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

• ClinicalTrials.gov Identifier: NCT00308711
• Recruitment Status: Completed
• First Posted: March 30, 2006
• Results First Posted: February 19, 2010
• Last Update Posted: June 25, 2012
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

Tracking Information

• First Submitted Date: March 27, 2006
• First Posted Date: March 30, 2006
• Results First Submitted Date: July 29, 2009
• Results First Posted Date: February 19, 2010
• Last Update Posted Date: June 25, 2012
• Study Start Date: April 2006
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2010)

• Minutes From Drug Insertion to Vaginal Delivery [ Time Frame: 2880 minutes ]
  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.
• Percentage of Participants With a Cesarean Section Delivery [ Time Frame: 2880 minutes ]
  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.

• Original Primary Outcome Measures (submitted: March 28, 2006): Time to vaginal delivery.

Current Secondary Outcome Measures (submitted: March 29, 2010)

• Percentage of Participants With Maternal/Fetal, Maternal (Post-Partum), and Neonatal Adverse Events [ Time Frame: 96 hours ]
  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.
• Percentage of Participants With Pre-Delivery Oxytocin Use [ Time Frame: 2880 minutes ]
  Incidence in each treatment group of need for oxytocin for pre-delivery induction or augmentation of labor.
• Percentage of Participants With Cervical Ripening Success Based On Modified Bishop Score (mBS) 12 Hours After Administration of Vaginal Insert [ Time Frame: 12 hours ]
  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.
• Minutes to Onset of Active Labor [ Time Frame: 2880 minutes ]
  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.
• Minutes to Rupture of Membranes (ROM) [ Time Frame: 2880 minutes ]
  Interval from study drug insertion to ROM.
• Duration of Stay in Minutes in Labor and Delivery Suite [ Time Frame: 5760 minuts ]
  Minutes in Labor and Delivery (L & D) suite starting from insertion of the study drug to discharge from L & D to post partum care.
• Days in Hospital for Mother and Neonate [ Time Frame: 10 days ]
  Duration of stay in hospital for mother and neonate starting with insertion of the study drug and ending with discharge from the hospital.

Original Secondary Outcome Measures (submitted: March 28, 2006)

• Incidence of adverse events (including cesarean section) and comparison of overall safety
• Need for oxytocin, duration of oxytocin use, total dose of oxytocin
• Successful cervical ripening using Modified Bishop's Score at 12 hours
• Time to onset of active labor
• Time to rupture of membranes
• Duration of stay in labor and delivery suite
• Duration of stay in hospital for mother and neonate

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety/Efficacy Study Comparing the Misoprostol Vaginal Insert to Cervidil for Cervical Ripening and Induction of Labor
• 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).
• Brief 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• 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.
  Other Name: Misopess(TM)
• 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 Name: Misopess(TM)
• 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

Study Arms

• Experimental: MVI 100
  Misoprostol vaginal insert 100 mcg over 24h
  Intervention: Drug: Misoprostol vaginal insert 100 mcg
• Experimental: MVI 50
  Misoprostol vaginal insert 50 mcg over 24h
  Intervention: Drug: Misoprostol vaginal insert 50 mcg
• Active Comparator: Cervidil 10 mg vaginal insert
  Cervidil 10 mg over 24h
  Intervention: Drug: Dinoprostone vaginal insert (Cervidil)

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2010): 1308
• Original Enrollment (submitted: March 28, 2006): 900
• Actual Study Completion Date: August 2007
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00308711
• Other Study ID Numbers: Miso-Obs-004
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ferring Pharmaceuticals
• Original Responsible Party: Not Provided
• Current Study Sponsor: Ferring Pharmaceuticals
• Original Study Sponsor: Cytokine PharmaSciences
• Collaborators: Not Provided

Investigators

• Study Director: Helen Colquhoun, MD

• PRS Account: Ferring Pharmaceuticals
• Verification Date: June 2012