CYTOPRO: Comparison Between 25 µg Vaginal Misoprostol vs Slow Release Pessary PGE2

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT01765881

Collaborator

(none)

1,700

Enrollment

Locations

Arms

Duration (Months)

425

Patients Per Site

11.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Delivery Uterine	Drug: Misoprostol Drug: Dinoprostone	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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 ?

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Misoprostol one 25 micrograms capsule all 4 hours by intravaginal route	Drug: Misoprostol administration of Misoprostol 25 micrograms capsule by intravaginal route every 4 hours, up to 4 capsules Other Names: CYTOTEC 25 micrograms Misoprostol capsule by intravaginal route
Active Comparator: Dinoprostone one unique intravaginal sustained released of 10 milligrams	Drug: Dinoprostone administration of one sustained released pessary of 10 milligrams by intravaginal route Other Names: PROPESS one intravaginal sustained released capsule of 10 milligrams

Arm

Intervention/Treatment

Experimental: Misoprostol

one 25 micrograms capsule all 4 hours by intravaginal route

Drug: Misoprostol

administration of Misoprostol 25 micrograms capsule by intravaginal route every 4 hours, up to 4 capsules

Other Names:

CYTOTEC

25 micrograms Misoprostol capsule by intravaginal route

Active Comparator: Dinoprostone

one unique intravaginal sustained released of 10 milligrams

Drug: Dinoprostone

administration of one sustained released pessary of 10 milligrams by intravaginal route

Other Names:

PROPESS

one intravaginal sustained released capsule of 10 milligrams

Outcome Measures

Primary Outcome Measures

Cesarean for all indications [Up to delivery]
Occurrence of cesarean section for all indications

Secondary Outcome Measures

Cost-effectiveness of two strategies (direct medical cost differential efficiency strategies measured by the Cesarean rate [Up to discharge / end of study]

Other Outcome Measures

Adverse events [Up to discharge/end of study]
Summary description of all adverse events, related adverse events and serious adverse events by treatment using MedRA classification.
Other specific safety assessments [Up to discharge/end of study]
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 [Up to discharge/end of study]
Time from 1st treatment administration to delivery, ocytocine administration and dose, occurrence of instrumental delivery, occurrence of spontaneous delivery
Participant satisfaction assessment [Up to discharge/end of study]
Maternal satisfaction using visual analog scale and questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Bicêtre Hospital	Le Kremlin-Bicêtre	France	94000
2	Hospital Poissy	Poissy	France	78303
3	Hôpitaux Universitaires de Strasbourg	Strasbourg	France	67091
4	University Hospital Toulouse	Toulouse	France	31059