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Trial record 90 of 144 for:    NIFEDIPINE

Tocolysis in the Management of Preterm Premature Rupture of Membranes Before 34 Weeks of Gestation (TOCOPROM)

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ClinicalTrials.gov Identifier: NCT03976063
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : October 21, 2019
Sponsor:
Collaborators:
INSERM U1153
Ministry of Health, France
Groupe de Recherche en Obstétrique et Gynécologie
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Preterm Premature Rupture of Membrane Drug: Nifedipine Drug: Placebo of Nifedipine Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 850 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Tocolysis in the Management of Preterm Premature Rupture of Membranes Before 34 Weeks of Gestation: a Double-blinded Randomized Controlled Trial
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tears
Drug Information available for: Nifedipine

Arm Intervention/treatment
Active Comparator: Nifedipine Drug: Nifedipine
Loading dose: Oral Nifedipine 20 mg LP at T0 and T0.5 (i.e. 30 min), total=2x20 mg Maintenance dose: Oral Nifedipine 20 mg LP at T3, then 1 pill every 8 hr for 48 hr (i.e. T11, T19, T27, T35 and T43, total=6x20 mg)

Placebo Comparator: Placebo Drug: Placebo of Nifedipine
Oral Placebo of Nifedipine 20 mg, at T0, T0.5, T3, T11, T19, T27, T35 and T43




Primary Outcome Measures :
  1. Perinatal morti-morbidity [ Time Frame: 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 :
  1. Prolongation of gestation [ Time Frame: Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) ]
    Latency duration (defined as the duration from PPROM to delivery)

  2. Prolongation of gestation [ Time Frame: Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) ]
    Pregnancy prolongation beyond 48 hours after randomization

  3. Prolongation of gestation [ Time Frame: Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) ]
    Pregnancy prolongation beyond 1 week after randomization

  4. Prolongation of gestation [ Time Frame: Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) ]
    Gestational age at delivery

  5. Prolongation of gestation [ Time Frame: Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) ]
    Delivery after 37 weeks of gestation

  6. Maternal morbidity [ Time Frame: During the first 10 days postpartum ]
    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.

  7. Fetal mortality [ Time Frame: Up to delivery so up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy) ]
    Fetal death

  8. Neonatal mortality [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Neonatal death

  9. Neonatal severe morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Mechanical ventilation ≥ 48 hrs

  10. Neonatal severe morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Severe bronchopulmonary dysplasia

  11. Neonatal severe morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Severe intraventricular hemorrhage

  12. Neonatal severe morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Cystic periventricular leucomalacia

  13. Neonatal severe morbidity [ Time Frame: From birth to Day 3 after birth. ]
    Early-onset sepsis

  14. Neonatal severe morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Necrotizing enterocolitis

  15. Neonatal severe morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Retinopathy of prematurity

  16. Neonatal morbidity [ Time Frame: At birth. ]
    Severe fetal acidemia

  17. Neonatal morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Respiratory distress syndrome

  18. Neonatal morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Mild or moderate bronchopulmonary dysplasia

  19. Neonatal morbidity [ Time Frame: From birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Grades I-II intraventricular hemorrhage

  20. Neonatal morbidity [ Time Frame: From Day 3 after birth to discharge from hospital, with a maximum of 24 weeks after birth. ]
    Late-onset sepsis.

  21. Vital status [ Time Frame: At 22-26 months of corrected age ]
    Death between discharge and follow up at 2 years

  22. Frequency of Gross motor impairment among children alive at 2 years of corrected age [ Time Frame: At 22-26 months of corrected age ]
    Cerebral palsy

  23. Frequency of Neurosensory impairment among children alive at 2 years of corrected age [ Time Frame: At 22-26 months of corrected age ]
    Visual impairment

  24. Frequency of Neurosensory impairment among children alive at 2 years of corrected age [ Time Frame: At 22-26 months of corrected age ]
    Hearing impairment



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  • Any tocolytic treatment after PPROM diagnosis, including during in utero transfer
  • 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
  • Coadministration of diltiazem or rifampicine
  • Hypotension (systolic pressure < 90 mmHg)
  • Participation to another interventional study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03976063


Contacts
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Contact: Gilles Kayem, MD, PhD 00 33 1 44 73 51 18 gilles.kayem@aphp.fr
Contact: Nelly Briand, PhD 00 33 1 44 38 18 62 nelly.briand@aphp.fr

Locations
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France
Trousseau University Hospital Recruiting
Paris, France, 75012
Contact: Gilles Kayem, MD, PhD    0033 1 44 73 51 18    gkayem@aphp.fr   
Contact: Clémence Cabanne, RM    0033 1 71 73 86 95    clemencecabanne.tocoprom@gmail.com   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
INSERM U1153
Ministry of Health, France
Groupe de Recherche en Obstétrique et Gynécologie
Investigators
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Principal Investigator: Gilles Kayem, MD, PhD INSERM UMR 1153, Obstetrical, Perinatal and PEdiatric Epidemiology (EPOPé) Research Team, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University, Trousseau University Hospital
Study Director: Elsa Lorthe, RM, PhD INSERM UMR 1153, Obstetrical, Perinatal and PEdiatric Epidemiology (EPOPé) Research Team, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University

Publications:
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03976063     History of Changes
Other Study ID Numbers: P160917
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Preterm premature rupture of membranes
Tocolysis
Nifedipine
Latency
Neonatal outcome
Preterm birth
Randomized controlled trial
Additional relevant MeSH terms:
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Nifedipine
Premature Birth
Fetal Membranes, Premature Rupture
Rupture
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Wounds and Injuries
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Tocolytic Agents
Reproductive Control Agents