Induced Vaginal Delivery
Conditions
Brief summary
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.
Interventions
DRUGMifepristone
Mifepristone 200mg taken orally
DRUGMisoprostol
Misoprostol 50 mcg taken orally, and may receive additional doses of misoprostol 50 - 100 mcg as needed
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Uterine Contractions | Up to approximately 72 hours, from start of labor induction to removal of transcervical balloon | Measured total number of uterine contractions per hour - with and without fetal heart rate decelerations. |
| Number of Participants With Uterine Tachysystole | Up to approximately 72 hours from start of labor induction | Participants with uterine tachysystole (more than 5 contractions in 10 minutes with and without fetal heart rate decelerations) . |
| Number of Minutes in Hypertonus | Up to approximately 72 hours, from start of labor induction until the time of delivery | Time in hypertonus (a single contraction lasting more than 2 minutes) per hour. |
| Time to Complete Cervical Dilation | Up to approximately 72 hours from start of labor induction | Total time from start of labor induction to complete cervical dilation (10 cm). |
| 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 | Up to approximately 80 hours after the time of Labor and delivery admission | Total time on Labor & Delivery from the time of admission to the time of transfer to postpartum unit |
| 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 | Up to approximately 72 hours from start of labor induction | Active labor defined as cervical of dilation \>=6 cm. |
| Number of Patients With Severe Maternal Morbidity | Up to approximately 1 week after hospital admission for delivery | Number of participants with serious maternal morbidity based on CDC criteria for major maternal morbidity and mortality |
| Mean Neonatal Arterial Cord Blood pH | Within approximately 2 hours after delivery (approximately 5 minutes to obtain sample) | Laboratory values for neonatal arterial cord blood pH. Arterial pH lower than 7.0 indicates metabolic acidosis. |
| Number of Participants With Neonatal APGAR Score <7 | At 1 minute and 5 minutes of infant life (approximately 10 seconds to perform each assessment) | 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). |
| Number of Patients With Serious Neonatal Morbidity | Up to 7 days after birth | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mifepristone Mifepristone 200 mg orally plus cervical Cook balloon | 15 |
| Misoprostol Misoprostol 50 mcg orally plus cervical Cook balloon | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Spontaneous labor prior to medication administration | 1 | 0 |
Baseline characteristics
| Characteristic | Mifepristone | Misoprostol | Total |
|---|---|---|---|
| Age, Continuous | 30.46 years STANDARD_DEVIATION 4.64 | 31.21 years STANDARD_DEVIATION 7.07 | 30.82 years STANDARD_DEVIATION 5.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 7 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 5 Participants | 7 Participants |
| Region of Enrollment United States | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 1 / 15 | 0 / 15 |
| serious Total, serious adverse events | 3 / 15 | 1 / 15 |
Outcome results
Primary
Mean Neonatal Arterial Cord Blood pH
Laboratory values for neonatal arterial cord blood pH. Arterial pH lower than 7.0 indicates metabolic acidosis.
Time frame: Within approximately 2 hours after delivery (approximately 5 minutes to obtain sample)
Population: Neonatal cords available for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mifepristone | Mean Neonatal Arterial Cord Blood pH | 7.16 pH | Standard Deviation 0.06 |
| Misoprostol | Mean Neonatal Arterial Cord Blood pH | 7.17 pH | Standard Deviation 0.06 |
p-value: 0.9Wilcoxon (Mann-Whitney)
Primary
Number of Minutes in Hypertonus
Time in hypertonus (a single contraction lasting more than 2 minutes) per hour.
Time frame: Up to approximately 72 hours, from start of labor induction until the time of delivery
Population: Intent to treat analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mifepristone | Number of Minutes in Hypertonus | 1.33 minutes | Standard Deviation 5.16 |
| Misoprostol | Number of Minutes in Hypertonus | 0.93 minutes | Standard Deviation 2.49 |
p-value: 0.63Wilcoxon (Mann-Whitney)
Primary
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).
Time frame: At 1 minute and 5 minutes of infant life (approximately 10 seconds to perform each assessment)
Population: Neonates are included in the analysis but were not considered enrolled in the study.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Mifepristone | Number of Participants With Neonatal APGAR Score <7 | 1 minute | 5 Neonates |
| Mifepristone | Number of Participants With Neonatal APGAR Score <7 | 5 minutes | 1 Neonates |
| Misoprostol | Number of Participants With Neonatal APGAR Score <7 | 1 minute | 1 Neonates |
| Misoprostol | Number of Participants With Neonatal APGAR Score <7 | 5 minutes | 0 Neonates |
Comparison: 1 minute APGAR scorep-value: 0.17Fisher Exact
Comparison: APGAR score at 5 minutesp-value: 1Fisher Exact
Primary
Number of Participants With Uterine Tachysystole
Participants with uterine tachysystole (more than 5 contractions in 10 minutes with and without fetal heart rate decelerations) .
Time frame: Up to approximately 72 hours from start of labor induction
Population: Intent to treat analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mifepristone | Number of Participants With Uterine Tachysystole | Uterine tachysystole-12 hours post administration | 0 Participants |
| Mifepristone | Number of Participants With Uterine Tachysystole | Uterine tachysystole- total labor duration | 1 Participants |
| Misoprostol | Number of Participants With Uterine Tachysystole | Uterine tachysystole-12 hours post administration | 5 Participants |
| Misoprostol | Number of Participants With Uterine Tachysystole | Uterine tachysystole- total labor duration | 5 Participants |
Comparison: Comparison of uterine tachysystole of total labor durationp-value: 0.17Fisher Exact
Comparison: Comparison at 12 hours after labor inductionp-value: 0.04Fisher Exact
Primary
Number of Patients Able to Achieve Active Labor
Active labor defined as cervical of dilation \>=6 cm.
Time frame: Up to approximately 72 hours from start of labor induction
Population: Intent to treat analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mifepristone | Number of Patients Able to Achieve Active Labor | 13 Participants |
| Misoprostol | Number of Patients Able to Achieve Active Labor | 13 Participants |
p-value: 1Fisher Exact
Primary
Number of Patients Who Undergo Cesarean Delivery
Time frame: Up to approximately 72 hours from start of labor induction
Population: Intent to treat analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mifepristone | Number of Patients Who Undergo Cesarean Delivery | 5 Participants |
| Misoprostol | Number of Patients Who Undergo Cesarean Delivery | 2 Participants |
p-value: 0.68Fisher Exact
Primary
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
Time frame: Up to 7 days after birth
Population: Neonates are included in the analysis but were not considered enrolled in the study.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Mifepristone | Number of Patients With Serious Neonatal Morbidity | 3 Neonates |
| Misoprostol | Number of Patients With Serious Neonatal Morbidity | 0 Neonates |
p-value: 0.22Fisher Exact
Primary
Number of Patients With Severe Maternal Morbidity
Number of participants with serious maternal morbidity based on CDC criteria for major maternal morbidity and mortality
Time frame: Up to approximately 1 week after hospital admission for delivery
Population: Intent to treat analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mifepristone | Number of Patients With Severe Maternal Morbidity | 0 Participants |
| Misoprostol | Number of Patients With Severe Maternal Morbidity | 1 Participants |
p-value: 1Fisher Exact
Primary
Number of Uterine Contractions
Measured total number of uterine contractions per hour - with and without fetal heart rate decelerations.
Time frame: Up to approximately 72 hours, from start of labor induction to removal of transcervical balloon
Population: Intent to treat analysis set: all participants who were randomized regardless of what treatment (if any) they received.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mifepristone | Number of Uterine Contractions | Total | 103 contractions |
| Mifepristone | Number of Uterine Contractions | Per hour | 9 contractions |
| Misoprostol | Number of Uterine Contractions | Total | 112 contractions |
| Misoprostol | Number of Uterine Contractions | Per hour | 15 contractions |
Comparison: Analysis of total contractionsp-value: 0.44Fisher Exact
Comparison: Analysis of contractions per hourp-value: 0.02Fisher Exact
Primary
Time to Complete Cervical Dilation
Total time from start of labor induction to complete cervical dilation (10 cm).
Time frame: Up to approximately 72 hours from start of labor induction
Population: Intent to treat analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mifepristone | Time to Complete Cervical Dilation | 24.0 hours |
| Misoprostol | Time to Complete Cervical Dilation | 16.0 hours |
p-value: 0.01Wilcoxon (Mann-Whitney)
Primary
Time to Delivery
Time frame: Up to approximately 72 hours, from start of labor induction until the time of delivery
Population: Intent to treat analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mifepristone | Time to Delivery | 26.0 hours |
| Misoprostol | Time to Delivery | 19.0 hours |
Comparison: Comparison at complete cervical dilationp-value: 0.04Wilcoxon (Mann-Whitney)
Primary
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
Time frame: Up to approximately 80 hours after the time of Labor and delivery admission
Population: Intent to treat analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mifepristone | Total Labor and Delivery Unit Admission Duration Time | 29.0 hours |
| Misoprostol | Total Labor and Delivery Unit Admission Duration Time | 21.0 hours |
Comparison: Comparison at postpartum transferp-value: 0.04Wilcoxon (Mann-Whitney)