Mifepristone for Labor Induction (MiLI)

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

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.

Study Overview

• Status: Completed
• Conditions: Induced Vaginal Delivery
• Intervention / Treatment: Drug: Mifepristone; Drug: Misoprostol

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pregnant patients between ages 18 to 45 years
2. Singleton, live gestation
3. Nulliparous
4. Gestational age between 37 weeks 0 days - 42 weeks 0 days
5. Fetus in cephalic presentation
6. Patients admitted for labor induction
7. Patients who are not in labor with intact membranes
8. Patients with no contraindication for vaginal delivery (placenta previa, vasa previa, active genital herpes)
9. 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)
10. Patients with a Bishop score <6 at time of randomization
11. Transcervical balloon in place <3 hours prior to the time of randomization without prior cervical preparation

Exclusion Criteria:

1. Significant cardiac, renal, or hepatic maternal comorbidities, severe gestational hypertension or preeclampsia with severe features
2. Pregnancies complicated by major fetal anomalies
3. Patients with a uterine scar
4. Pregnancies complicated by fetal growth restriction (Estimated fetal weight <10%)
5. Pregnancies complicated by oligohydramnios
6. Fetuses with an estimated fetal weight >4500 gm by recent ultrasound or Leopold's exam on admission
7. Patients with class 3 obesity (BMI >40)
8. Fetuses with a persistent category 2 or 3 fetal heart tracing at labor induction admission
9. Vaginal bleeding at the time of randomization
10. Any indication for scheduled cesarean delivery
11. Hypersensitivity to oxytocin
12. Uterine contractions equal to or greater than 5 in 10 minutes for sustained 30 minutes
13. Hypersensitivity to prostaglandins

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Uterine Contractions	Measured total number of uterine contractions per hour - with and without fetal heart rate decelerations.	Up to approximately 72 hours, from start of labor induction to removal of transcervical balloon
Number of Participants With Uterine Tachysystole	Participants with uterine tachysystole (more than 5 contractions in 10 minutes with and without fetal heart rate decelerations) .	Up to approximately 72 hours from start of labor induction
Number of Minutes in Hypertonus	Time in hypertonus (a single contraction lasting more than 2 minutes) per hour.	Up to approximately 72 hours, from start of labor induction until the time of delivery
Time to Complete Cervical Dilation	Total time from start of labor induction to complete cervical dilation (10 cm).	Up to approximately 72 hours from start of labor induction
Time to Delivery		Up to approximately 72 hours, from start of labor induction until the time of delivery
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 from start of labor induction
Number of Patients Able to Achieve Active Labor	Active labor defined as cervical of dilation >=6 cm.	Up to approximately 72 hours from start of labor induction
Number of Patients With Severe Maternal Morbidity	Number of participants with serious maternal morbidity 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. Arterial pH lower than 7.0 indicates metabolic acidosis.	Within approximately 2 hours after delivery (approximately 5 minutes to obtain sample)
Number of Participants With Neonatal APGAR Score <7	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; scores are summed for an overall score of 0 to 10 (higher scores reflect better neonatal outcomes).	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

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Kate Shaw, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Actual): April 29, 2023
• Study Completion (Actual): April 29, 2023

Study Registration Dates

• First Submitted: October 15, 2021
• First Submitted That Met QC Criteria: October 15, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Anti-Ulcer Agents; Contraceptives, Oral, Synthetic; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Misoprostol; Mifepristone
• Other Study ID Numbers: 62448

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