Clinical trial NCT04755218: Labor Induction With Oral Versus Vaginal Misoprostol
Official title: A Cluster Randomized Trial of Labor Induction With Oral Versus Vaginal Misoprostol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy
Labor, Induced
Keywords: Pregnancy
Labor induction
Cervical Ripening
misoprostol
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2021-02-16
Enrollment: 2546
Sex: FEMALE
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Vaginal Delivery
timeFrame: at delivery
Secondary outcomes:
measure: Time to Delivery
timeFrame: from start of induction agent to time of delivery
measure: Time (hours) of Oxytocin
timeFrame: at delivery
measure: Need for Oxytocin
timeFrame: at delivery
measure: Indication for Cesarean Delivery
timeFrame: at delivery
measure: Use of Epidural During Labor
timeFrame: at delivery
measure: Presence of Chorioamnionitis
timeFrame: at delivery
measure: Number of Participants with Uterine Hyperstimulation Syndrome
timeFrame: at delivery
measure: Number of Participants with Excess Blood Loss
timeFrame: at delivery
measure: Number of Participants with Blood Transfusion
timeFrame: at delivery
measure: Number of Participants with Puerperal Fever and/or Endometritis
timeFrame: immediately after delivery to discharge from the hospital, or up to 4 weeks postpartum
measure: Surgical Site Infection
timeFrame: from time of birth until the time of discharge, or up to 4 weeks postpartum
measure: Number of Participants with Uterine Rupture
timeFrame: at delivery
measure: Number of Participants with Unplanned Hysterectomy
timeFrame: immediately after delivery to discharge from the hospital, or up to 4 weeks postpartum
measure: Number of Participants with Meconium-Stained Amniotic Fluid
timeFrame: at the time of rupture of membranes or at delivery
measure: Number of Participants with Umbilical pH <7.0
timeFrame: at delivery
measure: Number of Participants with a 5-minute Apgar Score Less Than 4
timeFrame: 5 minutes after time of birth
measure: Number of Participants That Needed Mechanical Ventilation in Delivery Room (Yes/No)
timeFrame: at delivery
measure: Number of Participants with Neonatal Sepsis
timeFrame: from time of birth until time of discharge or up to 7 days of life, whichever comes first
measure: Number of Participants with NICU Admission Order
timeFrame: from time of birth until the time of discharge or up to 7 days of life, whichever comes first.
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Parkland Health and Hospital Systems
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Emily H Adhikari, MD
role: PRINCIPAL_INVESTIGATOR
References: