Foley Bulb With Oral Misoprostol for Induction of Labor

Foley Bulb With Oral Misoprostol Versus Oral Misoprostol for Induction of Labor: A Cluster Randomized Trial

Induction of labor is associated with increased cesarean delivery rates, particularly in women with an unfavorable cervix. Both pharmacologic and mechanical methods are utilized for cervical ripening and labor induction. Evidence on the safety and effectiveness of various mechanical and pharmacologic methods of cervical ripening and labor induction is abundant, and yet the majority of clinical trials evaluate time to delivery, rather than mode of delivery. This is a prospective, cluster-randomized clinical trial to compare a standard method of induction at our institution (oral misoprostol) with an alternative, commonly used combination method of oral misoprostol and transcervical foley bulb in women with term pregnancies requiring induction of labor.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Labor, Induced
• Intervention / Treatment: Other: Foley bulb plus Oral Misoprostol; Other: Oral Misoprostol

Detailed Description

The purpose of this study is to determine whether the use of a transcervical foley catheter, in combination with the standard oral misoprostol regimen will result in a decreased primary cesarean delivery rate among women with a cervical dilation of 2 centimeters of less who require induction of labor at term. This study is not an FDA-regulated study: there is no intent to test the foley bulb under an FDA-regulated protocol. Likewise, there is no intent to submit the results of this study for a change in the labeling of the foley used for this study. This study was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center, and by the Office of Research Administration at Parkland Health and Hospital System.

This will be a prospective, cluster-randomized trial comparing two accepted methods of induction of labor at term among women who present for delivery at Parkland Hospital. Eligible participants will include nulliparous and multiparous women at 37 weeks gestation or greater, with a living, singleton fetus and no major fetal malformations, in cephalic presentation, with intact membranes, no prior uterine scar, who qualify for prostaglandin administration and who have a cervical dilation of 2 centimeters or less, measured at the level of the internal os. Patients with latex allergy, non-reassuring fetal status, HIV, active herpes outbreak, a prior uterine scar, or any contraindication to prostaglandins (including 4 or more painful contractions per 10 minutes prior to prostaglandin administration) will be excluded from participation in the study.

Computer-generated cluster randomization will occur on a weekly basis for all study participants, to either the combination method of foley bulb plus oral misoprostol regimen (study group) or to oral misoprostol alone regimen (control).

According to the randomization protocol each week, participants will be randomized to either the standard of care (oral misoprostol/control group) or standard of care plus foley bulb (study group). The study group will undergo placement of a 30 French foley catheter filled with 30-35cc sterile saline into the cervix in addition to the standard regimen of oral misoprostol 100 micrograms given every 4 hours for a maximum of 2 doses, for patients who meet criteria for fetal well-being, and do not had more than 4 painful contractions in 10 minutes. Misoprostol will not be administered to patients who have progressed to active labor, defined as 4 centimeters cervical dilation. The control group will undergo induction with our current standard oral misoprostol protocol alone, administered as 100 micrograms given every 4 hours for a maximum of 2 doses. Both groups will receive oxytocin as indicated by current labor protocols at our institution.

The primary outcome will be the rate of vaginal delivery. Secondary outcomes will include obstetric outcomes, maternal outcomes, and neonatal outcomes. Obstetric outcomes will include indication for induction, need for oxytocin, indication for cesarean delivery, time to active labor, time to delivery, labor analgesia, presence of chorioamnionitis, meconium-stained amniotic fluid, terbutaline use, tachysystole (defined as 6 or more contractions in 10 minutes or tetanic contraction of 120 seconds or longer) or hyperstimulation syndrome (defined as tachysystole accompanied by fetal heart rate decelerations). Maternal outcomes will include estimated blood loss, transfusion requirement, postpartum fever, uterine rupture, and unplanned hysterectomy. Neonatal outcomes will include umbilical cord blood pH, 5-minute APGAR score, intubation or ventilation in the delivery room, neonatal sepsis, and admission to Neonatal Intensive Care Unit (NICU) admission.

• Study Type: Interventional
• Enrollment (Actual): 2227
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Health and Hospital Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 37 weeks gestation or greater
• Living, singleton fetus
• No major fetal malformations
• Cephalic presentation
• No prior uterine scar
• Intact fetal membranes
• Qualifies for prostaglandin administration according to current Parkland protocol
• Have a cervical dilation of 2 centimeters or less, measured at the level of the internal os
• Have an indication for induction or attempted induction of labor according to Parkland protocol

Exclusion Criteria:

• latex allergy
• non-reassuring fetal status
• HIV
• active herpes outbreak
• Prior uterine scar
• Contraindication to prostaglandins according to current Parkland protocol
• Contraindication to vaginal delivery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Foley bulb plus Oral Misoprostol; Patients will received initial transcervical foley bulb, followed by oral misoprostol 100 micrograms given every 4 hours for a maximum of 2 doses.	Other: Foley bulb plus Oral Misoprostol; Although labeled "experimental" for comparison purposes, this is not an experimental intervention, as the method is a currently accepted standard of care for cervical ripening and labor induction in the United States.
ACTIVE_COMPARATOR: Oral Misoprostol; Patients will receive oral misoprostol 100 micrograms given every 4 hours for a maximum of 2 doses.	Other: Oral Misoprostol; Patients will receive standard oral misoprostol 100mcg according to current Labor Induction Protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Vaginal Delivery	vaginal delivery at first induction	at delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Delivery	Time (in hours) from start of induction agent to delivery at first induction	from start of induction agent to time of delivery
Indication for Cesarean Delivery	Among women delivered by cesarean, the indication for cesarean	at delivery
Dose of Oxytocin Given (mcg or mg)	Total dose of oxytocin given for induction as calculated by volume infused, concentration of solution and rate of infusion	at delivery
Time With Foley Bulb in Place	time (in hours) from insertion to removal or expulsion of foley bulb	From time of documented insertion until the time of documented expulsion or removal, whichever came first, assessed up to 24 hours.
Presence of Chorioamnionitis	Intrapartum fever (temp equal or greater than 38C) with no other identified cause	at delivery
Use of Intravenous Analgesia During Labor	Intravenous analgesia used between the start of induction and delivery	at delivery
Number of Participants Used Neuraxial Analgesia During Labor	Regional or neuraxial analgesia (labor epidural or spinal) used between the start of induction and delivery	from start of induction to delivery
Number of Participants Used General Anesthesia for Delivery	General anesthesia administered for delivery	at delivery
Number of Participants With Meconium-stained Amniotic Fluid	Identification of any meconium (green tinge) in the amniotic fluid before or during delivery by a healthcare provider's assessment of gross fluid color.	At the time of rupture of membranes and at delivery
Terbutaline Use	Administration of terbutaline, a tocolytic agent, for tetanic contractions with or without fetal heart rate decelerations	at delivery
Number of Participants With Tachysystole	6 or more contractions in 10 minutes or tetanic contraction of 120 seconds or longer	at delivery
Number of Participants With Uterine Hyperstimulation Syndrome	Tachysystole accompanied by fetal heart rate decelerations	at delivery
Number of Participants With Excess Blood Loss	Maternal excess blood loss is defined as >500ml for vaginal and >1000ml for cesarean delivery	at delivery
Number of Participants With Blood Transfusion	administration of blood products related to delivery blood loss	at delivery
Number of Participants With Uterine Rupture	spontaneous separation of myometrium in a previously intact, unscarred uterus	at delivery
Number of Participants With Unplanned Hysterectomy	unplanned removal of the uterus following delivery of the fetus	at discharge from the hospital following delivery
Number of Participants With Postpartum Fever	Fever recorded in the time after delivery but prior to discharge from the hospital, with clinical assessment of endometritis	Following delivery and prior to discharge
Number of Participants With Umbilical Cord Blood pH <7.0	Arterial or venous cord blood pH defined as <7.0	at delivery
Number of Participants With an 5-minute Apgar Score Less Than 4	Appearance, Pulse, Grimace, Activity, Respirations - scored from 0 to 2 for each component, added to make a total score and used as an assessment of initial response to newborn resuscitation, lower scores associated with poor outcomes. Here defined as Apgar less than 4 at 5 minutes.	5 minutes after time of birth
Number of Participants That Needed Mechanical Ventilation in Delivery Room (Yes/No)	Intubation with mechanical support or control of neonatal breathing in delivery room	at delivery
Number of Participants Administered Neonatal Antibiotics and/or Neonatal Blood Cultures	Administration of neonatal antibiotics and/or neonatal blood cultures	From time of birth until the time of discharge or up to 7 days of life, whichever comes first.
Number of Participants With Neonatal Sepsis	Neonatal bacteremia as defined by bacterial growth in blood cultures	From time of birth until the time of discharge or up to 7 days of life, whichever comes first.
Number of Participants With NICU Admission Order	Admission order to neonatal intensive care unit (NICU) placed between the time of delivery and infant discharge	From time of birth until the time of discharge or up to 7 days of life, whichever comes first.

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• Adhikari EH, Nelson DB, McIntire DD, Leveno KJ. Foley Bulb Added to an Oral Misoprostol Induction Protocol: A Cluster Randomized Trial. Obstet Gynecol. 2020 Nov;136(5):953-961. doi: 10.1097/AOG.0000000000004123.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ACTUAL): May 13, 2019
• Study Completion (ACTUAL): May 13, 2019

Study Registration Dates

• First Submitted: December 28, 2017
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (ACTUAL): January 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2020
• Last Update Submitted That Met QC Criteria: October 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Pregnancy; Cervical Ripening; Labor Induction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: STU 092016-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes