Preterm Premature Rupture of Membrane Clinical Trial
— TOCOPROMOfficial title:
Tocolysis in the Management of Preterm Premature Rupture of Membranes Before 34 Weeks of Gestation: a Double-blinded Randomized Controlled Trial
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.
Status | Recruiting |
Enrollment | 850 |
Est. completion date | November 2030 |
Est. primary completion date | November 2025 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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) |
Country | Name | City | State |
---|---|---|---|
France | Trousseau University Hospital | Paris |
Lead Sponsor | Collaborator |
---|---|
Assistance Publique - Hôpitaux de Paris | Groupe de Recherche en Obstétrique et Gynécologie, INSERM U1153, Ministry of Health, France |
France,
Couteau C, Haumonte JB, Bretelle F, Capelle M, D'Ercole C. [Management of preterm and prelabour rupture of membranes in France]. J Gynecol Obstet Biol Reprod (Paris). 2013 Feb;42(1):21-8. doi: 10.1016/j.jgyn.2012.10.008. Epub 2012 Nov 24. French. — View Citation
Flenady V, Wojcieszek AM, Papatsonis DN, Stock OM, Murray L, Jardine LA, Carbonne B. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database Syst Rev. 2014 Jun 5;2014(6):CD002255. doi: 10.1002/14651858.CD002255.pub2. — View Citation
Lorthe E, Goffinet F, Marret S, Vayssiere C, Flamant C, Quere M, Benhammou V, Ancel PY, Kayem G. Tocolysis after preterm premature rupture of membranes and neonatal outcome: a propensity-score analysis. Am J Obstet Gynecol. 2017 Aug;217(2):212.e1-212.e12. doi: 10.1016/j.ajog.2017.04.015. Epub 2017 Apr 13. — View Citation
Mackeen AD, Seibel-Seamon J, Muhammad J, Baxter JK, Berghella V. Tocolytics for preterm premature rupture of membranes. Cochrane Database Syst Rev. 2014 Feb 27;(2):CD007062. doi: 10.1002/14651858.CD007062.pub3. — View Citation
Schmitz T, Sentilhes L, Lorthe E, Gallot D, Madar H, Doret-Dion M, Beucher G, Charlier C, Cazanave C, Delorme P, Garabedian C, Azria E, Tessier V, Senat MV, Kayem G. Preterm premature rupture of the membranes: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol. 2019 May;236:1-6. doi: 10.1016/j.ejogrb.2019.02.021. Epub 2019 Mar 2. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Perinatal morti-morbidity | 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). | Up to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Prolongation of gestation | Latency duration (defined as the duration from PPROM to delivery) | Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) | |
Secondary | Prolongation of gestation | Pregnancy prolongation beyond 48 hours after randomization | Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) | |
Secondary | Prolongation of gestation | Pregnancy prolongation beyond 1 week after randomization | Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) | |
Secondary | Prolongation of gestation | Gestational age at delivery | Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) | |
Secondary | Prolongation of gestation | Delivery after 37 weeks of gestation | Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) | |
Secondary | Maternal morbidity | Endometritis, 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 | |
Secondary | Maternal morbidity | 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. | At delivery | |
Secondary | Fetal mortality | Fetal death | Up to delivery so up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) | |
Secondary | Neonatal mortality | Neonatal death | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal severe morbidity | Mechanical ventilation = 48 hrs | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal severe morbidity | Severe bronchopulmonary dysplasia | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal severe morbidity | Severe intraventricular hemorrhage | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal severe morbidity | Cystic periventricular leucomalacia | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal severe morbidity | Early-onset sepsis | From birth to Day 3 after birth. | |
Secondary | Neonatal severe morbidity | Necrotizing enterocolitis | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal severe morbidity | Retinopathy of prematurity | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal morbidity | Severe fetal acidemia | At birth. | |
Secondary | Neonatal morbidity | Respiratory distress syndrome | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal morbidity | Mild or moderate bronchopulmonary dysplasia | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal morbidity | Grades I-II intraventricular hemorrhage | From birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Neonatal morbidity | Late-onset sepsis. | From Day 3 after birth to discharge from hospital, with a maximum of 24 weeks after birth. | |
Secondary | Vital status | Death between discharge and follow up at 2 years | At 22-26 months of corrected age | |
Secondary | Frequency of Gross motor impairment among children alive at 2 years of corrected age | Cerebral palsy | At 22-26 months of corrected age | |
Secondary | Frequency of Neurosensory impairment among children alive at 2 years of corrected age | Visual impairment | At 22-26 months of corrected age | |
Secondary | Frequency of Neurosensory impairment among children alive at 2 years of corrected age | Hearing impairment | At 22-26 months of corrected age |
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