Safety and Efficacy Study of Misoprostol Vaginal Insert for Induction of Labour

Study Overview
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Brief Summary
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The primary objective of the study was assessment of the efficacy of four dose reservoirs (25 mcg, 50 mcg, 100 mcg, 200 mcg) of intravaginal controlled release misoprostol administered for up to 24 hours. Efficacy was measured in terms of time from insert placement to vaginal delivery.

Detailed Description
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Approximately 20% of pregnant women require medical intervention to induce labour for reasons including post-date pregnancy, pre-eclampsia, maternal diabetes, premature rupture of the membranes and intra-uterine fetal growth retardation. There are two fundamental changes that characterise pre-labour preparation for delivery: sensitisation of the myometrium to produce contractions, and ripening (softening and dilation) of the cervix. Prostaglandins (PG) are fundamental to both of these changes, and several forms have been used to successfully induce labour. Dinoprostone (PGE2) is an example of a cervical ripening agent that is available in gel and tablet form and has a proven record of successful cervical ripening in this population. Dinoprostone is also available in a controlled release vaginal delivery system, which is manufactured by Controlled Therapeutics (Scotland) a subsidiary of Cytokine PharmaSciences, Inc., King of Prussia, PA, USA. Another synthetic prostaglandin that has been shown to be an effective cervical ripener and labour inducer is misoprostol. Oral tablets are broken into fragments and used intravaginally to ripen the cervix and induce labour Due to the disadvantages of existing cervical ripeners (delivery of bolus doses, freezer or refrigerated storage, lack of efficacy in labour induction), and due to safety concerns with the off-label use of oral misoprostol tablet fragments, Controlled Therapeutics has developed a controlled release vaginal delivery system similar to its marketed dinoprostone product but containing misoprostol. This study examines four dose strengths of the misoprostol vaginal insert in women who need to have their labours induced.

Official Title
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Controlled-Release Misoprostol Vaginal Insert in Parous Women for Labor Induction: Randomized Trial

Conditions
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Labor Induction, Cervical Ripening

Intervention / Treatment
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* Drug: Misoprostol vaginal insert 25 mcg
* Drug: Misoprostol vaginal insert 50 mcg
* Drug: Misoprostol vaginal insert 100 mcg
* Drug: Misoprostol vaginal insert 200 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At term (37 to 42 weeks inclusive gestation). Aged 18 years or older. One previous full term delivery (at least 37 weeks gestation). Singleton pregnancy. Cephalic presentation (normal lie). Bishop score more than 6 as determined by MBS criteria. Uncomplicated pregnancy as judged by the physician. Written informed consent. Exclusion Criteria: four previous full term deliveries. Previous uterine surgery, including C-section and surgery to the cervix of the uterus (cone biopsy of the cervix is permitted). In spontaneous labour. Administration of oxytocin or a tocolytic drug or any other cervical ripening or labour inducing agent prior to enrolment (within seven days of enrolment). Suspected cephalo-pelvic disproportion. Evidence or suggestion of fetal distress. Subject has received NSAID (including aspirin) within four hours of study treatment (topical is permitted). Pyrexia (oral or aural temperature > 37.5C). Unexplained genital bleeding during this pregnancy after 24 weeks. Current pelvic inflammatory disease, unless adequate prior treatment has been instituted. Placenta praevia. Known or suspected allergy to misoprostol or other prostaglandins. Prior serious adverse event related to prostaglandin administered by any route for any indication. Subject unable to comply with the requirements of 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 25<br>Misoprostol vaginal insert 25 mcg | Drug: Misoprostol vaginal insert 25 mcg<br>* One hydrogel polymer vaginal insert for up to 24h<br>* Other names: Misoprostol vaginal insert;|
| Experimental: MVI 50<br>Misoprostol vaginal insert 50 mcg | Drug: Misoprostol vaginal insert 50 mcg<br>* One hydrogel polymer vaginal insert for up to 24h<br>* Other names: Misoprostol vaginal insert;|
| Experimental: MVI 100<br>Misoprostol vaginal insert 100 mcg | Drug: Misoprostol vaginal insert 100 mcg<br>* One hydrogel polymer vaginal insert for up to 24h<br>* Other names: Misoprostol vaginal insert;|
| Experimental: MVI 200<br>Misoprostol vaginal insert 200 mcg | Drug: Misoprostol vaginal insert 200 mcg<br>* One hydrogel polymer vaginal insert for up to 24h<br>* Other names: Misoprostol vaginal insert;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to vaginal delivery. |  | From insertion of study drug to neonate delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| uterine hyperstimulation |  | From insertion of study drug to neonate delivery | 
| safety in terms of maternal, fetal and neonatal adverse events |  | From insertion of study drug to neonate delivery | 
| Success on composite modified Bishop score (MBS)at 12 hours after drug insertion |  | From insertion of study drug to 12 hours | 
| frequency and amount of oxytocin use |  | From insertion of study drug to neonate delivery | 
| drug release characteristics in terms of residual concentrations |  | From insertion of study drug to removal of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Labor induction, cervical ripening, misoprostol, vaginal insert