Comparison Between 25 µg Vaginal Misoprostol vs Slow Release Pessary PGE2 (CYTOPRO)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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 ?|
- Cesarean for all indications [ Time Frame: Up to delivery ] [ Designated as safety issue: No ]Occurrence of cesarean section for all indications
- Cost-effectiveness of two strategies (direct medical cost differential efficiency strategies measured by the Cesarean rate [ Time Frame: Up to discharge / end of study ] [ Designated as safety issue: No ]
- Adverse events [ Time Frame: Up to discharge/end of study ] [ Designated as safety issue: Yes ]Summary description of all adverse events, related adverse events and serious adverse events by treatment using MedRA classification.
- Other specific safety assessments [ Time Frame: Up to discharge/end of study ] [ Designated as safety issue: Yes ]Maternal hyperstimulation syndromes with or without changes of foetal heart rate, uterine hypertonus, rate, rate of postpartum hemorrhage, degree III/IV perineal tears, uterine rupture, neonatal rate of pH <7.05 and/or BDbase deficit> 12mmol / L, rates Apgar score <7 at 5 minutes, transfer rate in neonatal intensive-care unit (NICU), neonatal seizures
- Other efficacy assessments [ Time Frame: Up to discharge/end of study ] [ Designated as safety issue: No ]Time from 1st treatment administration to delivery, ocytocine administration and dose, occurrence of instrumental delivery, occurrence of spontaneous delivery
- Participant satisfaction assessment [ Time Frame: Up to discharge/end of study ] [ Designated as safety issue: No ]Maternal satisfaction using visual analog scale and questionnaire
|Study Start Date:||September 2012|
|Study Completion Date:||September 2015|
|Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
one 25 micrograms capsule all 4 hours by intravaginal route
administration of Misoprostol 25 micrograms capsule by intravaginal route every 4 hours, up to 4 capsules
Active Comparator: Dinoprostone
one unique intravaginal sustained released of 10 milligrams
administration of one sustained released pessary of 10 milligrams by intravaginal route
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765881
|Le Kremlin-Bicêtre, France, 94000|
|Poissy, France, 78303|
|Hôpitaux Universitaires de Strasbourg|
|Strasbourg, France, 67091|
|University Hospital Toulouse|
|Toulouse, France, 31059|
|Principal Investigator:||Christophe Vayssière, MD PhD||University Hospital, Toulouse|