A Comparison of Oral Misoprostol and Vaginal Misoprostol for Cervical Ripening and Induction of Labor

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02777190

Enrollment

Registered

2016-05-19

Start date

2017-11-01

Completion date

2019-04-23

Last updated

2022-10-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Labor; Forced or Induced, Affecting Fetus or Newborn, Pregnancy

Keywords

misoprostol, cytotec, cervical ripening, labor, induced, active labor

Brief summary

The purpose of this study is to study if misoprostol administered orally is at least as effective as misoprostol administered vaginally for cervical ripening and the induction of labor. The main purpose is to show that oral misoprostol administration is non-inferior to vaginal misoprostol administration with respect to the time interval from misoprostol administration to onset of active phase of labor. The study is a non-inferiority, prospective randomized controlled trial comparing oral misoprostol given as 25 mcg every 2 hours versus vaginal misoprostol given as 25 mcg every 4 hours.

Interventions

DRUGMisoprostol

Comparing dosing of misoprostol 25 mcg orally every 2 hours versus 25 mcg vaginally every 4 hours.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

1. Pregnant Female Patients greater than or equal to 18 years of age 2. Induction of labor for a single live intrauterine pregnancy 3. Greater than or equal to 37 weeks gestational age 4. Cephalic presentation 5. 20 minute reassuring fetal heart rate (reactive nonstress test (NST)) 6. Bishop score based on sterile vaginal exam of less than or equal to 6, for which the cervical dilation is less than or equal to 2 cm. 7. Equal to 3 or less uterine contractions over 10 minutes

Exclusion criteria

1. Previous uterine scar 2. Contraindication to vaginal delivery 3. Patients with preeclampsia 4. Grand multiparty - greater than or equal to 5 live births or stillbirths 5. Premature rupture of membranes 6. Suspected intrauterine growth restriction 7. Fetal anomalies 8. Contraindication to misoprostol (history of allergy to prostaglandins, glaucoma)

Design outcomes

Primary

Measure	Time frame	Description
Time to Active Labor	from start of induction of labor (first misoprostol administration) to active phase of labor, up to 3 days.	Active phase of labor defined as greater than or equal to 6 cm cervical dilation

Secondary

Measure	Time frame	Description
Time to Vaginal Delivery	from start of induction of labor (first misoprostol administration) to vaginal delivery, up to 3 days	includes vaginal deliveries only; cesarean section deliveries are excluded
Cesarean Section Rate	From enrollment until delivery, up to 3 days	Number of cesarean sections/total deliveries (%)
Rate of Tachysystole	from enrollment until delivery, up to 3 days	Tachysystole is defined as 4 or more contractions in a 10 minute period.
Rate of Tachysystole Causing Non-reassuring Fetal Heart Tones	From enrollment until delivery, up to 3 days	Previously defined as hyperstimulation, this outcome measure is defined as 4 or more contractions in a 10 minute period (tachysystole) thought to be causing recurrent variable or late decelerations, bradycardia, or minimal variability in the fetal heart rate tracing (non-reassuring fetal heart tones,which would require intervention to resolve or delivery of the infant).
Rate of Need for Tocolysis	from enrollment until delivery, up to 3 days	Tocolysis is the administration of medication to decrease or stop contractions.
Time to Initiation of Oxytocin for Labor Augmentation	From start of induction of labor (first misoprostol administration) to initiation of oxytocin for labor augmentation, up to 36 hours	The length of time (in hours) between the administration of misoprostol (first dose) and the first administration of oxytocin for labor augmentation.
Rate of Meconium Stained Fluid	from enrollment until delivery, up to 3 days	Amniotic fluid with visible meconium (from fetal defecation) within it.
Neonatal Morbidity	4 hours from delivery	binary composite outcome defined as Apgar score \< 7, or cord blood gas pH of less than 7 or base deficit great than 12, or neonatal intensive care unit admission within 4 hours of delivery.
Rate of Anti-emetic Use	from enrollment until delivery, up to 3 days	Use of medication to treat nausea.
Rate of Vaginal Delivery Within 24 Hours	24 hours from start of induction of labor (first misoprostol administration)	Vaginal delivery within from start of induction with misoprostol.
Rate of Abandoning Misoprostol for Cervical Ripening and Switching to Mechanical Dilation for Cervical Ripening	from enrollment until delivery, up to 3 days	Based on clinician's judgment on the progress of the induction, the rate that misoprostol administration was stopped and a cervical ripening balloon was used instead
Rate of Chorioamnionitis	from enrollment until delivery, up to 3 days	Chorioamnionitis is defined as an intraamniotic infection.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Oral Misoprostol oral misoprostol given 25 mcg every 2 hours	17
Vaginal Misoprostol vaginal misoprostol given 25 mcg every 4 hours	17
Total	34

Baseline characteristics

Characteristic	Vaginal Misoprostol	Total	Oral Misoprostol
Age, Continuous	26.5 years STANDARD_DEVIATION 5.7	27.2 years STANDARD_DEVIATION 5	27.8 years STANDARD_DEVIATION 4.3
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	1 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants	33 Participants	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	6 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) White	13 Participants	26 Participants	13 Participants
Sex: Female, Male Female	17 Participants	34 Participants	17 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 / 17	0 / 17
other Total, other adverse events	1 / 17	1 / 17
serious Total, serious adverse events	0 / 17	0 / 17

Outcome results

Primary

Time to Active Labor

Active phase of labor defined as greater than or equal to 6 cm cervical dilation

Time frame: from start of induction of labor (first misoprostol administration) to active phase of labor, up to 3 days.

Population: Subjects who reached active phase of labor.

Arm	Measure	Value (MEAN)	Dispersion
Oral Misoprostol	Time to Active Labor	19.8 hours	Standard Deviation 10.6
Vaginal Misoprostol	Time to Active Labor	21.4 hours	Standard Deviation 10.3

p-value: 0.09t-test, 1 sided

Secondary

Cesarean Section Rate

Number of cesarean sections/total deliveries (%)

Time frame: From enrollment until delivery, up to 3 days

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Oral Misoprostol	Cesarean Section Rate	2 Participants
Vaginal Misoprostol	Cesarean Section Rate	7 Participants

p-value: 0.12Fisher Exact

Secondary

Neonatal Morbidity

binary composite outcome defined as Apgar score \< 7, or cord blood gas pH of less than 7 or base deficit great than 12, or neonatal intensive care unit admission within 4 hours of delivery.

Time frame: 4 hours from delivery

Population: Excludes neonates with APGAR score\>7 not admitted to NICU but were missing cord blood gas results

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Oral Misoprostol	Neonatal Morbidity	2 Participants
Vaginal Misoprostol	Neonatal Morbidity	3 Participants

p-value: 1Fisher Exact

Secondary

Rate of Abandoning Misoprostol for Cervical Ripening and Switching to Mechanical Dilation for Cervical Ripening

Based on clinician's judgment on the progress of the induction, the rate that misoprostol administration was stopped and a cervical ripening balloon was used instead