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

Toulouse University Hospital

Status and phase: Completed; Phase 2

Conditions: Delivery Uterine

Treatments: Drug: Misoprostol; Drug: Dinoprostone

Study type: Interventional

Funder types: Other

Identifiers

NCT01765881

1014301

2011-000933-35 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,700 patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,700 participants in 2 patient groups

Misoprostol

Experimental group

Description:

one 25 micrograms capsule all 4 hours by intravaginal route

Treatment:

Drug: Misoprostol

Dinoprostone

Active Comparator group

Description:

one unique intravaginal sustained released of 10 milligrams

Treatment:

Drug: Dinoprostone