Cervical Ripening in Premature Rupture of Membranes

NCT ID: NCT02314728

Last Updated: 2021-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-01
• Study Completion Date: 2016-05-30

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Misoprostol

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Cytotec; Pitocin

Eligibility Criteria

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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Peter S. Bernstein

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kafui Demasio, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Locations

Montefiore Medical Center

The Bronx, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 10472877 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16437525 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16125041 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22105253 (View on PubMed)

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.

Reference Type: RESULT

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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.

Reference Type: RESULT

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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.

Reference Type: RESULT

PMID: 7857439 (View on PubMed)

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.

Reference Type: RESULT

PMID: 1554660 (View on PubMed)

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.

Reference Type: RESULT

PMID: 6717874 (View on PubMed)

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.

Reference Type: RESULT

PMID: 15802392 (View on PubMed)

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.

Reference Type: RESULT

PMID: 9704771 (View on PubMed)

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.

Reference Type: RESULT

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Related Links

https://www.scribd.com/doc/211885423/Practice-Bulletins-No-139-Premature-Rupture-of-Membranes

ACOG Practice Bulletin 139: Premature Rupture of Membranes

https://www.mnhospitals.org/Portals/0/Documents/patientsafety/Perinatal/acog--practice_bulletin_107_2009.pdf

ACOG Practice Bulletin 107: Induction of Labor

Other Identifiers

2014-3462

Identifier Type: -

Identifier Source: org_study_id