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

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Ripening; Labor Induction
• Intervention / Treatment: Drug: Misoprostol vaginal insert 25 mcg; Drug: Misoprostol vaginal insert 50 mcg; Drug: Misoprostol vaginal insert 100 mcg; Drug: Misoprostol vaginal insert 200 mcg

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B13 9HP
    • Birmingham Women's Hospital
  • Glasgow, United Kingdom, G11 5DY
    • Princess Royal Maternity Hospital
  • Ilford, United Kingdom, IG3 8YB
    • King George Hospital
  • Liverpool, United Kingdom, L8 7SS
    • Liverpool Women's Hospital
  • Northampton, United Kingdom, NN1 5BD
    • Northampton General Hospital
  • Yorkhill, Glasgow, United Kingdom, G12 9TZ
    • The Queen's Mother's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MVI 25; Misoprostol vaginal insert 25 mcg	Drug: Misoprostol vaginal insert 25 mcg; One hydrogel polymer vaginal insert for up to 24h; Other Names: Misoprostol vaginal insert
Experimental: MVI 50; Misoprostol vaginal insert 50 mcg	Drug: Misoprostol vaginal insert 50 mcg; One hydrogel polymer vaginal insert for up to 24h; Other Names: Misoprostol vaginal insert
Experimental: MVI 100; Misoprostol vaginal insert 100 mcg	Drug: Misoprostol vaginal insert 100 mcg; One hydrogel polymer vaginal insert for up to 24h; Other Names: Misoprostol vaginal insert
Experimental: MVI 200; Misoprostol vaginal insert 200 mcg	Drug: Misoprostol vaginal insert 200 mcg; One hydrogel polymer vaginal insert for up to 24h; Other Names: Misoprostol vaginal insert

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to vaginal delivery.	From insertion of study drug to neonate delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
uterine hyperstimulation	From insertion of study drug to neonate delivery
safety in terms of maternal, fetal and neonatal adverse events	From insertion of study drug to neonate delivery
Success on composite modified Bishop score (MBS)at 12 hours after drug insertion	From insertion of study drug to 12 hours
frequency and amount of oxytocin use	From insertion of study drug to neonate delivery
drug release characteristics in terms of residual concentrations	From insertion of study drug to removal of study drug

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Helen Colquhoun, MD, Pleiad, Inc.

Publications and helpful links

General Publications

• Castaneda 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. doi: 10.1016/j.ajog.2005.06.072.
• 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. doi: 10.1016/j.jsgi.2005.10.004.
• 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. doi: 10.1097/01.AOG.0000239100.16166.5a.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): February 1, 2004
• Study Completion (Actual): March 1, 2004

Study Registration Dates

• First Submitted: June 29, 2006
• First Submitted That Met QC Criteria: June 29, 2006
• First Posted (Estimate): June 30, 2006

Study Record Updates

• Last Update Posted (Estimate): June 18, 2012
• Last Update Submitted That Met QC Criteria: June 15, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: misoprostol; cervical ripening; Labor induction; vaginal insert
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: Miso-Obs-002