Clinical trial NCT01765881: Comparison Between 25 µg Vaginal Misoprostol vs Slow Release Pessary PGE2
Official title: 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 ?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Delivery Uterine
Keywords: Induction of labor
cervical ripening
misoprostol,
prostaglandin
cost-effectiveness
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2013-01-10
Enrollment: 1700
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cesarean for all indications
timeFrame: Up to delivery
Secondary outcomes:
measure: Cost-effectiveness of two strategies (direct medical cost differential efficiency strategies measured by the Cesarean rate
timeFrame: Up to discharge / end of study
Other outcomes:
measure: Adverse events
timeFrame: Up to discharge/end of study
measure: Other specific safety assessments
timeFrame: Up to discharge/end of study
measure: Other efficacy assessments
timeFrame: Up to discharge/end of study
measure: Participant satisfaction assessment
timeFrame: Up to discharge/end of study
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: Bicêtre Hospital
city: Poissy
country: France
facility: Hospital Poissy
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: University Hospital Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Christophe Vayssière, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mounie M, Costa N, Gaudineau A, Molinier L, Vayssiere C, Derumeaux H. Cost-effectiveness analysis of vaginal misoprostol versus dinoprostone pessary: A non-inferiority large randomized controlled trial in France. Int J Gynaecol Obstet. 2022 Aug;158(2):390-397. doi: 10.1002/ijgo.13999. Epub 2021 Nov 19.
citation: Gaudineau A, Senat MV, Ehlinger V, Gallini A, Morin M, Olivier P, Roth E, Orusco E, Javoise S, Fort J, Lavergne C, Arnaud C, Rozenberg P, Vayssiere C; Groupe de Recherche en Obstetrique rt Gynecologie. Induction of labor at term with vaginal misoprostol or a prostaglandin E2 pessary: a noninferiority randomized controlled trial. Am J Obstet Gynecol. 2021 Nov;225(5):542.e1-542.e8. doi: 10.1016/j.ajog.2021.04.226. Epub 2021 Apr 19.