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

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: Preterm Premature Rupture of Membrane

Treatments: Drug: Placebo of Nifedipine; Drug: Nifedipine

Study type: Interventional

Funder types: Other

Identifiers

NCT03976063

P160917

Details and patient eligibility

About

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.

Full 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.

Enrollment: 850 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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850 participants in 2 patient groups, including a placebo group

Nifedipine

Active Comparator group

Treatment:

Drug: Nifedipine

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo of Nifedipine