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

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 (MVI) 200 microgram (mcg) can decrease the time to vaginal delivery compared to the Dinoprostone Vaginal Insert (DVI) 10 milligram (mg) in pregnant women requiring cervical ripening and induction of labor.

Official Title
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Phase III, Double-blind, Randomized, Multicenter Study of Exogenous Prostaglandin Comparing the Efficacy & Safety of the MVI 200 mcg Versus the Dinoprostone Vaginal Insert (DVI) for Reducing Time to Vaginal Delivery in Pregnant Women at Term

Conditions
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Reducing Time to Vaginal Delivery, Cervical Ripening, Induction of Labor

Intervention / Treatment
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* Drug: MVI 200
* Drug: Dinoprostone Vaginal Insert (DVI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent; Pregnant women at ≥ 36 weeks 0 days inclusive gestation; Women aged 18 years or older; Candidate for pharmacological induction of labor; Single, live vertex fetus; Baseline modified Bishop score ≤ 4; Parity ≤ 3 (parity is defined as one or more births live or dead after 24 weeks gestation); Body Mass Index (BMI) ≤ 50 at the time of entry to the study. Exclusion Criteria: Women in active labor; Presence of uterine or cervical scar or uterine abnormality e.g., bicornate uterus. Biopsies, including cone biopsy of the cervix, are permitted; Administration of oxytocin or any cervical ripening or labor inducing agents (including mechanical methods) or a tocolytic drug within 7 days prior to enrollment. Magnesium sulfate is permitted if prescribed as treatment for pre-eclampsia or gestational hypertension; Severe pre-eclampsia marked by Hemolytic anemia, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, other end-organ affliction or Central Nervous System (CNS) findings other than mild headache; Fetal malpresentation; Diagnosed congenital anomalies, not including polydactyly; Any evidence of fetal compromise at baseline (e.g., non-reassuring fetal heart rate pattern or meconium staining); Amnioinfusion or other treatment of non-reassuring fetal status at any time prior to the induction attempt; Ruptured membranes ≥ 48 hours prior to the start of treatment; Suspected chorioamnionitis; Fever (oral or aural temperature > 37.5°C); Any condition in which vaginal delivery is contraindicated e.g., placenta previa or any unexplained genital bleeding at any time after 24 weeks during this pregnancy; Known or suspected allergy to misoprostol, dinoprostone, other prostaglandins or any of the excipients; Any condition urgently requiring delivery; Unable to comply with the protocol.

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 200<br>MVI 200 mcg vaginal insert | Drug: MVI 200<br>* 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.<br>* Other names: Misodel (R);|
| Active Comparator: Dinoprostone Vaginal Insert (DVI)<br>10 mg Dinoprostone vaginal insert | Drug: Dinoprostone Vaginal Insert (DVI)<br>* 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.<br>* Other names: Propess (R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Vaginal Delivery During the First Hospital Admission |  | Interval from study drug administration to vaginal delivery (average 24 hours) | 
| Incidence of Cesarean Delivery During the First Hospital Admission |  | Interval from study drug administration to cesarean delivery (average 24 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Any Delivery (Vaginal or Cesarean) During the First Hospital Admission |  | Interval from study drug administration to neonate delivery (average 24 hours) | 
| Time to Active Labor During the First Hospital Admission | 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. | Interval from study drug administration to active labor (average 12 hours) | 
| Incidence of Pre-delivery Oxytocin During the First Hospital Admission | Percentage of participants in receipt of Oxytocin for induction after study drug removal. | At least 30 minutes after study drug removal | 
| Incidence of Vaginal Delivery Within 12 Hours |  | Interval from study drug administration to vaginal delivery within 12 hours | 
| Incidence of Any Delivery Within 24 Hours |  | Interval from study drug administration to delivery of neonate within 24 hours | 
| Incidence of Any Delivery Within 12 Hours |  | Interval from study drug administration to delivery of neonate within 12 hours | 
| Incidence of Vaginal Delivery Within 24 Hours |  | Interval from study drug administration to vaginal delivery within 24 hours | 
| Incidence of Vaginal Delivery |  | Interval from study drug administration to vaginal delivery (average 24 hours) | 
| Rate of Adverse Events | 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. | From study drug administration to hospital discharge (approximately 48-72 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Misoprostol vaginal insert, Dinoprostone vaginal insert, Cervidil, Cervical ripening, Induction of labor, Rate of cesarean section