Cervical Ripening in Premature Rupture of Membranes
Condition: Pregnancy; Premature Rupture of Membranes; Preterm Premature Rupture of Membranes; Unfavorable Cervix
MeSH terms: Premature Birth; Fetal Membranes, Premature Rupture; Rupture
Study type: Interventional

Summary: 
      Premature rupture of membranes (PROM) is diagnosed by demonstrating amniotic fluid in the
      vaginal canal before the onset of labor. The integrity of the amniotic membrane is
      compromised thereby increasing the risk of intrauterine infection and compression of the
      umbilical cord. PROM complicates 3% to 8% of pregnancies in the US and is responsible for 30%
      of preterm births. Intrauterine infection remains the most significant maternal and neonatal
      sequelae associated with PROM and this risk increases with the length of time from ruptured
      membrane to delivery. Induction of labor has been shown to reduce the rates of
      chorioamnionitis, endometritis and NICU admissions4. Specifically, induction of labor with
      prostaglandin agents followed by oxytocin, versus oxytocin alone has been shown to be
      effective for labor induction resulting in vaginal delivery. Management strategies for PROM
      have been controversial, and published studies on outcomes are over one to two decades old,
      which does not account for changes in clinical trends and practice patterns. Recently ACOG
      recommends that patients presenting at 37 weeks gestation or greater with PROM should be
      induced if not in labor, and "generally with oxytocin". In women with PROM without the onset
      of labor, the cervix is commonly unfavorable and induction with oxytocin alone may lead to an
      increased risk of cesarean section. With a c-section rate as high as 33%, women undergoing
      induction of labor have an increased risk of c-section and its associated morbidity and long
      term sequela. ACOG's recommendation for the use of oxytocin as the induction agent may be
      meant to avoid a theoretical increased risk of chorioamnionitis in this patient population
      however it does not take into account the status of the cervix, which may result in a
      increased risk of c-section. The purpose of the proposed study is to determine whether
      cervical ripening in women with PROM and an unfavorable cervix is associated with increase
      rates of vaginal delivery and decreased cesarean section rate compared to induction of labor
      with oxytocin alone. The investigators aim to determine the incidence of endometritis, and
      neonatal infection associated with PROM in the current medical environment of antibiotic
      prophylaxis and antenatal steroid use, taking into account the changes in patient
      characteristics.
    

Detailed description: 
      We will perform a prospective randomized control trial involving women with singleton
      gestation at ≥ 34 weeks gestation who require an induction of labor after diagnosis of PROM
      with an unfavorable cervix. PROM will be diagnosed and confirmed with sterile speculum
      examination demonstrating pooling and/or positive ferning or nitrazine. Cervical status will
      be assessed by visual exam, digital exam or transvaginal ultrasound to assign a Bishop score
      (dilation, effacement, station, consistency & position). Determination of patient eligibility
      will be based on the clinical exam and confirmation of PROM. Upon diagnosis, if the patient
      meets inclusion criteria and accepts to participate in the study, they will be consented by
      the study investigator and then be randomized to prostaglandin followed by oxytocin or
      oxytocin alone group. Allocation concealment will be performed via the utilization of
      pre-sequentially numbered, manila sealed envelopes stapled closed.

      There are two treatment groups and will be analyzed on an intent-to-treat basis.
      Randomization will be performed using a computer generated simple randomization sequence.
      Data safety monitoring will be instituted (see data safety monitoring plan below). Once
      randomization is completed, the labor and delivery providers will be informed of the
      treatment arm and this will be placed on the chart. Those randomized to the prostaglandin arm
      will receive PGE1 (misoprostol) in a dose of 25mcg placed vaginally every 4 hours as per
      hospital protocol. Those randomized to the oxytocin arm will receive infusion of oxytocin,
      which will then be titrated per hospital protocol until adequate contractions. Further
      management after the start of the respective arm will be based on clinical judgment of the
      provider.
    

Intervention name(s): Misoprostol; Oxytocin
Intervention type(s): Drug; Drug
Intervention description(s): Patients who are randomized to receive misoprostol will have 25mcg placed vaginally. Repeated dosing of misoprostol is based on clinical exam and clinical judgment of the provider.; Patients who are randomized to receive oxytocin alone will receive intravenous administration of oxytocin as designated by the hospital protocol. Protocol begins with 2 milliunits of oxytocin that is then titrated over time. Titration is based on clinical exam and clinical judgment of the provider and is continued until there are adequate uterine contractions.
Other intervention name(s): Cytotec; Pitocin
Intervention MeSH terms: Misoprostol; Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Bishop Score; Induction of Labor; Cervical Ripening; Unfavorable Cervix; Mode of Delivery; C-Section; Cesarean Section; Misoprostol; Prostaglandin; Prostaglandin E1