Cervical Ripening in Premature Rupture of Membranes

August 9, 2021 updated by: Peter S. Bernstein, Montefiore Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

230

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. All pregnant women diagnosed with PROM without evidence of labor requiring induction
  2. Gestational Age > 34 weeks
  3. Bishop score < 6
  4. Category I Fetal heart rate tracing

Exclusion Criteria:

  1. Contraindication to Induction of Labor
  2. Multiple gestation
  3. Fetal Anomalies
  4. Previous C-Section
  5. HIV Positive Patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Misoprostol
Those randomized to the prostaglandin arm will receive PGE1 (misoprostol) in a dose of 25mcg placed vaginally every 4 hours as per hospital protocol.
Drug: Misoprostol
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.
Other Names:
  • Cytotec
Active Comparator: Oxytocin Alone
Those randomized to the oxytocin arm will receive infusion of oxytocin, which will then be titrated per hospital protocol or until adequate contractions.
Drug: Oxytocin
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 Names:
  • Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Cesarean Section
Time Frame: within 48 hours
Mode of delivery via cesarean section or vaginal delivery
within 48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal and Neonatal Infectious Morbidity
Time Frame: within 72 hours

Maternal infection defined as fever >100.4 on at least two occasions during labor, continued antibiotic treatment on or after PPD#1, histologic confirmation of chorioamnionitis. Dose of Oxytocin, Tachysystole, Estimated blood loss at delivery, maternal length of stay, Epidural use, Indication for cesarean delivery

Neonatal infection defined as WBC <5000 and absolute neutrophil count <1000 or positive blood cultures and neonatal fever, NICU admission, Apgar score less than 7 at 5 minutes,
within 72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Investigators

  • Principal Investigator: Kafui Demasio, MD, MPH, Montefiore Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2014

Primary Completion (Actual)

May 30, 2016

Study Completion (Actual)

May 30, 2016

Study Registration Dates

First Submitted

December 8, 2014

First Submitted That Met QC Criteria

December 10, 2014

First Posted (Estimate)

December 11, 2014

Study Record Updates

Last Update Posted (Actual)

August 10, 2021

Last Update Submitted That Met QC Criteria

August 9, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-3462

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pregnancy

Clinical Trials on Misoprostol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe