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

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).

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.

Study Overview

• Status: Completed
• Conditions: Labor, Induced; Cervical Ripening
• Intervention / Treatment: Drug: Misoprostol vaginal insert 100 mcg; Drug: Misoprostol vaginal insert 50 mcg; Drug: Dinoprostone vaginal insert (Cervidil)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 1308
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Women's Health Centre/General Hospital/Eastern Health
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre and Dalhousie University
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • University of Saskatchewan Royal University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham Medical Center
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Banner Desert Medical Center
    • Phoenix, Arizona, United States, 85008
      • Maricopa Medical Center
    • Phoenix, Arizona, United States, 85032
      • Arizona Wellness Center for Women
    • Tucson, Arizona, United States, 85716
      • Tuscon Medical Center
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Orange, California, United States, 92868
      • UCI Medical Center
    • San Jose, California, United States, 95128
      • Santa Clara Valley Medical Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Bayfront Medical Center
    • Tampa, Florida, United States, 33606
      • University of Florida Health Sciences Center
    • West Palm Beach, Florida, United States, 33401
      • St. Mary's Medical Center
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Northside Hospital
  • Michigan
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • St. Elizabeth Regional Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Medical Center
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Johnson City, New York, United States, 13790
      • United Health Services Hospitals, Inc.
    • Mineola, New York, United States, 11501
      • Winthrop-South Nassau University Health Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • NYU School of Medicine
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Women's Health Alliance
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Holmes Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97232
      • Legacy Center for Maternal-Fetal Medicine
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19090
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh - Magee Women's Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
    • North Charleston, South Carolina, United States, 29406
      • Trident Health System
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Hospital
    • Knoxville, Tennessee, United States, 37920
      • University of Tennesse Medical Center
    • Memphis, Tennessee, United States, 38119
      • Baptist Memorial Hospital
  • Texas
    • Dallas, Texas, United States, 75327
      • Methodist Charlton Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences Center at Houston
    • Temple, Texas, United States, 76502
      • Kings Daughters Clinic
  • Utah
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital
    • Salt Lake City, Utah, United States, 84124
      • St. Mark's Hospital
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Science Center
    • West Jordan, Utah, United States, 84088
      • Jordan Valley Hospital
    • West Valley City, Utah, United States, 84120
      • Pioneer Valley Hospital
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Hospital Medical Center
  • Wisconsin
    • Weston, Wisconsin, United States, 54476
      • Saint Clare'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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MVI 100; Misoprostol vaginal insert 100 mcg over 24h	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.; Other Names: Misopess(TM)
Experimental: MVI 50; Misoprostol vaginal insert 50 mcg over 24h	Drug: 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.; Other Names: Misopess(TM)
Active Comparator: Cervidil 10 mg vaginal insert; Cervidil 10 mg over 24h	Drug: 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.; Other Names: Propess(R); 10 mg dinoprostone vaginal insert

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Minutes to Rupture of Membranes (ROM)	Interval from study drug insertion to ROM.	2880 minutes
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
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

Collaborators and Investigators

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

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.
• 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.
• 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):261-267. doi: 10.1097/AOG.0b013e3181ad9377.
• Hawkins JS, Stephenson M, Powers B, Wing DA. Diabetes mellitus: an independent predictor of duration of prostaglandin labor induction. J Perinatol. 2017 May;37(5):488-491. doi: 10.1038/jp.2016.270. Epub 2017 Jan 26.
• Brennan MC, Pevzner L, Wing DA, Powers BL, Rayburn WF. Retention of dinoprostone vaginal insert beyond 12 hours for induction of labor. Am J Perinatol. 2011 Jun;28(6):479-84. doi: 10.1055/s-0030-1271208. Epub 2011 Jan 11.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: March 27, 2006
• First Submitted That Met QC Criteria: March 28, 2006
• First Posted (Estimate): March 30, 2006

Study Record Updates

• Last Update Posted (Estimate): June 25, 2012
• Last Update Submitted That Met QC Criteria: June 15, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Cesarean section; Induction of labor; Cervical ripening; Dinoprostone vaginal insert; Cervidil; Misoprostol vaginal insert; Modified Bishop's Score; PGE2; PGE1; Uterine Hyperstimulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol; Dinoprostone
• Other Study ID Numbers: Miso-Obs-004