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

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the misoprostol vaginal insert (50 mcg and 100 mcg) can safely and effectively speed time to vaginal delivery compared to Cervidil (R) in women who need to have cervical ripneing and induction of labor.

Detailed Description
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Induction of labor is required in approximately 20% of pregnant women. Although contractions can be brought on by oxytocin (pitocin), some women need help in softening the cervix, or mouth of the womb (uterus), before oxytocin can be started. Prostaglandins have been shown to ripen, or soften, the cervix; at present, the only prostaglandin approved for marketing by FDA for this purpose is dinoprostone. Dinoprostone can be delivered in several ways; one method is to use a polymer vaginal insert that slowly releases the dinoprostone directly to the cervical tissues. This product is called Cervidil (R) and has been marketed for more than 10 years in the United States. Misoprostol is another form of prostaglandin that is approved for protecting the stomach and intestinal lining for patients taking NSAIDs. Misoprostol has also been used by many obstetricians for cervical ripening and inducing contractions, but, it is not approved by FDA for this purpose. The same company that makes the Cervidil polymer insert has made an insert that will slowly release misoprostol. This study will determine whether this investigational insert containing misoprostol will decrease time to vaginal delivery compared to Cervidil. Two different doses of misoprostol will be tested (50 micrograms and 100 micrograms); each vaginal insert will gradually release a small, controlled amount of misoprostol over up to 24 hours. Comparator: The Cervidil (R) vaginal insert containing dinoprostone will be the comparator in this study.

Official Title
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A Multi-center, Randomized, Double-blind Phase III Study of the Efficacy and Safety of the Misoprostol Vaginal Insert Compared to Cervidil for Women Requiring Cervical Ripening and Induction of Labor (The MVP Study).

Conditions
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Cervical Ripening, Labor, Induced

Intervention / Treatment
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* Drug: Misoprostol vaginal insert 100 mcg
* Drug: Misoprostol vaginal insert 50 mcg
* Drug: Dinoprostone vaginal insert (Cervidil)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women at least 36 weeks gestation requiring cervical ripening and induction of labor Exclusion Criteria: No uterine scar (no previous delivery by cesarean section) No multiple gestation No condition that disallows use of prostaglandins for induction of labor No more than 3 previous vaginal births beyond 24 weeks gestation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MVI 100<br>Misoprostol vaginal insert 100 mcg over 24h | Drug: Misoprostol vaginal insert 100 mcg<br>* Hydrogel polymer intravaginal insert with retrieval system. One insert is to remain in the posterior fornix of the vagina until removed for one of the following conditions: onset of active labor; maternal/fetal complication, e.g. non-reassuring fetal heart rate. Record if the insert falls out prior to meeting one of the first two criteria. In no case is the insert to remain in place longer than 24h.<br>* Other names: Misopess(TM);|
| Experimental: MVI 50<br>Misoprostol vaginal insert 50 mcg over 24h | Drug: Misoprostol vaginal insert 50 mcg<br>* Hydrogel polymer intravaginal insert with retrieval system. One insert is to remain in the posterior fornix of the vagina until removed for one of the following conditions: onset of active labor; maternal/fetal complication, e.g. non-reassuring fetal heart rate. Record if the insert falls out prior to meeting one of the first two criteria. In no case is the insert to remain in place longer than 24h.<br>* Other names: Misopess(TM);|
| Active Comparator: Cervidil 10 mg vaginal insert<br>Cervidil 10 mg over 24h | Drug: Dinoprostone vaginal insert (Cervidil)<br>* Hydrogel polymer intravaginal insert with retrieval system. One insert is to remain in the posterior fornix of the vagina until removed for one of the following conditions: onset of active labor; maternal/fetal complication, e.g. non-reassuring fetal heart rate. Record if the insert falls out prior to meeting one of the first two criteria. In no case is the insert to remain in place longer than 24h.<br>* Other names: 10 mg dinoprostone vaginal insert;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minutes From Drug Insertion to Vaginal Delivery | 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. | 2880 minutes | 
| Percentage of Participants With a Cesarean Section Delivery | 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. | 2880 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Maternal/Fetal, Maternal (Post-Partum), and Neonatal Adverse Events | 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. | 96 hours | 
| Percentage of Participants With Pre-Delivery Oxytocin Use | Incidence in each treatment group of need for oxytocin for pre-delivery induction or augmentation of labor. | 2880 minutes | 
| Percentage of Participants With Cervical Ripening Success Based On Modified Bishop Score (mBS) 12 Hours After Administration of Vaginal Insert | 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. | 12 hours | 
| Minutes to Onset of Active Labor | 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. | 2880 minutes | 
| Minutes to Rupture of Membranes (ROM) | Interval from study drug insertion to ROM. | 2880 minutes | 
| Duration of Stay in Minutes in Labor and Delivery Suite | Minutes in Labor and Delivery (L & D) suite starting from insertion of the study drug to discharge from L & D to post partum care. | 5760 minuts | 
| Days in Hospital for Mother and Neonate | Duration of stay in hospital for mother and neonate starting with insertion of the study drug and ending with discharge from the hospital. | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical ripening, Induction of labor, Dinoprostone vaginal insert, Cervidil, Misoprostol vaginal insert, Modified Bishop's Score, PGE2, PGE1, Uterine Hyperstimulation, Cesarean section