagnosis as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with a requirement for supplemental oxygen with a fraction of inspired oxygen of more than 0.21 and a chest radiograph showing hypoaeration and reticulogranular infiltrates - Mild or moderate BPD, defined as requiring oxygen for at least 28 days plus the need for 21% (mild) - 30% (moderate) oxygen at 56 days postnatal age or 36 weeks’ postmenstrual age or discharge, whichever comes first (62) - Grades I-II IVH, defined according to Papile’s classification: subependymal hemorrhage (grade I IVH) or intraventricular hemorrhage without ventricular dilatation (grade II IVH) as diagnosed by ultrasound (63) - Late-onset sepsis, diagnosed | — |
Countries
France
Contacts
Public ContactDRCI Hôpital Saint Louis
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed