Labor Induction With Oral Versus Vaginal Misoprostol

A Cluster Randomized Trial of Labor Induction With Oral Versus Vaginal Misoprostol

This study will compare vaginal and oral misoprostol, to determine whether a vaginal misoprostol regimen achieves a higher vaginal delivery rate in a real-world, high-volume setting, and whether this regimen reduces time and oxytocin need on a high-volume Labor and Delivery unit at Parkland Hospital.

Our primary hypothesis is that among women with singleton, term pregnancies, cervical dilation 2cm or less, and indicated labor induction, the rate of vaginal delivery is significantly increased when a standardized vaginal misoprostol regimen is used, compared with a standardized oral misoprostol regimen.

Study Overview

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

Detailed Description

The purpose of this study is to determine whether the use of a standardized vaginal 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, compared with the currently used oral misoprostol regimen. We also aim to evaluate oxytocin use, time to delivery, uterine activity, indication for cesarean delivery, intrapartum and postpartum infectious morbidities, excess blood loss at delivery, and adverse neonatal outcomes in the overall population as well as nulliparous women specifically.

This will be a prospective, cluster-randomized clinical trial to compare the rate of vaginal delivery achieved when two standards of care are used across a large population of women with indication for labor induction 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 non-reassuring fetal status, 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 vaginal misoprostol regimen (study group) or to oral misoprostol regimen (control group).

According to the randomization protocol each week, participants will be randomized to either the oral misoprostol standard of care (control group) or vaginal misoprostol standard of care (study group). The study group will receive vaginal misoprostol 25 mcg every 3 hours for a maximum of 5 doses in those who meet criteria for prostaglandin administration. The control group will receive oral misoprostol 100 micrograms given every 4 hours for a maximum of 2 doses. Misoprostol will not be administered to patients who have progressed to active labor, defined as 4 centimeters cervical dilation. Intravenous oxytocin will be administered according to current PHHS protocol for both groups.

No direct contact between the research team and patients will be required, as this is a systematic comparison of two standards of care.

The primary outcome will be the rate of vaginal delivery.

Secondary outcomes will include maternal and neonatal outcomes.

Maternal outcomes will include time to delivery, time (hours) of oxytocin, need for oxytocin, indication for cesarean delivery, labor analgesia, clinical chorioamnionitis, tachysystole, hyperstimulation syndrome, excess estimated blood loss, transfusion at delivery, endometritis, surgical site infection, uterine rupture, and unplanned hysterectomy.

Neonatal outcomes will include meconium-stained amniotic fluid, umbilical cord pH <7.0, 5-minute Apgar <4, neonatal intubation or ventilation in the delivery room, neonatal sepsis, and neonatal intensive care (NICU) admission.

• Study Type: Observational
• Enrollment (Actual): 2546
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Study Coordinator, RN; Phone Number: 682-465-8490; Email: lisa.moseley@utsouthwestern.edu
• Study Contact Backup: Name: Emily H Adhikari, MD; Phone Number: 214-648-7825; Email: emily.adhikari@utsouthwestern.edu

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 (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Nulliparous and multiparous pregnant women at 37 weeks gestation or greater, with a living, singleton fetus and no major fetal malformations, in cephalic presentation, no prior uterine scar, with intact fetal membranes, who qualify for prostaglandin administration and who have a cervical dilation of 2 centimeters or less, measured at the level of the internal os, requiring induction at Parkland Health and Hospital System.

Description

Inclusion Criteria:

• Nulliparous and multiparous pregnant women
• 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:

• Non-reassuring fetal status
• Active herpes outbreak
• Prior uterine scar
• Contraindication to prostaglandins according to current Parkland protocol (including 4 or more painful contractions per 10 min prior to prostaglandin administration)
• Contraindication to vaginal delivery

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Vaginal Misoprostol; Patients will receive vaginal misoprostol 25 micrograms given every 3 hours for a maximum of 5 doses. 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
Oral Misoprostol; Patients will receive standard oral misoprostol 100 micrograms given every 4 hours for a maximum of 2 doses 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
Time (hours) of Oxytocin	time (in hours) from start of Oxytocin until turned off for delivery	at delivery
Need for Oxytocin	administration of Oxytocin to facilitate labor contractions	at delivery
Indication for Cesarean Delivery	among women delivered by cesarean, the indication for cesarean	at delivery
Use of Epidural During Labor	use of epidural between the start of induction and delivery	at delivery
Presence of Chorioamnionitis	intrapartum fever (temp greater than or equal to 38 degrees C) with clinical concern for infection and no other identified cause	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 Puerperal Fever and/or Endometritis	maternal fever recorded in the time after delivery, but prior to discharge from the hospital, with or without clinical assessment of endometritis	immediately after delivery to discharge from the hospital, or up to 4 weeks postpartum
Surgical Site Infection	documentation of cellulitis, organisms grown on wound culture, or superficial or deep space surgical site infection with or without purulent drainage requiring readmission	from time of birth until the time of discharge, or up to 4 weeks postpartum
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	immediately after delivery to discharge from the hospital, or up to 4 weeks postpartum
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 or at delivery
Number of Participants with Umbilical pH <7.0	arterial or venous cord blood pH defined as < 7.0	at delivery
Number of Participants with a 5-minute Apgar Score Less Than 4	Appearance, Pulse, Grimace, Activity, Respirations-scored from 0-2 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 <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 the delivery room	at delivery
Number of Participants with Neonatal Sepsis	neonatal bacteremia as defined by bacterial growth in blood cultures	from time of birth until 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
• Investigators: Principal Investigator: Emily H Adhikari, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Actual): September 18, 2022
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; misoprostol; 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 2020-1395

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