Safety and Efficacy Study of Misoprostol Vaginal Insert for Induction of Labour

Cervical Ripening Clinical Trial

Official title:

Controlled-Release Misoprostol Vaginal Insert in Parous Women for Labor Induction: Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00346840
• Other study ID #: Miso-Obs-002
• Status: Completed
• Phase: Phase 2
• First received: June 29, 2006
• Last updated: June 15, 2012
• Start date: June 2003
• Est. completion date: March 2004

Study information

• Verified date: June 2012
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was assessment of the efficacy of four dose reservoirs (25 mcg, 50 mcg, 100 mcg, 200 mcg) of intravaginal controlled release misoprostol administered for up to 24 hours. Efficacy was measured in terms of time from insert placement to vaginal delivery.

Description:

Approximately 20% of pregnant women require medical intervention to induce labour for reasons including post-date pregnancy, pre-eclampsia, maternal diabetes, premature rupture of the membranes and intra-uterine fetal growth retardation. There are two fundamental changes that characterise pre-labour preparation for delivery: sensitisation of the myometrium to produce contractions, and ripening (softening and dilation) of the cervix. Prostaglandins (PG) are fundamental to both of these changes, and several forms have been used to successfully induce labour. Dinoprostone (PGE2) is an example of a cervical ripening agent that is available in gel and tablet form and has a proven record of successful cervical ripening in this population. Dinoprostone is also available in a controlled release vaginal delivery system, which is manufactured by Controlled Therapeutics (Scotland) a subsidiary of Cytokine PharmaSciences, Inc., King of Prussia, PA, USA.

Another synthetic prostaglandin that has been shown to be an effective cervical ripener and labour inducer is misoprostol. Oral tablets are broken into fragments and used intravaginally to ripen the cervix and induce labour Due to the disadvantages of existing cervical ripeners (delivery of bolus doses, freezer or refrigerated storage, lack of efficacy in labour induction), and due to safety concerns with the off-label use of oral misoprostol tablet fragments, Controlled Therapeutics has developed a controlled release vaginal delivery system similar to its marketed dinoprostone product but containing misoprostol.

This study examines four dose strengths of the misoprostol vaginal insert in women who need to have their labours induced.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: March 2004
• Est. primary completion date: February 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At term (37 to 42 weeks inclusive gestation).

• Aged 18 years or older.

• One previous full term delivery (at least 37 weeks gestation).

• Singleton pregnancy.

• Cephalic presentation (normal lie).

• Bishop score more than 6 as determined by MBS criteria.

• Uncomplicated pregnancy as judged by the physician.

• Written informed consent.

Exclusion Criteria:

• four previous full term deliveries.

• Previous uterine surgery, including C-section and surgery to the cervix of the uterus (cone biopsy of the cervix is permitted).

• In spontaneous labour.

• Administration of oxytocin or a tocolytic drug or any other cervical ripening or labour inducing agent prior to enrolment (within seven days of enrolment).

• Suspected cephalo-pelvic disproportion.

• Evidence or suggestion of fetal distress.

• Subject has received NSAID (including aspirin) within four hours of study treatment (topical is permitted).

• Pyrexia (oral or aural temperature > 37.5C).

• Unexplained genital bleeding during this pregnancy after 24 weeks.

• Current pelvic inflammatory disease, unless adequate prior treatment has been instituted.

• Placenta praevia.

• Known or suspected allergy to misoprostol or other prostaglandins.

• Prior serious adverse event related to prostaglandin administered by any route for any indication.

• Subject unable to comply with the requirements of the protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Ripening
• Labor Induction

Intervention

Drug:
• Misoprostol vaginal insert 25 mcg
One hydrogel polymer vaginal insert for up to 24h
• Misoprostol vaginal insert 50 mcg
One hydrogel polymer vaginal insert for up to 24h
• Misoprostol vaginal insert 100 mcg
One hydrogel polymer vaginal insert for up to 24h
• Misoprostol vaginal insert 200 mcg
One hydrogel polymer vaginal insert for up to 24h

Locations

Country	Name	City	State
United Kingdom	Birmingham Women's Hospital	Birmingham
United Kingdom	Princess Royal Maternity Hospital	Glasgow
United Kingdom	King George Hospital	Ilford
United Kingdom	Liverpool Women's Hospital	Liverpool
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	The Queen's Mother's Hospital	Yorkhill, Glasgow

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Castañeda CS, Izquierdo Puente JC, Leon Ochoa RA, Plasse TF, Powers BL, Rayburn WF. Misoprostol dose selection in a controlled-release vaginal insert for induction of labor in nulliparous women. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1071-5. — View Citation

Ewert K, Powers B, Robertson S, Alfirevic Z. Controlled-release misoprostol vaginal insert in parous women for labor induction: a randomized controlled trial. Obstet Gynecol. 2006 Nov;108(5):1130-7. — View Citation

Rayburn WF, Powers BL, Plasse TF, Carr D, Di Spirito M. Pharmacokinetics of a controlled-release misoprostol vaginal insert at term. J Soc Gynecol Investig. 2006 Feb;13(2):112-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to vaginal delivery.		From insertion of study drug to neonate delivery	No
Secondary	uterine hyperstimulation		From insertion of study drug to neonate delivery	Yes
Secondary	safety in terms of maternal, fetal and neonatal adverse events		From insertion of study drug to neonate delivery	Yes
Secondary	Success on composite modified Bishop score (MBS)at 12 hours after drug insertion		From insertion of study drug to 12 hours	No
Secondary	frequency and amount of oxytocin use		From insertion of study drug to neonate delivery	No
Secondary	drug release characteristics in terms of residual concentrations		From insertion of study drug to removal of study drug	No