Efficacy & Safety Study Comparing Misoprostol Vaginal Insert (MVI) Versus Dinoprostone Vaginal Insert (DVI) for Reducing Time to Vaginal Delivery (EXPEDITE)

• ClinicalTrials.gov Identifier: NCT01127581
• Recruitment Status: Completed
• First Posted: May 21, 2010
• Results First Posted: March 7, 2014
• Last Update Posted: May 1, 2014
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Reducing Time to Vaginal Delivery; Cervical Ripening; Induction of Labor
• Interventions: Drug: MVI 200; Drug: Dinoprostone Vaginal Insert (DVI)
• Enrollment: 1358

Participant Flow

Recruitment Details	Pregnant women who required to be induced were recruited at 35 sites in the US.
Pre-assignment Details

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Period Title: Overall Study
Started	678	680
Completed	678	680
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		MVI 200	Dinoprostone Vaginal Insert (DVI)	Total
Arm/Group Description		MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	Total of all reporting groups
Overall Number of Baseline Participants		678	680	1358
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	678 participants	680 participants	1358 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	678 100.0%	680 100.0%	1358 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	678 participants	680 participants	1358 participants
		26.2 (5.99)	25.9 (5.95)	26.0 (5.96)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	678 participants	680 participants	1358 participants
	Female	678 100.0%	680 100.0%	1358 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	678 participants	680 participants	1358 participants
		678	680	1358

Outcome Measures

1. Primary Outcome

Title	Time to Vaginal Delivery During the First Hospital Admission
Description	[Not Specified]
Time Frame	Interval from study drug administration to vaginal delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

Subjects who underwent a cesarean delivery during the first hospitalization were censored using the longest time interval from study drug administration to cesarean delivery, independent of treatment assignment. Subjects who were discharged prior to delivery or withdrew consent prior to delivery were also censored.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Median (95% Confidence Interval); Unit of Measure: minutes
	1292.00; (1200.00 to 1402.00)	1968.50; (1812.00 to 2093.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	Subjects who underwent a cesarean delivery during the first hospitalization were censored using the longest time interval from study drug administration to cesarean delivery during the first hospitalization, independent of treatment group. Subjects who, in their first hospitalization, were discharged prior to delivery or withdrew consent prior to delivery were censored using the longest time interval from study drug administration to labor and delivery discharge, independent of treatment group.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-677
	Estimation Comments	Sample size 675 per group provides 90% power to see an improvement of ≥320 minutes (20% improvement from DVI) in time to vaginal delivery between MVI 200 & DVI assuming a median time of 1600 minutes for DVI & 34% dropout rate based on 5% 2-sided test

2. Primary Outcome

Title	Incidence of Cesarean Delivery During the First Hospital Admission
Description	[Not Specified]
Time Frame	Interval from study drug administration to cesarean delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

Analysis was based on a between-treatment-group difference in the safety population. Subjects discharged prior to delivery, withdrew early without having a cesarean delivery or were lost-to-follow up were classified as not having the event.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	25.96; (22.70 to 29.43)	27.06; (23.75 to 30.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	The analysis of the cesarean delivery rates during the first hospitalization was based on a between-treatment-group difference. If the upper limit of the asymptotic two-sided 95% confidence interval of the difference in event rates (MVI minus DVI) was less than the calculated non-inferiority margin (10% relative to the DVI rate, i.e., 0.1 times DVI rate), then MVI 200 would be considered non-inferior to DVI.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A sample size of 675 subjects per group will provide a sufficient number of subjects to assess non-inferiority of MVI 200 with respect to rate of cesarean delivery, based on an alpha level of 5% and 80% power for a two-sided approach using a 10% non-inferiority limit (relative to the DVI rate), assuming a 30% rate of cesarean delivery in the DVI group compared to a 26% rate in the MVI 200 group.
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Populations
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95%; -5.79 to 3.59
	Estimation Comments	MVI 200 - DVI

3. Secondary Outcome

Title	Time to Any Delivery (Vaginal or Cesarean) During the First Hospital Admission
Description	[Not Specified]
Time Frame	Interval from study drug administration to neonate delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

Subjects who did not deliver during the first hospitalization were censored at the time of labour and delivery discharge.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Median (95% Confidence Interval); Unit of Measure: minutes
	1096.50; (1031.00 to 1170.00)	1639.50; (1573.00 to 1731.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	Subjects who did not deliver during the first hospitalization were censored using the longest time interval from study drug administration to labor and delivery discharge without delivery, independent of treatment group.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-543
	Estimation Comments	MVI 200 - DVI

4. Secondary Outcome

Title	Time to Active Labor During the First Hospital Admission
Description	Active labor was defined as progressive cervical dilatation to 4 cm with any frequency of contractions OR rhythmic, firm, adequate quality uterine contractions causing progressive cervical change occurring at a frequency of 3 or more in 10 minutes and lasting 45 seconds or more.
Time Frame	Interval from study drug administration to active labor (average 12 hours)

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Median (95% Confidence Interval); Unit of Measure: minutes
	726.50; (719.00 to 773.00)	1116.50; (1083.00 to 1352.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	Subjects who never went into active labor during the first hospitalization were censored using the longest time interval from study drug administration to delivery during the first hospitalization, independent of treatment group. Subjects who, in their first hospitalization, were discharged prior to delivery or withdrew consent prior to delivery were censored using the longest time interval from study drug administration to labor and delivery discharge, independent of treatment group.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-390
	Estimation Comments	MVI 200 - DVI

5. Secondary Outcome

Title	Incidence of Pre-delivery Oxytocin During the First Hospital Admission
Description	Percentage of participants in receipt of Oxytocin for induction after study drug removal.
Time Frame	At least 30 minutes after study drug removal

Outcome Measure Data

Analysis Population Description

Analysis population includes subjects who delivered during the first hospitalization.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	674	671
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	48.1; (44.24 to 51.92)	74.1; (70.58 to 77.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	-26
	Estimation Comments	MVI 200 - DVI

6. Secondary Outcome

Title	Incidence of Vaginal Delivery Within 12 Hours
Description	[Not Specified]
Time Frame	Interval from study drug administration to vaginal delivery within 12 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	19.76; (16.83 to 22.96)	8.38; (6.41 to 10.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	9.67
	Estimation Comments	MVI 200 - DVI

7. Secondary Outcome

Title	Incidence of Any Delivery Within 24 Hours
Description	[Not Specified]
Time Frame	Interval from study drug administration to delivery of neonate within 24 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	67.70; (64.03 to 71.21)	40.74; (37.02 to 44.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	26.96
	Estimation Comments	MVI 200 - DVI

8. Secondary Outcome

Title	Incidence of Any Delivery Within 12 Hours
Description	[Not Specified]
Time Frame	Interval from study drug administration to delivery of neonate within 12 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	23.16; (20.03 to 26.52)	9.26; (7.19 to 11.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	13.90
	Estimation Comments	MVI 200 - DVI

9. Secondary Outcome

Title	Incidence of Vaginal Delivery Within 24 Hours
Description	[Not Specified]
Time Frame	Interval from study drug administration to vaginal delivery within 24 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	54.57; (50.74 to 58.37)	33.97; (30.41 to 37.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	29.80
	Estimation Comments	MVI 200 - DVI

10. Secondary Outcome

Title	Incidence of Vaginal Delivery
Description	[Not Specified]
Time Frame	Interval from study drug administration to vaginal delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

The Intention-to-Treat (ITT) population was used for all secondary efficacy analyses.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	73.30; (69.80 to 76.60)	71.62; (68.07 to 74.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	1.68
	Estimation Comments	MVI 200 - DVI

11. Secondary Outcome

Title	Rate of Adverse Events
Description	All adverse events were rated by the Investigator as mild, moderate or severe and classified as having no relationship, possible relationship or a probable relationship to the study drug.
Time Frame	From study drug administration to hospital discharge (approximately 48-72 hours)

Outcome Measure Data

Analysis Population Description

The percentage of subjects with adverse events are presented for the Intrapartum (before delivery), postpartum (maternal) and neonatal periods.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description:	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
Overall Number of Participants Analyzed	678	680
Measure Type: Number; Unit of Measure: percentage of participants
Subjects with an Intrapartum Adverse Events	55.5	54.6
Subjects with Maternal Postpartum Adverse Events	21.4	21.2
Subjects with Neonatal Adverse Events	53.4	58.1

Adverse Events

Time Frame	All adverse events were followed until resolution or at least 30 days after discontinuation of the study drug, whichever occurred first.
Adverse Event Reporting Description	All adverse events occurring to the maternal-fetal unit (pre-delivery/ intrapartum), the mother (postpartum) or the neonate were recorded. Adverse events that resulted in a cesarean delivery were reported as serious adverse events as they were medically significant events that routinely prolonged the duration of hospitalization.
Arm/Group Title	MVI 200		Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert MVI 200: Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.		10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.
All-Cause Mortality
	MVI 200		Dinoprostone Vaginal Insert (DVI)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	MVI 200		Dinoprostone Vaginal Insert (DVI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	130/678 (19.17%)		107/680 (15.74%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation # † 1 [1]	1/678 (0.15%)	1	0/680 (0.00%)	0
Polycythaemia * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Cardiac disorders
Pericarditis # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Supraventricular tachycardia * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Supraventricular tachycardia + † 1 [3]	0/678 (0.00%)	0	1/680 (0.15%)	1
Congenital, familial and genetic disorders
Adrenogenital syndrome * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Anal atresia * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Ankyloglossia congenital * † 1 [2]	3/678 (0.44%)	3	2/680 (0.29%)	2
Anomalous pulmonary venous connection * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Atrial septal defect * † 1 [2]	8/678 (1.18%)	8	6/680 (0.88%)	6
Cataract congenital * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Congenital choroid plexus cyst * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Congenital hydronephrosis * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Congenital nose malformation * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Congenital pyelocaliectasis * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Cryptorchism * † 1 [2]	6/678 (0.88%)	6	2/680 (0.29%)	2
Hydrocele * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Hypospadias * † 1 [2]	4/678 (0.59%)	4	4/680 (0.59%)	4
Patent ductus arteriosus * † 1 [2]	4/678 (0.59%)	4	4/680 (0.59%)	4
Penile torsion * † 1 [2]	3/678 (0.44%)	3	1/680 (0.15%)	1
Phimosis * † 1 [2]	0/678 (0.00%)	0	3/680 (0.44%)	3
Pilonidal cyst congenital * † 1 [2]	3/678 (0.44%)	3	7/680 (1.03%)	7
Polydactyly * † 1 [2]	3/678 (0.44%)	3	3/680 (0.44%)	3
Pulmonary artery stenosis congenital * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Supernumerary nipple * † 1 [2]	0/678 (0.00%)	0	2/680 (0.29%)	2
Syndactyly * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Talipes * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
VACTERL syndrome * † 1 [2]	2/678 (0.29%)	2	0/680 (0.00%)	0
Ventricular septal defect * † 1 [2]	4/678 (0.59%)	4	1/680 (0.15%)	1
Eye disorders
Vitreous haemorrhage * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Gastrointestinal disorders
Anal fistula * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Intestinal obstruction * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Salivary gland enlargement * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
General disorders
Fever neonatal * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Infections and infestations
Endometritis # † 1 [1]	2/678 (0.29%)	2	1/680 (0.15%)	1
Pneumonia * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Pneumonia # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Postpartum sepsis # † 1 [1]	1/678 (0.15%)	1	0/680 (0.00%)	0
Sepsis neonatal * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Septic shock * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Injury, poisoning and procedural complications
Skull fracture * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Investigations
Urine output decreased * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Metabolism and nutrition disorders
Feeding disorder neonatal * † 1 [2]	1/678 (0.15%)	1	2/680 (0.29%)	2
Musculoskeletal and connective tissue disorders
Joint crepitation * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Muscular weakness # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Nervous system disorders
Dysaesthesia # † 1 [1]	1/678 (0.15%)	1	0/680 (0.00%)	0
Encephalopathy neonatal * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Hypoxic-ischaemic encephalopathy * † 1 [2]	4/678 (0.59%)	4	0/680 (0.00%)	0
Paraesthesia # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Pregnancy, puerperium and perinatal conditions
Abnormal labour affecting foetus + † 1 [3]	13/678 (1.92%)	13	0/680 (0.00%)	0
Drug withdrawal syndrome neonatal * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Erb's palsy * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Foetal acidosis * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Foetal heart rate disorder + † 1 [3]	65/678 (9.59%)	65	46/680 (6.76%)	46
Hypoglycaemia neonatal * † 1 [2]	3/678 (0.44%)	3	2/680 (0.29%)	2
Neonatal disorder * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Postpartum haemorrhage # † 1 [1]	2/678 (0.29%)	2	3/680 (0.44%)	3
Premature separation of placenta + † 1 [3]	1/678 (0.15%)	1	0/680 (0.00%)	0
Puerperal pyrexia # † 1 [1]	1/678 (0.15%)	1	0/680 (0.00%)	0
Retained placenta or membranes # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Uterine contractions abnormal + † 1 [3]	1/678 (0.15%)	1	0/680 (0.00%)	0
Uterine rupture + † 1 [3]	1/678 (0.15%)	1	0/680 (0.00%)	0
Weight decrease neonatal * † 1 [2]	1/678 (0.15%)	1	1/680 (0.15%)	1
Psychiatric disorders
Anxiety # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Renal and urinary disorders
Hydronephrosis * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Reproductive system and breast disorders
Chordee * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Testicular torsion * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Vulval haematoma # † 1 [1]	0/678 (0.00%)	0	1/680 (0.15%)	1
Respiratory, thoracic and mediastinal disorders
Neonatal aspiration * † 1 [2]	1/678 (0.15%)	1	2/680 (0.29%)	2
Neonatal respiratory depression * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Neonatal respiratory distress syndrome * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Pneumothorax * † 1 [2]	0/678 (0.00%)	0	1/680 (0.15%)	1
Transient tachypnoea of the newborn * † 1 [2]	1/678 (0.15%)	1	0/680 (0.00%)	0
Vascular disorders
Deep vein thrombosis # † 1 [1]	1/678 (0.15%)	1	0/680 (0.00%)	0
Hypertension # † 1 [1]	1/678 (0.15%)	1	1/680 (0.15%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (13.1); [1] # Postpartum Event; [2] * Neonatal Event; [3] + Intrapartum Event
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MVI 200		Dinoprostone Vaginal Insert (DVI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	520/678 (76.70%)		533/680 (78.38%)
Pregnancy, puerperium and perinatal conditions
Abnormal labour affecting foetus + † 1 [1]	59/678 (8.70%)	62	19/680 (2.79%)	19
Arrested labour + † 1 [1]	96/678 (14.16%)	96	128/680 (18.82%)	129
Caput succedaneum * † 1 [2]	58/678 (8.55%)	58	60/680 (8.82%)	60
Chorioamnionitis + † 1 [1]	38/678 (5.60%)	38	59/680 (8.68%)	59
Foetal heart rate disorder + † 1 [1]	124/678 (18.29%)	138	138/680 (20.29%)	160
Hyperbilirubinaemia neonatal * † 1 [2]	62/678 (9.14%)	62	78/680 (11.47%)	78
Meconium in amniotic fluid + † 1 [1]	120/678 (17.70%)	120	92/680 (13.53%)	92
Postpartum haemorrhage # † 1 [3]	40/678 (5.90%)	41	37/680 (5.44%)	37
Umbilical cord around neck * † 1 [2]	184/678 (27.14%)	184	194/680 (28.53%)	194
Respiratory, thoracic and mediastinal disorders
Neonatal respiratory depression * † 1 [2]	34/678 (5.01%)	34	30/680 (4.41%)	30
Surgical and medical procedures
Infection prophylaxis * † 1 [2]	46/678 (6.78%)	46	63/680 (9.26%)	63
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (13.1); [1] + Intrapartum Event; [2] * Neonatal Event; [3] # Postpartum Event

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Any abstract,presentation or manuscript proposed for publication must be submitted to the Sponsor for review at least 30 days prior to submission for any meeting or journal.If deemed necessary by the Sponsor for protection of proprietary information prior to patent filing,the Investigator agrees to a further delay of 60 days before any presentation or publication is submitted.Publications must be in a form that does not reveal technical information that is considered confidential or proprietary.

Results Point of Contact

• Name/Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals
• EMail: DK0-Disclosure@ferring.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miller H, Goetzl L, Wing DA, Powers B, Rugarn O. Optimising daytime deliveries when inducing labour using prostaglandin vaginal inserts. J Matern Fetal Neonatal Med. 2016;29(4):517-22. doi: 10.3109/14767058.2015.1011117. Epub 2015 Mar 16.

Wing DA, Brown R, Plante LA, Miller H, Rugarn O, Powers BL. Misoprostol vaginal insert and time to vaginal delivery: a randomized controlled trial. Obstet Gynecol. 2013 Aug;122(2 Pt 1):201-209. doi: 10.1097/AOG.0b013e31829a2dd6.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01127581
• Other Study ID Numbers: Miso-Obs-303
• First Submitted: May 19, 2010
• First Posted: May 21, 2010
• Results First Submitted: January 24, 2014
• Results First Posted: March 7, 2014
• Last Update Posted: May 1, 2014