Safety/Efficacy Study Comparing the Misoprostol Vaginal Insert to Cervidil for Cervical Ripening and Induction of Labor

• ClinicalTrials.gov Identifier: NCT00308711
• Recruitment Status: Completed
• First Posted: March 30, 2006
• Results First Posted: February 19, 2010
• Last Update Posted: June 25, 2012
• 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: Cervical Ripening; Labor, Induced
• Interventions: Drug: Misoprostol vaginal insert 100 mcg; Drug: Misoprostol vaginal insert 50 mcg; Drug: Dinoprostone vaginal insert (Cervidil)
• Enrollment: 1308

Participant Flow

Recruitment Details	First subject entered 26 April 2006; last subject completed 07 August 2007; 49 hospitals entered subjects requiring cervical ripening prior to induction of labor.
Pre-assignment Details

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Period Title: Overall Study
Started	428	444	436
Completed	426	440	431
Not Completed	2	4	5
Reason Not Completed
Withdrawal by Subject	1	0	1
Protocol Violation	0	1	1
Lost to Follow-up	0	1	0
Baby not born within 7 days of treatment	1	2	2
Subject incarcerated, data not allowed	0	0	1

Baseline Characteristics

Arm/Group Title		Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert	Total
Arm/Group Description		Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h	Total of all reporting groups
Overall Number of Baseline Participants		428	444	436	1308
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	428 participants	444 participants	436 participants	1308 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	428 100.0%	444 100.0%	436 100.0%	1308 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	428 participants	444 participants	436 participants	1308 participants
		26.2 (5.9)	26.9 (6.2)	26.0 (5.7)	26.4 (5.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	428 participants	444 participants	436 participants	1308 participants
	Female	428 100.0%	444 100.0%	436 100.0%	1308 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	428 participants	444 participants	436 participants	1308 participants
United States		413	427	419	1259
Canada		15	17	17	49
Parity [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	428 participants	444 participants	436 participants	1308 participants
Nulliparous		267	275	270	812
Parous		161	169	166	496
		[1] Measure Description: Nulliparaous = no previous vaginal delivery prior to 24 wks gestation Parous = at least one previous vaginal delivery after 24 weeks
modified Bishop score (mBS) [1]; Mean (Standard Deviation); Unit of measure: Units on a scale of 0 (low) to 12 (most)
	Number Analyzed	428 participants	444 participants	436 participants	1308 participants
		2.69 (1.1)	2.74 (1.1)	2.73 (1.1)	2.72 (1.1)
		[1] Measure Description: The mBS measures cervical softness. There are five elements assessed during a vaginal examination. Maximum mBS is 12: 0 to 3 for Dilation, 0 to 3 for Station, 0 to 2 for Consistency, 0 to 1 for Position, and 0 to 3 for Length of Cervix. A score of zero is a long, closed, thick firm cervix; a score of 12 indicates thin, completely soft, 100% effaced cervix.

Outcome Measures

1. Primary Outcome

Title	Minutes From Drug Insertion to Vaginal Delivery
Description	Interval between time/date of insertion of study drug and time/date of neonate birth. This is a time-to-event analysis, there is no set time for the assessment. The endpoint occurs when the baby is born. 48 hours can be used as an approximate interval by which time most of the babies have been delivered.
Time Frame	2880 minutes

Outcome Measure Data

Analysis Population Description

This analysis is for time to vaginal delivery (interval from insertion of study drug into the vagina to the delivery of the neonate); patients delivered by cesarean section were censored from this time-to-event analysis using the longest interval for all participants from insertion of study drug to cesarean section delivery of neonate.

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Median (95% Confidence Interval); Unit of Measure: minutes
	1595.5; (1469 to 1739)	2127; (1977 to 2253)	1649.5; (1509 to 1824)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Misoprostol Vaginal Insert (MVI) 100, Cervidil 10 mg Vaginal Insert
	Comments	Null hypothesis was that there would be no difference in time to vaginal delivery for MVI 100 compared to time to vaginal delivery for Cervidil.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.974
	Comments	The a priori threshold for statistical significance was 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Kaplan-Meier
	Estimated Value	1595.5
	Estimation Comments	This was a Kaplan-Meier analysis of median time to vaginal delivery. Cervidil was compared separately to MVI 100 and MVI 50.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Misoprostol Vaginal Insert (MVI) 50, Cervidil 10 mg Vaginal Insert
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.011
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1977
	Confidence Interval	95%; 1977 to 2253
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants With a Cesarean Section Delivery
Description	Percentage of participants with cesarean delivery after study drug was administered. There is no set assessment time or date as the woman's labor may last hours or days.
Time Frame	2880 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Measure Type: Number; Unit of Measure: Percentage of participants
	28	28	26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Misoprostol Vaginal Insert (MVI) 100, Cervidil 10 mg Vaginal Insert
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority (NI) margin was within 15% relative to the rate of cesarean section for the comparator (Cervidil 10 mg dinoprostone vaginal insert).
Statistical Test of Hypothesis	P-Value	0.64
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	27.8
	Confidence Interval	95%; 23.61 to 32.31
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Misoprostol Vaginal Insert (MVI) 50, Cervidil 10 mg Vaginal Insert
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin was rate of cearean section within 15% of Cervidil rate.
Statistical Test of Hypothesis	P-Value	0.59
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	28.0
	Confidence Interval	95%; 23.86 to 32.42
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants With Maternal/Fetal, Maternal (Post-Partum), and Neonatal Adverse Events
Description	This outcome reports the percentage of adverse events in each treatment arm spontaneously reported or observed during the study. The intrapartum period (mother is still pregnant) is called the "Maternal/Fetal" period; once the baby has been born, adverse events are assessed separately for the mother (Post Partum) and the baby (Neonatal). The number of adverse events was assessed separately for each of the three periods.
Time Frame	96 hours

Outcome Measure Data

Analysis Population Description

Analysis was based on intention to treat, i.e., all subjects who had the insert placed in the vagina.

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Measure Type: Number; Unit of Measure: Percentage of participants
Maternal/Fetal	65	64	65
Maternal (Post-Partum)	29	26	27
Neonatal	29	24	27

4. Secondary Outcome

Title	Percentage of Participants With Pre-Delivery Oxytocin Use
Description	Incidence in each treatment group of need for oxytocin for pre-delivery induction or augmentation of labor.
Time Frame	2880 minutes

Outcome Measure Data

Analysis Population Description

This analysis included all participants exposed to study drug and for whom there was data available regarding whether oxytocin was used pre-delivery.

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Measure Type: Number; Unit of Measure: Percentage of participants
	68.5	80.8	69.0

5. Secondary Outcome

Title	Percentage of Participants With Cervical Ripening Success Based On Modified Bishop Score (mBS) 12 Hours After Administration of Vaginal Insert
Description	Measured the percentage of participants who achieved success on the mBS. This composite score is based on the mBS and vaginal delivery and it is measured 12 hours after insertion of the study drug. The mBS has a score of 0 when the cervix is not ripe and a score of 12 when completely ripened. The 12 hour score is compared to baseline. Using the mBS, assess at 12 hours whether each subject has met any of the following three criteria: 1) has improved (increased) the mBS by at least 3 points from baseline; 2) has reached a score of at least 6 on the mBS; or 3) has acheived a vaginal delivery.
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Measure Type: Number; Unit of Measure: Percentage of Participants
	59	50	60

6. Secondary Outcome

Title	Minutes to Onset of Active Labor
Description	Interval from insertion of study drug to onset of active labor, defined as at least three contractions in a ten-minute period of at least moderate intensity and resulting in cervical change such as dilatation or effacement; OR at least 4 cm cervical dilatation achieved after progressive change in dilatation.
Time Frame	2880 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Mean (Standard Deviation); Unit of Measure: minutes
	1032.5 (627.2)	1343.7 (692.0)	1005.2 (667.1)

7. Secondary Outcome

Title	Minutes to Rupture of Membranes (ROM)
Description	Interval from study drug insertion to ROM.
Time Frame	2880 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Median (95% Confidence Interval); Unit of Measure: minutes
	1285.0; (906.0 to 2208.0)	1364.0; (1048 to 2491)	1123; (915 to 1580)

8. Secondary Outcome

Title	Duration of Stay in Minutes in Labor and Delivery Suite
Description	Minutes in Labor and Delivery (L & D) suite starting from insertion of the study drug to discharge from L & D to post partum care.
Time Frame	5760 minuts

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Mean (Standard Deviation); Unit of Measure: minutes
	1683.6 (811)	2010 (850)	1729 (862)

9. Secondary Outcome

Title	Days in Hospital for Mother and Neonate
Description	Duration of stay in hospital for mother and neonate starting with insertion of the study drug and ending with discharge from the hospital.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100	Misoprostol Vaginal Insert (MVI) 50	Cervidil 10 mg Vaginal Insert
Arm/Group Description:	Misoprostol vaginal insert 100 mcg over a period of up to 24 h	Misoprostol vaginal insert 50 mcg over a period of up to 24 h	Cervidil 10 mg vaginal insert over a period of up to 24h
Overall Number of Participants Analyzed	426	440	431
Mean (Standard Deviation); Unit of Measure: days
Mother	4.5 (1.24)	4.7 (1.1)	4.5 (1.3)
Neonate	3.6 (1.8)	3.5 (1.2)	3.6 (1.6)

Adverse Events

Time Frame	96 hours
Adverse Event Reporting Description	Adverse event data were collected during the hospital period only. One subject in the MVI 50 group was incarcerated; her information was not permitted to be used for data analysis, therefore all results are based on 443 subjects for this treatment groups.
Arm/Group Title	Misoprostol Vaginal Insert (MVI) 100		Misoprostol Vaginal Insert (MVI) 50		Cervidil 10 mg Vaginal Insert
Arm/Group Description	Misoprostol vaginal insert 100 mcg over a period of up to 24 h		Misoprostol vaginal insert 50 mcg over a period of up to 24 h		Cervidil 10 mg vaginal insert over a period of up to 24h
All-Cause Mortality
	Misoprostol Vaginal Insert (MVI) 100		Misoprostol Vaginal Insert (MVI) 50		Cervidil 10 mg Vaginal Insert
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Misoprostol Vaginal Insert (MVI) 100		Misoprostol Vaginal Insert (MVI) 50		Cervidil 10 mg Vaginal Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	106/428 (24.77%)		134/443 (30.25%)		117/436 (26.83%)
Blood and lymphatic system disorders
Thrombocytopenia * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
Anaemia * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
polycythaemia * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
Cardiac disorders
Wolff-Parkinson-White Syndrome * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
Cardiac Failure Congestive * 1	3/428 (0.70%)	3	2/443 (0.45%)	2	1/436 (0.23%)	1
congestive cardiomyopathy * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
Tachycardia * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
Chest pain * 1	2/428 (0.47%)	2	0/443 (0.00%)	0	1/436 (0.23%)	1
bradycardia neonatal * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	1/436 (0.23%)	1
tachcardia foetal * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
Congenital, familial and genetic disorders
congenital anomaly * 1	10/428 (2.34%)	10	7/443 (1.58%)	7	7/436 (1.61%)	7
Gastrointestinal disorders
Ileus * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
General disorders
Pyrexia * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	1/436 (0.23%)	1
Neonatal hypothermia * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
Hepatobiliary disorders
Liver abscess * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
hyperbilirubinemia neonatal * 1	6/428 (1.40%)	6	5/443 (1.13%)	5	8/436 (1.83%)	8
Infections and infestations
Herpes Simplex * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
Endometritis * 1	2/428 (0.47%)	2	2/443 (0.45%)	2	3/436 (0.69%)	3
cellulitis * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
pyelonephritis * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	2/436 (0.46%)	2
wound infection * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	1/436 (0.23%)	1
Group B sepsis neonatal * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
sepsis * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	1/436 (0.23%)	1
Investigations
urine output decreased * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
Apgar score low * 1	4/428 (0.93%)	4	2/443 (0.45%)	2	2/436 (0.46%)	2
Nervous system disorders
peroneal nerve palsy * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
Pregnancy, puerperium and perinatal conditions
Arrested Labor * 1 [1]	25/428 (5.84%)	25	36/443 (8.13%)	36	33/436 (7.57%)	33
Cephalopelvic Disproportion * 1	14/428 (3.27%)	14	35/443 (7.90%)	35	29/436 (6.65%)	29
Abnormal Labor Affecting Fetus * 1	2/428 (0.47%)	2	0/443 (0.00%)	0	0/436 (0.00%)	0
Chorioamnionitis * 1	0/428 (0.00%)	0	4/443 (0.90%)	4	0/436 (0.00%)	0
Foetal heart rate disorder * 1	46/428 (10.75%)	46	47/443 (10.61%)	47	35/436 (8.03%)	35
Foetal malpresentation * 1	4/428 (0.93%)	4	3/443 (0.68%)	3	6/436 (1.38%)	6
Pregnancy-induced hypertension * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
Premature separation of placenta * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
umbilical cord prolapse * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	5/436 (1.15%)	5
uterine contractions abnormal * 1	1/428 (0.23%)	1	1/443 (0.23%)	1	0/436 (0.00%)	0
uterine hypertonus * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
postpartum hemorrhage * 1	1/428 (0.23%)	1	4/443 (0.90%)	4	4/436 (0.92%)	4
preeclampsia * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
ABO hemolytic disease of the newborn * 1	9/428 (2.10%)	9	8/443 (1.81%)	9	3/436 (0.69%)	3
cephalohaematoma * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
jaundice * 1	2/428 (0.47%)	2	2/443 (0.45%)	2	1/436 (0.23%)	1
Renal and urinary disorders
nephrolithiasis * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	2/436 (0.46%)	2
urinary retention * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
Reproductive system and breast disorders
uterine atony * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	1/436 (0.23%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema * 1	0/428 (0.00%)	0	0/443 (0.00%)	0	1/436 (0.23%)	1
dyspnoea * 1	2/428 (0.47%)	2	2/443 (0.45%)	2	0/436 (0.00%)	0
pleuritic pain * 1	0/428 (0.00%)	0	1/443 (0.23%)	1	0/436 (0.00%)	0
pulmonary embolism * 1	1/428 (0.23%)	1	0/443 (0.00%)	0	0/436 (0.00%)	0
neonatal aspiration * 1	2/428 (0.47%)	2	1/443 (0.23%)	1	4/436 (0.92%)	4
neonatal respiratory depression * 1	5/428 (1.17%)	5	1/443 (0.23%)	1	5/436 (1.15%)	5
neonatal respiratory distress syndrome * 1	2/428 (0.47%)	2	3/443 (0.68%)	3	4/436 (0.92%)	4
transient tachypnea of the newborn * 1	1/428 (0.23%)	1	1/443 (0.23%)	1	4/436 (0.92%)	4
Surgical and medical procedures
infection prophylaxis * 1	2/428 (0.47%)	2	3/443 (0.68%)	3	2/436 (0.46%)	2
Vascular disorders
hypertension * 1	2/428 (0.47%)	2	0/443 (0.00%)	0	0/436 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (6.1); [1] Also included terms such as Failure to progress
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2.0%
	Misoprostol Vaginal Insert (MVI) 100		Misoprostol Vaginal Insert (MVI) 50		Cervidil 10 mg Vaginal Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	130/428 (30.37%)		129/443 (29.12%)		132/436 (30.28%)
Blood and lymphatic system disorders
Anemia * 1	21/428 (4.91%)	21	25/443 (5.64%)	25	20/436 (4.59%)	20
Hepatobiliary disorders
neonatal hyperbilirubinemia * 1	9/428 (2.10%)	9	6/443 (1.35%)	6	15/436 (3.44%)	15
Investigations
Apgar score low * 1	10/428 (2.34%)	10	10/443 (2.26%)	10	10/436 (2.29%)	10
Pregnancy, puerperium and perinatal conditions
Abnormal labour affecting foetus * 1	24/428 (5.61%)	24	12/443 (2.71%)	12	28/436 (6.42%)	28
Chorioamnionitis * 1	17/428 (3.97%)	17	30/443 (6.77%)	30	22/436 (5.05%)	22
Foetal heart rate disorder * 1	130/428 (30.37%)	130	129/443 (29.12%)	129	132/436 (30.28%)	132
Meconium in amniotic fluid * 1	38/428 (8.88%)	38	45/443 (10.16%)	45	44/436 (10.09%)	44
uterine contractions abnormal * 1	83/428 (19.39%)	86	61/443 (13.77%)	63	81/436 (18.58%)	89
uterine hypertonus * 1	17/428 (3.97%)	17	16/443 (3.61%)	16	25/436 (5.73%)	25
Perineal laceration * 1	21/428 (4.91%)	21	28/443 (6.32%)	28	21/436 (4.82%)	21
post partum hemorrhage * 1	17/428 (3.97%)	17	16/443 (3.61%)	16	21/436 (4.82%)	21
Vascular disorders
Hypotension * 1	18/428 (4.21%)	18	21/443 (4.74%)	21	23/436 (5.28%)	23
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (6.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

• Name/Title: Barbara L. Powers
• Organization: Cytokine PharmaSciences, Inc.
• Phone: 610-687-1776 ext 214
• EMail: bpowers@cytokinepharmasciences.com

Publications of Results:

Wing DA; Misoprostol Vaginal Insert Consortium. Misoprostol vaginal insert compared with dinoprostone vaginal insert: a randomized controlled trial. Obstet Gynecol. 2008 Oct;112(4):801-12. doi: 10.1097/AOG.0b013e318187042e.

Pevzner L, Rayburn WF, Rumney P, Wing DA. Factors predicting successful labor induction with dinoprostone and misoprostol vaginal inserts. Obstet Gynecol. 2009 Aug;114(2 Pt 1):261-267. doi: 10.1097/AOG.0b013e3181ad9377.

Other Publications:

Castaneda CS, Izquierdo Puente JC, Leon Ochoa RA, Plasse TF, Powers BL, Rayburn WF. Misoprostol dose selection in a controlled-release vaginal insert for induction of labor in nulliparous women. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1071-5. doi: 10.1016/j.ajog.2005.06.072.

Rayburn WF, Powers BL, Plasse TF, Carr D, Di Spirito M. Pharmacokinetics of a controlled-release misoprostol vaginal insert at term. J Soc Gynecol Investig. 2006 Feb;13(2):112-7. doi: 10.1016/j.jsgi.2005.10.004.

Ewert K, Powers B, Robertson S, Alfirevic Z. Controlled-release misoprostol vaginal insert in parous women for labor induction: a randomized controlled trial. Obstet Gynecol. 2006 Nov;108(5):1130-7. doi: 10.1097/01.AOG.0000239100.16166.5a.

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

Hawkins JS, Stephenson M, Powers B, Wing DA. Diabetes mellitus: an independent predictor of duration of prostaglandin labor induction. J Perinatol. 2017 May;37(5):488-491. doi: 10.1038/jp.2016.270. Epub 2017 Jan 26.

Brennan MC, Pevzner L, Wing DA, Powers BL, Rayburn WF. Retention of dinoprostone vaginal insert beyond 12 hours for induction of labor. Am J Perinatol. 2011 Jun;28(6):479-84. doi: 10.1055/s-0030-1271208. Epub 2011 Jan 11.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00308711
• Other Study ID Numbers: Miso-Obs-004
• First Submitted: March 27, 2006
• First Posted: March 30, 2006
• Results First Submitted: July 29, 2009
• Results First Posted: February 19, 2010
• Last Update Posted: June 25, 2012