Safety/Efficacy Study Comparing the Misoprostol Vaginal Insert to Cervidil for Cervical Ripening and Induction of Labor

Cervical Ripening Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind Phase III Study of the Efficacy and Safety of the Misoprostol Vaginal Insert Compared to Cervidil for Women Requiring Cervical Ripening and Induction of Labor (The MVP Study).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00308711
• Other study ID #: Miso-Obs-004
• Status: Completed
• Phase: Phase 3
• First received: March 27, 2006
• Last updated: June 15, 2012
• Start date: April 2006
• Est. completion date: August 2007

Study information

• Verified date: June 2012
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the misoprostol vaginal insert (50 mcg and 100 mcg) can safely and effectively speed time to vaginal delivery compared to Cervidil (R) in women who need to have cervical ripneing and induction of labor.

Description:

Induction of labor is required in approximately 20% of pregnant women. Although contractions can be brought on by oxytocin ("pitocin"), some women need help in softening the cervix, or mouth of the womb (uterus), before oxytocin can be started. Prostaglandins have been shown to ripen, or soften, the cervix; at present, the only prostaglandin approved for marketing by FDA for this purpose is dinoprostone. Dinoprostone can be delivered in several ways; one method is to use a polymer vaginal insert that slowly releases the dinoprostone directly to the cervical tissues. This product is called Cervidil (R) and has been marketed for more than 10 years in the United States. Misoprostol is another form of prostaglandin that is approved for protecting the stomach and intestinal lining for patients taking NSAIDs. Misoprostol has also been used by many obstetricians for cervical ripening and inducing contractions, but, it is not approved by FDA for this purpose.

The same company that makes the Cervidil polymer insert has made an insert that will slowly release misoprostol. This study will determine whether this investigational insert containing misoprostol will decrease time to vaginal delivery compared to Cervidil. Two different doses of misoprostol will be tested (50 micrograms and 100 micrograms); each vaginal insert will gradually release a small, controlled amount of misoprostol over up to 24 hours.

Comparator: The Cervidil (R) vaginal insert containing dinoprostone will be the comparator in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1308
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnant women at least 36 weeks gestation requiring cervical ripening and induction of labor

Exclusion Criteria:

• No uterine scar (no previous delivery by cesarean section)

• No multiple gestation

• No condition that disallows use of prostaglandins for induction of labor

• No more than 3 previous vaginal births beyond 24 weeks gestation

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, Induced

Intervention

Drug:
• Misoprostol vaginal insert 100 mcg
Hydrogel polymer intravaginal insert with retrieval system. One insert is to remain in the posterior fornix of the vagina until removed for one of the following conditions: onset of active labor; maternal/fetal complication, e.g. non-reassuring fetal heart rate. Record if the insert falls out prior to meeting one of the first two criteria. In no case is the insert to remain in place longer than 24h.
• Misoprostol vaginal insert 50 mcg
Hydrogel polymer intravaginal insert with retrieval system. One insert is to remain in the posterior fornix of the vagina until removed for one of the following conditions: onset of active labor; maternal/fetal complication, e.g. non-reassuring fetal heart rate. Record if the insert falls out prior to meeting one of the first two criteria. In no case is the insert to remain in place longer than 24h.
• Dinoprostone vaginal insert (Cervidil)
Hydrogel polymer intravaginal insert with retrieval system. One insert is to remain in the posterior fornix of the vagina until removed for one of the following conditions: onset of active labor; maternal/fetal complication, e.g. non-reassuring fetal heart rate. Record if the insert falls out prior to meeting one of the first two criteria. In no case is the insert to remain in place longer than 24h.

Locations

Country	Name	City	State
Canada	IWK Health Centre and Dalhousie University	Halifax	Nova Scotia
Canada	University of Saskatchewan Royal University Hospital	Saskatoon	Saskatchewan
Canada	Women's Health Centre/General Hospital/Eastern Health	St. John's	Newfoundland and Labrador
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	University of New Mexico Medical Center	Albuquerque	New Mexico
United States	Lehigh Valley Medical Center	Allentown	Pennsylvania
United States	Northside Hospital	Alpharetta	Georgia
United States	Overlake Hospital Medical Center	Bellevue	Washington
United States	University of Alabama at Birmingham Medical Center	Birmingham	Alabama
United States	Jacobi Medical Center	Bronx	New York
United States	Erlanger Hospital	Chattanooga	Tennessee
United States	University of Cincinnati Holmes Hospital	Cincinnati	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Methodist Charlton Medical Center	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Hurley Medical Center	Flint	Michigan
United States	Greenville Hospital System	Greenville	South Carolina
United States	University of Texas Health Sciences Center at Houston	Houston	Texas
United States	United Health Services Hospitals, Inc.	Johnson City	New York
United States	University of Tennesse Medical Center	Knoxville	Tennessee
United States	St. Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Baptist Memorial Hospital	Memphis	Tennessee
United States	Banner Desert Medical Center	Mesa	Arizona
United States	Winthrop-South Nassau University Health Center	Mineola	New York
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	NYU School of Medicine	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	Trident Health System	North Charleston	South Carolina
United States	McKay-Dee Hospital	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UCI Medical Center	Orange	California
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Arizona Wellness Center for Women	Phoenix	Arizona
United States	Maricopa Medical Center	Phoenix	Arizona
United States	University of Pittsburgh - Magee Women's Hospital	Pittsburgh	Pennsylvania
United States	Legacy Center for Maternal-Fetal Medicine	Portland	Oregon
United States	St. Mark's Hospital	Salt Lake City	Utah
United States	University of Utah Health Science Center	Salt Lake City	Utah
United States	Santa Clara Valley Medical Center	San Jose	California
United States	Bayfront Medical Center	St. Petersburg	Florida
United States	University of Florida Health Sciences Center	Tampa	Florida
United States	Kings Daughters Clinic	Temple	Texas
United States	Tuscon Medical Center	Tucson	Arizona
United States	Jordan Valley Hospital	West Jordan	Utah
United States	St. Mary's Medical Center	West Palm Beach	Florida
United States	Pioneer Valley Hospital	West Valley City	Utah
United States	Saint Clare's Hospital	Weston	Wisconsin
United States	Women's Health Alliance	Winston-Salem	North Carolina
United States	Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

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

Pevzner L, Rayburn WF, Rumney P, Wing DA. Factors predicting successful labor induction with dinoprostone and misoprostol vaginal inserts. Obstet Gynecol. 2009 Aug;114(2 Pt 1):261-7. doi: 10.1097/AOG.0b013e3181ad9377. — 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

Wing DA; Misoprostol Vaginal Insert Consortium. Misoprostol vaginal insert compared with dinoprostone vaginal insert: a randomized controlled trial. Obstet Gynecol. 2008 Oct;112(4):801-12. doi: 10.1097/AOG.0b013e318187042e. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Minutes From Drug Insertion to Vaginal Delivery	Interval between time/date of insertion of study drug and time/date of neonate birth. This is a time-to-event analysis, there is no set time for the assessment. The endpoint occurs when the baby is born. 48 hours can be used as an approximate interval by which time most of the babies have been delivered.	2880 minutes	No
Primary	Percentage of Participants With a Cesarean Section Delivery	Percentage of participants with cesarean delivery after study drug was administered. There is no set assessment time or date as the woman's labor may last hours or days.	2880 minutes	Yes
Secondary	Percentage of Participants With Maternal/Fetal, Maternal (Post-Partum), and Neonatal Adverse Events	This outcome reports the percentage of adverse events in each treatment arm spontaneously reported or observed during the study. The intrapartum period (mother is still pregnant) is called the "Maternal/Fetal" period; once the baby has been born, adverse events are assessed separately for the mother (Post Partum) and the baby (Neonatal). The number of adverse events was assessed separately for each of the three periods.	96 hours	Yes
Secondary	Percentage of Participants With Pre-Delivery Oxytocin Use	Incidence in each treatment group of need for oxytocin for pre-delivery induction or augmentation of labor.	2880 minutes	No
Secondary	Percentage of Participants With Cervical Ripening Success Based On Modified Bishop Score (mBS) 12 Hours After Administration of Vaginal Insert	Measured the percentage of participants who achieved success on the mBS. This composite score is based on the mBS and vaginal delivery and it is measured 12 hours after insertion of the study drug. The mBS has a score of 0 when the cervix is not ripe and a score of 12 when completely ripened. The 12 hour score is compared to baseline. Using the mBS, assess at 12 hours whether each subject has met any of the following three criteria: 1) has improved (increased) the mBS by at least 3 points from baseline; 2) has reached a score of at least 6 on the mBS; or 3) has acheived a vaginal delivery.	12 hours	No
Secondary	Minutes to Onset of Active Labor	Interval from insertion of study drug to onset of active labor, defined as at least three contractions in a ten-minute period of at least moderate intensity and resulting in cervical change such as dilatation or effacement; OR at least 4 cm cervical dilatation achieved after progressive change in dilatation.	2880 minutes	No
Secondary	Minutes to Rupture of Membranes (ROM)	Interval from study drug insertion to ROM.	2880 minutes	No
Secondary	Duration of Stay in Minutes in Labor and Delivery Suite	Minutes in Labor and Delivery (L & D) suite starting from insertion of the study drug to discharge from L & D to post partum care.	5760 minuts	No
Secondary	Days in Hospital for Mother and Neonate	Duration of stay in hospital for mother and neonate starting with insertion of the study drug and ending with discharge from the hospital.	10 days	No