Cervical Ripening in Premature Rupture of Membranes

NCT02314728 | Completed Results DMC

• 1 other identifier: 2014-3462
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pregnancy; Premature Rupture of Membranes; Preterm Premature Rupture of Membranes; Unfavorable Cervix

Keywords

Bishop Score; Induction of Labor; Cervical Ripening; Unfavorable Cervix; Mode of Delivery; C-Section; Cesarean Section; Misoprostol; Prostaglandin; Prostaglandin E1

Outcome Measures

Primary Outcomes (1)

• Rate of Cesarean Section

  Mode of delivery via cesarean section or vaginal delivery

  within 48 hours

Secondary Outcomes (1)

• Maternal and Neonatal Infectious Morbidity

  within 72 hours

Study Arms (2)

Misoprostol

ACTIVE COMPARATOR

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

Oxytocin Alone

ACTIVE COMPARATOR

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

Interventions

Misoprostol DRUG

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.

Also known as: Cytotec

Misoprostol

Oxytocin DRUG

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.

Also known as: Pitocin

Oxytocin Alone

Eligibility Criteria

• Age: 15 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All pregnant women diagnosed with PROM without evidence of labor requiring induction
• Gestational Age \> 34 weeks
• Bishop score \< 6
• Category I Fetal heart rate tracing

You may not qualify if:

• Contraindication to Induction of Labor
• Multiple gestation
• Fetal Anomalies
• Previous C-Section
• HIV Positive Patients

Sponsors & Collaborators

• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (12)

• Merrill DC, Zlatnik FJ. Randomized, double-masked comparison of oxytocin dosage in induction and augmentation of labor. Obstet Gynecol. 1999 Sep;94(3):455-63. doi: 10.1016/s0029-7844(99)00338-5.

  PMID: 10472877 RESULT

• Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005302. doi: 10.1002/14651858.CD005302.pub2.

  PMID: 16437525 RESULT

• Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin North Am. 2005 Sep;32(3):411-28. doi: 10.1016/j.ogc.2005.03.003.

  PMID: 16125041 RESULT

• Kunze M, Hart JE, Lynch AM, Gibbs RS. Intrapartum management of premature rupture of membranes: effect on cesarean delivery rate. Obstet Gynecol. 2011 Dec;118(6):1247-1254. doi: 10.1097/AOG.0b013e3182351b0c.

  PMID: 22105253 RESULT

• Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL, Wang EE, Weston JA, Willan AR. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. N Engl J Med. 1996 Apr 18;334(16):1005-10. doi: 10.1056/NEJM199604183341601.

  PMID: 8598837 RESULT

• Balci O, Mahmoud AS, Acar A, Colakoglu MC. Comparison of induction of labor with vaginal misoprostol plus oxytocin versus oxytocin alone in term primigravidae. J Matern Fetal Neonatal Med. 2011 Sep;24(9):1084-7. doi: 10.3109/14767058.2010.531798. Epub 2010 Nov 19.

  PMID: 21087166 RESULT

• Gonen R, Samberg I, Degani S. Intracervical prostaglandin E2 for induction of labor in patients with premature rupture of membranes and an unripe cervix. Am J Perinatol. 1994 Nov;11(6):436-8. doi: 10.1055/s-2007-994615.

  PMID: 7857439 RESULT

• Mahmood TA, Dick MJ, Smith NC, Templeton AA. Role of prostaglandin in the management of prelabour rupture of the membranes at term. Br J Obstet Gynaecol. 1992 Feb;99(2):112-7. doi: 10.1111/j.1471-0528.1992.tb14466.x.

  PMID: 1554660 RESULT

• Duff P, Huff RW, Gibbs RS. Management of premature rupture of membranes and unfavorable cervix in term pregnancy. Obstet Gynecol. 1984 May;63(5):697-702.

  PMID: 6717874 RESULT

• Vrouenraets FP, Roumen FJ, Dehing CJ, van den Akker ES, Aarts MJ, Scheve EJ. Bishop score and risk of cesarean delivery after induction of labor in nulliparous women. Obstet Gynecol. 2005 Apr;105(4):690-7. doi: 10.1097/01.AOG.0000152338.76759.38.

  PMID: 15802392 RESULT

• Wing DA, Paul RH. Induction of labor with misoprostol for premature rupture of membranes beyond thirty-six weeks' gestation. Am J Obstet Gynecol. 1998 Jul;179(1):94-9. doi: 10.1016/s0002-9378(98)70256-x.

  PMID: 9704771 RESULT

• Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013 Dec 2;2013(12):CD001058. doi: 10.1002/14651858.CD001058.pub3.

  PMID: 24297389 RESULT

Related Links

• ACOG Practice Bulletin 139: Premature Rupture of Membranes
• ACOG Practice Bulletin 107: Induction of Labor

MeSH Terms

Conditions

Fetal Membranes, Premature Rupture; Preterm Premature Rupture of the Membranes

Interventions

Misoprostol; Oxytocin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

1. Protocol breech 2. Variability in provider practices on labor and delivery. Reluctance to use misoprostol with rupture membranes. 3. Patient wait times impacted compliance with protocol. They went into labor while awaiting for a labor bed.

Results Point of Contact

• Title: Kafui A. Demasio, MD, MPH, Maternal Fetal Medicine, Dept of Obstetrics/Gynecology and Women's Health
• Organization: Montefiore Medical Center

kdemasio@montefiore.org

718-920-2767

Study Officials

• Kafui Demasio, MD, MPH

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 11, 2014
• Study Start: October 1, 2014
• Primary Completion: May 30, 2016
• Study Completion: May 30, 2016
• Last Updated: August 10, 2021
• Results First Posted: August 10, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)