Comparison Between 25 µg Vaginal Misoprostol vs Slow Release Pessary PGE2

Study Overview
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Brief Summary
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For about 10% of pregnancies, it is necessary to induce delivery for medical reasons. Prostaglandins alone can be used to perform cervical ripening in cases of immature cervix. In France, dinoprostone is the own approved medication. It is in the form of gel or sustained release device whose effectiveness and side effects are comparable. The vaginal misoprostol has no marketing authorization in France, but is sometimes used. Some data in the scientific literature have showed that its use with low-dose (25 mcg) vaginally did not lead to more complications, was at least as effective and seems to be cost-effective compared with dinoprostone. Misoprostol with this dose and route of administration is now recommended by the American College of Obstetricians and Gynecologist (ACOG), Grade A (ACOG Practice Bulletin August 2009). This is not the case in France (French HAS 2008 Guidelines on induction of labor). According to HAS, the investigators still lack data on large samples to confirm the benefits of misoprostol 25 mcg vaginally, in terms of efficiency, rate of cesarean section, and lower cost compared to dinoprostone. The primary objective is to demonstrate non-inferiority of vaginal misoprostol 25 mcg vs. dinoprostone in terms of cesarian section occurence with a non-inferiority margin of +5% difference.

Detailed Description
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To show if the experimental treatment (25μg of intravaginal misoprostol) used for induction of labor in singleton women ≥ 36 weeks gestation with an unfavorable cervix is not clinically and statistically inferior than the reference treatment , ie intravaginal dinoprostone sustained release (10mg), in terms of cesarian sectionto compare the cost-effectiveness and to assess the differential tolerance of the two strategies. Non-inferiority will be demonstrated if the upper limit of the 90%-bilateral confidence interval of the difference between cesarian section rates (misoprostol - dinosprostone) is below 5% in the intention-to-treat analysis and the per-protocol analysis. If non-inferiority is demonstrated, as a secondary analysis, superiority of misosprostol will be tested. Orther secondary objectives are to assess the cost-effectiveness, the tolerance, maternal satisfaction and other efficacy endpoints of the two strategies.

Official Title
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Comparison Between 25 µg Vaginal Misoprostol Versus Slow Release Pessary Prostaglandin-E2 (PGE2) : Could we Use Low Dose Vaginal Misoprostol as a First Line Treatment for Induction of Labor ?

Conditions
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Delivery Uterine

Intervention / Treatment
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* Drug: Misoprostol
* Drug: Dinoprostone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: singleton pregnancy Cephalic presentation Bishop ≤ 5 ≤ 3 uterine contractions / 10 mn ≥ 36 weeks gestation Personally signed and dated informed consent document Exclusion Criteria: History of cesarian-section uterine scar deceleration on Cardiotocogram (CTG) placenta praevia bleeding chorioamnionitis Fetal weight US ≥4500 g Contra-indication to vaginal delivery Hystory of myomectomy Herpes primoinfection or recurrence Allergy to prostaglandins

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Misoprostol<br>one 25 micrograms capsule all 4 hours by intravaginal route | Drug: Misoprostol<br>* administration of Misoprostol 25 micrograms capsule by intravaginal route every 4 hours, up to 4 capsules<br>* Other names: 25 micrograms Misoprostol capsule by intravaginal route;|
| Active Comparator: Dinoprostone<br>one unique intravaginal sustained released of 10 milligrams | Drug: Dinoprostone<br>* administration of one sustained released pessary of 10 milligrams by intravaginal route<br>* Other names: one intravaginal sustained released capsule of 10 milligrams;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cesarean for all indications | Occurrence of cesarean section for all indications | Up to delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-effectiveness of two strategies (direct medical cost differential efficiency strategies measured by the Cesarean rate |  | Up to discharge / end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction of labor, cervical ripening, misoprostol,, prostaglandin, cost-effectiveness