Tocolysis in the Management of Preterm Premature Rupture of Membranes Before 34 Weeks of Gestation
- Conditions
- Preterm Premature Rupture of Membrane
- Interventions
- Registration Number
- NCT03976063
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
The purpose of this study is to assess whether short-term (48 hr) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22 to 33 completed weeks' gestation.
- Detailed Description
Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and accounts for one-third of preterm births. It is a leading cause of neonatal mortality and morbidity and increases the risk of maternal infectious morbidity. In cases of early PPROM (22 to 33 completed weeks' gestation), expectant management is recommended in the absence of labor, chorioamnionitis or fetal distress. Antenatal steroids and antibiotics administration are recommended by international guidelines. However, there is no recommendation regarding tocolysis administration in the setting of PPROM. In theory, reducing uterine contractility should delay delivery and reduce risks of prematurity and neonatal adverse consequences. Likewise, a prolongation of gestation may allow administering a corticosteroids complete course that is associated with a two-fold reduction of morbidity and mortality. However, tocolysis may prolong fetal exposure to inflammation and be associated with higher risk of materno-fetal infection, potentially associated with neonatal death or long-term sequelae, including cerebral palsy.
The purpose of this study is to assess whether short-term (48 hr) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22 to 33 completed weeks' gestation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 850
- Preterm premature rupture of membranes (PPROM) between 220/7 - 336/7 weeks of gestation, as diagnosed by obstetric team
- Singleton gestation
- Fetus alive at the time of randomization (reassuring fetal heart monitoring)
- 18 years of age or older
- French speaking
- Affiliated to social security regime or an equivalent system
- Informed consent and signed
-
PPROM ≥ 24 hours 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, 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
placebo drug components: lactose monohydrate, colloidal silica, microcrystalline cellulose
- Coadministration of diltiazem or rifampicin
- Hypotension (systolic pressure < 90 mmHg)
- Participation to another interventional research (category 1) in which intervention could interfere with TOCOPROM's results (efficacy and safety)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo of Nifedipine - Nifedipine Nifedipine -
- Primary Outcome Measures
Name Time Method Perinatal morti-morbidity Up to discharge from hospital, with a maximum of 24 weeks after birth. Composite outcome including fetal death, neonatal death and/or neonatal severe morbidity (mechanical ventilation ≥ 48 hrs, severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, cystic periventricular leucomalacia, neonatal early-onset sepsis, necrotizing enterocolitis, retinopathy of prematurity).
- Secondary Outcome Measures
Name Time Method Prolongation of gestation Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) Delivery after 37 weeks of gestation
Neonatal mortality From birth to discharge from hospital, with a maximum of 24 weeks after birth. Neonatal death
Frequency of Gross motor impairment among children alive at 2 years of corrected age At 22-26 months of corrected age Cerebral palsy
Maternal morbidity At delivery Intra-uterine infection, defined as fever (maternal temperature ≥38 °C), with no alternative cause identified, associated with at least two of the following criteria: persistent fetal tachycardia \> 160 bpm, uterine pain or painful uterine contractions or spontaneous labor, purulent amniotic fluid.
Fetal mortality Up to delivery so up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) Fetal death
Neonatal severe morbidity From birth to discharge from hospital, with a maximum of 24 weeks after birth. Retinopathy of prematurity
Frequency of Neurosensory impairment among children alive at 2 years of corrected age At 22-26 months of corrected age Hearing impairment
Neonatal morbidity From Day 3 after birth to discharge from hospital, with a maximum of 24 weeks after birth. Late-onset sepsis.
Vital status At 22-26 months of corrected age Death between discharge and follow up at 2 years
Trial Locations
- Locations (1)
Trousseau University Hospital
🇫🇷Paris, France