Mifepristone for Labor Induction

Study Overview
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Brief Summary
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The purpose of this trial is to explore mifepristone as an option for induction of labor at term by evaluating the efficacy of mifepristone use for cervical preparation. Since the Labor Induction versus Expectant Management in Low-Risk Nulliparous Women (ARRIVE) trial supporting that elective induction after 39 weeks decreases cesarean sections and morbidity, rates of elective term inductions are increasing. At Lucile Packard Children's Hospital at Stanford University specifically, approximately 40% of spontaneous vaginal deliveries follow induction of labor, with an average induction time of 20 hours. Previous studies have established the maternal and neonatal safety of mifepristone in term inductions, however, this study will assess the difference in overall time from induction to complete cervical dilation, delivery, and the total time on Labor and Delivery.

Official Title
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Mifepristone as an Adjunct to Transcervical Balloon for Labor Induction (MiLI): A Randomized Clinical Trial

Conditions
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Induced Vaginal Delivery

Intervention / Treatment
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* Drug: Mifepristone
* Drug: Misoprostol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant patients between ages 18 to 45 years Singleton, live gestation Nulliparous Gestational age between 37 weeks 0 days - 42 weeks 0 days Fetus in cephalic presentation Patients admitted for labor induction Patients who are not in labor with intact membranes Patients with no contraindication for vaginal delivery (placenta previa, vasa previa, active genital herpes) Patients with no contraindications for mifepristone (chronic adrenal failure, concurrent long-term corticosteroid therapy, history of allergy to mifepristone, or other prostaglandins, hemorrhagic disorders or concurrent anticoagulant therapy, inherited porphyria, or an intrauterine device (IUD) in place) Patients with a Bishop score <6 at time of randomization Transcervical balloon in place <3 hours prior to the time of randomization without prior cervical preparation Exclusion Criteria: Significant cardiac, renal, or hepatic maternal comorbidities, severe gestational hypertension or preeclampsia with severe features Pregnancies complicated by major fetal anomalies Patients with a uterine scar Pregnancies complicated by fetal growth restriction (Estimated fetal weight <10%) Pregnancies complicated by oligohydramnios Fetuses with an estimated fetal weight >4500 gm by recent ultrasound or Leopold's exam on admission Patients with class 3 obesity (BMI >40) Fetuses with a persistent category 2 or 3 fetal heart tracing at labor induction admission Vaginal bleeding at the time of randomization Any indication for scheduled cesarean delivery Hypersensitivity to oxytocin Uterine contractions equal to or greater than 5 in 10 minutes for sustained 30 minutes Hypersensitivity to prostaglandins

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mifepristone<br>Participants will be given mifepristone with insertion of the cervical Cook balloon for labor induction | Drug: Mifepristone<br>* Mifepristone 200mg taken orally<br>|
| Active Comparator: Misoprostol<br>Participants will be given misoprostol with insertion of the cervical Cook balloon for labor induction | Drug: Misoprostol<br>* Misoprostol 50 mcg taken orally, and may receive additional doses of misoprostol 50 - 100 mcg as needed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of uterine contractions from time of medication administration to removal of the transcervical balloon | Measured total number of uterine contractions per hour - with and without fetal heart rate decelerations from time of medication administration to removal of transcervical balloon | Up to approximately 72 hours after administration of the study medication | 
| Measured number of total minutes of uterine tachysystole or hypertonus per hour from the time of medication administration until the time of delivery | Measured number of total minutes of uterine tachysystole (more than 5 contractions in 10 minutes with and without fetal heart rate decelerations) or hypertonus (a single contraction lasting more than 2 minutes) per hour from the time of medication administration until the time of delivery | Up to approximately 72 hours after administration of study medication | 
| Time from study medication administration to complete cervical dilation | Total time from medication administration to complete cervical dilation (10 cms) | Up to approximately 72 hours after the study medication administration | 
| Time from study medication administration to delivery |  | Up to approximately 72 hours after the study medication has been administered | 
| Total Labor and Delivery unit admission duration time | Total time on Labor & Delivery from the time of admission to the time of transfer to postpartum unit | Up to approximately 80 hours after the time of Labor and delivery admission | 
| Number of patients who undergo cesarean delivery |  | Up to approximately 72 hours after the start of labor induction | 
| Number of patients able to achieve active labor (6 cm) |  | Up to approximately 72 hours after the start of labor induction | 
| Number of patients with severe maternal morbidity | Number of participants with serious maternal morbidity or death based on CDC criteria for major maternal morbidity and mortality | Up to approximately 1 week after hospital admission for delivery | 
| Mean neonatal arterial cord blood pH | Laboratory values for neonatal arterial cord blood pH | Within approximately 2 hours after delivery (approximately 5 minutes to obtain sample) | 
| Mean neonatal APGAR scores from 0-10 | Compare the APGAR scores (at 1 and 5 minutes). The Apgar score comprises five components: 1) color, 2) heart rate, 3) reflexes, 4) muscle tone, and 5) respiration, each of which is given a score of 0, 1, or 2. The score is reported at 1 minute and 5 minutes after birth for all infants, | At 1 minute and 5 minutes of infant life (approximately 10 seconds to perform each assessment) | 
| Number of patients with serious neonatal morbidity | Defined as need for respiratory support within 72 hours after birth, hypoxic-ischemic encephalopathy, seizure, infection, meconium aspiration syndrome, intracranial or subgaleal hemorrhage, hypotension requiring vasopressor support, admission to neonatal intensive care unit | Up to 7 days after birth |