Trial Outcomes & Findings for Buccal Versus Vaginal Misoprostol for Third Trimester Induction of Labor (NCT NCT01519765)

NCT ID: NCT01519765

Last Updated: 2016-09-27

Results Overview

Percentage of participants able to achieve vaginal delivery within 24 hours of labor induction.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 73 participants
• Primary outcome timeframe: Within 24 hours of labor induction
• Results posted on: 2016-09-27

Participant Flow

Participant milestones

Measure	Buccal Misoprostol Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. The same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Overall Study STARTED	37	36
Overall Study COMPLETED	34	34
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Measure	Buccal Misoprostol Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. The same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Overall Study Adverse Event	0	1
Overall Study Lack of Efficacy	2	0
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Buccal Versus Vaginal Misoprostol for Third Trimester Induction of Labor

Baseline characteristics by cohort

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. The same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.	Total n=68 Participants Total of all reporting groups
Age, Continuous	28.6 years STANDARD_DEVIATION 6.3 • n=93 Participants	30 years STANDARD_DEVIATION 6.51 • n=4 Participants	29.3 years STANDARD_DEVIATION 6.39 • n=27 Participants
Sex: Female, Male Female	34 Participants n=93 Participants	34 Participants n=4 Participants	68 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	34 participants n=93 Participants	34 participants n=4 Participants	68 participants n=27 Participants
Gestational age	40.2 weeks n=93 Participants	40.8 weeks n=4 Participants	40.5 weeks n=27 Participants
Bishop score	3 scores on a scale n=93 Participants	3 scores on a scale n=4 Participants	3 scores on a scale n=27 Participants
Parity Multiparous	9 participants n=93 Participants	9 participants n=4 Participants	18 participants n=27 Participants
Parity Nulliparous	25 participants n=93 Participants	25 participants n=4 Participants	50 participants n=27 Participants
Induction indication Post dates	15 participants n=93 Participants	16 participants n=4 Participants	31 participants n=27 Participants
Induction indication Hypertensive disorder	4 participants n=93 Participants	7 participants n=4 Participants	11 participants n=27 Participants
Induction indication Diabetes	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Induction indication Elective	7 participants n=93 Participants	3 participants n=4 Participants	10 participants n=27 Participants
Induction indication Oligohydramnios	1 participants n=93 Participants	3 participants n=4 Participants	4 participants n=27 Participants
Induction indication Cholestasis	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Induction indication Other	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Fetal anomaly	6 participants n=93 Participants	1 participants n=4 Participants	7 participants n=27 Participants

PRIMARY outcome

Timeframe: Within 24 hours of labor induction

Percentage of participants able to achieve vaginal delivery within 24 hours of labor induction.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Vaginal Delivery Within 24 Hours of Labor Induction	14.7 percentage of participants Interval 2.6 to 26.8	23.5 percentage of participants Interval 9.1 to 38.0

SECONDARY outcome

Timeframe: Start of induction until vaginal delivery

Population: Participants who achieved vaginal delivery were included in the analysis

Time from start of induction to vaginal delivery was computed in participants who achieved vaginal delivery.

Outcome measures

Measure	Buccal Misoprostol n=20 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=24 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Time to Vaginal Delivery	33.3 hours Interval 18.1 to 55.1	26.5 hours Interval 3.7 to 44.9

SECONDARY outcome

Timeframe: Until delivery

Time from induction to delivery. All participants were included.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Time to Delivery	34.1 hours Interval 18.0 to 36.7	27.5 hours Interval 3.7 to 68.8

SECONDARY outcome

Timeframe: Until active labor

Time from induction to active labor. Active labor defined as 4 cm and above. P-value computed by Kruskal-Wallis test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Time to Active Labor	22.1 hours Interval 0.0 to 47.0	19.4 hours Interval 2.3 to 40.5

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants who delivered vaginally

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Rates of Vaginal Delivery	58.8 percentage of participants Interval 42.3 to 75.4	70.6 percentage of participants Interval 55.3 to 85.9

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants who underwent a cesarean delivery was computed. P-value was computed using Fisher's exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Cesarean Delivery Rate	41.2 percentage of participants Interval 24.4 to 58.0	29.4 percentage of participants Interval 13.9 to 45.0

SECONDARY outcome

Timeframe: Until delivery

Number of misoprostol 25 mcg doses used during induction of labor.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Number of Misoprostol Doses	2 doses Interval 1.0 to 6.0	2 doses Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants who presented with arrest of dilation. Arrest of dilation was determined by the delivering physician.

P-value was computed using Fisher exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Arrest of Dilation	29.4 percentage of participants Interval 13.9 to 45.0	14.7 percentage of participants Interval 2.6 to 26.8

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants who were determined as a failed induction of labor. Failed induction was defined as no cervical change despite 24 hours of pitocin or 12 hours of pitocin after rupture of membranes.

P value was computed by Fisher exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Failed Induction of Labor	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Until delivery

Percentage of patients that used pitocin during labor. P-values were computed using Fisher exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Pitocin	97.1 percentage of participants Interval 91.3 to 102.8	82.4 percentage of participants Interval 69.3 to 95.4

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants that required foley bulb use.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Foley Bulb	38.2 percentage of participants Interval 21.7 to 54.8	41.2 percentage of participants Interval 24.4 to 58.0

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants that required AROM

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Artificial Rupture of Membranes (AROM)	64.7 percentage of participants Interval 48.4 to 81.0	67.6 percentage of participants Interval 51.7 to 83.6

SECONDARY outcome

Timeframe: Until 4 hours of last misoprostol dose

Feta heart tracing was reviewed for every participant until 4 hours from last misoprostol dose.

Percentage of participants who presented with abnormal fetal heart tracing was computed.

Abnormal fetal heart tracing was defined as category 2 and 3 fetal heart tracing according to standard criteria.

Abnormal fetal heart tracing included any of the following tachycardia, bradycardia without absent variability, minimal variability, absent variability with or without recurrent decelerations, marked variability, prolonged deceleration and recurrent late deceleration, sinusoidal pattern.

P values were computed by Fisher exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Abnormal Fetal Heart Tracing (FHT)	15.2 percentage of participants Interval 2.7 to 27.6	20.6 percentage of participants Interval 6.8 to 34.4

SECONDARY outcome

Timeframe: Until 4 hours after last misoprostol dose

Feta heart tracing was reviewed for every participant until 4 hours from last misoprostol dose.

Percentage of participants who presented with tachysystole and abnormal fetal heart tracing was computed.

Abnormal fetal heart tracing was defined as category 2 and above. Tachysystole was defined as more than 5 uterine contractions within 10 minutes. P values were computed by Fisher exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Tachysystole With Abnormal FHT	5.9 percentage of participants Interval 0.0 to 13.9	8.8 percentage of participants Interval 0.0 to 18.5

SECONDARY outcome

Timeframe: Until 4 hours after last misoprostol dose

Fetal heart tracing was reviewed until 4 hours after last misoprostol dose. Percentage of participant with tachysystole were computed. Tachysystole was defined as more than five uterine contractions in 10 minutes. P value was computed using Fisher exact test

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Tachysystole	26.5 percentage of participants Interval 11.4 to 41.5	32.4 percentage of participants Interval 16.4 to 48.3

SECONDARY outcome

Timeframe: Until discharge from hospital

Percentage of participants whose baby was admitted to NICU was computed from time to delivery to time of hospital discharge.

P-value was computed using Fisher Exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Neonatal Intensive Care Unit (NICU) Admission	20.6 percentage of participants Interval 6.8 to 34.4	11.8 percentage of participants Interval 0.8 to 22.8

SECONDARY outcome

Timeframe: Until delivery

Percentage of participants who developed meconium was computed. Presence of meconium was evaluated by the delivering physician. P-value was computed using Fisher exact test.

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Meconium	23.5 percentage of participants Interval 9.1 to 38.0	23.5 percentage of participants Interval 9.1 to 38.0

SECONDARY outcome

Timeframe: Until 48 hours after delivery

Percentage of participants affected with chorioamnionitis

Outcome measures

Measure	Buccal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Chorioamnionitis	17.6 percentage of participants Interval 4.6 to 30.7	14.7 percentage of participants Interval 2.6 to 26.8

SECONDARY outcome

Timeframe: 5 minutes after delivery

Median (APGAR) score at 5 minutes after delivery. APGAR: Appearance, Pulse, Grimace, Activity, Respiration Apgar scale is determine by evaluating a newborn on 5 categories on a scale from 0 to 2, then summing up the five values.

Score range is 0 to 10. Score above 7 are generally normal. Score below 3 may indicated poor status.

Outcome measures

Measure	Buccal Misoprostol n=32 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=34 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
APGARS	9 score Interval 6.0 to 9.0	9 score Interval 7.0 to 9.0

SECONDARY outcome

Timeframe: Until 72 hours after delivery

Population: Patient surveys were requested from all participants however incomplete patient survey collection was obtained.

All patients were given a patient satisfaction survey. Patients were asked to use a Likert scale to rate their experience on the following:

Likert sub-scale: 1 to 5

1=Not at all/ Never to 5= Very Much/ Always

1. Nausea and vomiting 1=better outcome 5=worse outcome

2. effectiveness of misoprostol 1=worse outcome 5=better outcome

3. concerns of misoprostol 1=better outcome 5=worse outcome

4. overall labor experience 1=worse outcome 5=better outcome Patients will be followed for the duration of their labor(usually up to 72hrs). The satisfaction survey will be conducted after delivery but will evaluate side effects that they recollect in labor.

Outcome measures

Measure	Buccal Misoprostol n=21 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=25 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Patient Satisfaction With Buccal Versus Vaginal Misoprostol Administration. Nausea/ Vomiting	1 units on a scale Interval 1.0 to 4.0	1 units on a scale Interval 1.0 to 3.0
Patient Satisfaction With Buccal Versus Vaginal Misoprostol Administration. Effectiveness	4 units on a scale Interval 1.0 to 5.0	4 units on a scale Interval 1.0 to 5.0
Patient Satisfaction With Buccal Versus Vaginal Misoprostol Administration. Patient Concern	2 units on a scale Interval 1.0 to 4.0	1 units on a scale Interval 1.0 to 5.0
Patient Satisfaction With Buccal Versus Vaginal Misoprostol Administration. Labor satisfaction	4 units on a scale Interval 1.0 to 5.0	4 units on a scale Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: Until 72 hours after delivery

Population: All participants were given the survey however incomplete collection was obtained.

All patients were given a patient satisfaction survey after delivery. They were asked to select their preference for misoprostol intervention type: buccal, vaginal, or either.

Outcome measures

Measure	Buccal Misoprostol n=21 Participants Participants received misoprostol 25 mcg via buccal route and placebo pill via vaginal route. This same regimen was then repeated every four hours according to protocol.	Vaginal Misoprostol n=25 Participants Participants received misoprostol 25 mcg via vaginal route and placebo pill via buccal route. This same regimen was repeated every four hours according to protocol.
Patient Preference Buccal	19 participants	18 participants
Patient Preference Vaginal	1 participants	3 participants
Patient Preference Either	1 participants	4 participants

Adverse Events

Buccal Misoprostol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vaginal Misoprostol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Linh Tran

Stanford University

Phone: 925-642-2241

Email: lltran20@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place