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

NCT03976063 | Active Not Recruiting Phase 3

• 1 other identifier: P160917
• Study Type: interventional
• Target: 857
• Locations: 1 country
• Sites: 1

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.

Conditions

Preterm Premature Rupture of Membrane

Keywords

Preterm premature rupture of membranes; Tocolysis; Nifedipine; Latency; Neonatal outcome; Preterm birth; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• Prolongation of gestation

  Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy)

• Prolongation of gestation

  Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy)

• Prolongation of gestation

  Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy)

• Prolongation of gestation

  Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy)

• Prolongation of gestation

  Up to 20 weeks after PPROM (i.e. up to the maximum duration of a normal pregnancy)

Study Arms (2)

Nifedipine

ACTIVE COMPARATOR

Drug: Nifedipine

Placebo

PLACEBO COMPARATOR

Drug: Placebo of Nifedipine

Interventions

Nifedipine DRUG

Loading dose: Oral Nifedipine 20 mg prolonged-release at T0 and T0.5 (i.e. 30 min), total=2x20 mg Maintenance dose: Oral Nifedipine 20 mg prolonged-release at T3, then 1 pill every 8 hr for 48 hr (i.e. T11, T19, T27, T35 and T43, total=6x20 mg)

Nifedipine

Placebo of Nifedipine DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• years of age or older
• French speaking
• Affiliated to social security regime or an equivalent system
• Informed consent and signed

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Ministry of Health, France: collaborator
• Groupe de Recherche en Obstétrique et Gynécologie: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Trousseau University Hospital

Paris, 75012, France

Location

Related Publications (7)

• 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;2014(2):CD007062. doi: 10.1002/14651858.CD007062.pub3.

  PMID: 24578236 BACKGROUND

• 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.

  PMID: 28412086 BACKGROUND

• 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.

  PMID: 23182704 BACKGROUND

• 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.

  PMID: 30870741 BACKGROUND

• 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.

  PMID: 24901312 BACKGROUND

• Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.

  PMID: 35947046 DERIVED

• Lorthe E, Kayem G; TOCOPROM Study Group and the GROG (Groupe de Recherche en Obstetrique et Gynecologie). Tocolysis in the management of preterm prelabor rupture of membranes at 22-33 weeks of gestation: study protocol for a multicenter, double-blind, randomized controlled trial comparing nifedipine with placebo (TOCOPROM). BMC Pregnancy Childbirth. 2021 Sep 8;21(1):614. doi: 10.1186/s12884-021-04047-2.

  PMID: 34496799 DERIVED

MeSH Terms

Conditions

Preterm Premature Rupture of the Membranes; Premature Birth

Interventions

Nifedipine

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: June 5, 2019
• Study Start: October 7, 2019
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2031
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

FR (1)