Comparison of Misoprostol Ripening Efficacy With Dilapan (COMRED)

Dilapan vs Misoprostol for Cervical Ripening [COMRED - Comparison of Misoprostol Ripening Efficacy With Dilapan]

The purpose of this study is to find out if Dilapan works as well as Misoprostol for preparing the mouth of the uterus (cervix) for inducing labor in women who need to undergo this procedure. The primary objective is to assess the efficacy of Dilapan for cervical ripening compared to Misoprostol in women undergoing Induction of labor (IOL) at or more than 37 weeks gestation.

Study Overview

• Status: Completed
• Conditions: Labor Onset and Length Abnormalities; Induced; Birth
• Intervention / Treatment: Device: Dilapan; Drug: Misoprostol

Detailed Description

In developed nations 25 % of pregnant women undergo labor induction for various indications. Likelihood of vaginal delivery depends on the degree of ripeness of cervix. Majority of women undergoing induction of labor are candidates for cervical ripening. Dilapan is an osmotic hygroscopic dilator of cervix commonly used for cervical preparation for mid trimester abortions. It has been proven safe for use for induction of Labor (IOL) at term. Misoprostol is a synthetic prostaglandin E1 analogue, widely used for cervical ripening and IOL in United States and is considered as standard of care.

This is a non-inferiority, unblinded randomized, controlled trial where 322 eligible participants undergoing IOL at >37 weeks gestation and admitted to labor and delivery unit will be enrolled and randomly assigned in a ratio 1:1 to either receive Dilapan or Misoprostol for cervical ripening.

After randomization all participants will undergo assessment as per standard of care. Participants will have either 1-5 Dilapan rods inserted into their cervix by the providers or receive 25 mcg of misoprostol orally every 2 hours to a maximum of 6 doses over 12 hours. Participants will be evaluated for artificial rupture of membranes and initiation of oxytocin for inducing uterine contraction. A diagnosis of failed IOL will be made if patient does not go into active labor within 24 hours after initiation of Oxytocin and Artificial Rupture Of Membranes (AROM). Intrapartum management will be according to institutional guidelines. All participants will be followed up and contacted by phone 2 weeks after discharge regarding their experience with the method of induction.

• Study Type: Interventional
• Enrollment (Actual): 308
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10034
      • New York Presbyterian - Allen Hospital
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women undergoing labor induction with a gestation of ≥37 weeks (based on a sure last menstrual period and an ultrasound done before 22 0/7 weeks)
2. Live fetus with in cephalic presentation
3. Singleton pregnancy
4. Able to provide informed consent for participation in the study

Exclusion Criteria:

1. Contraindication for vaginal delivery
2. Age less than 18 years
3. Prior uterine scar from a cesarean section or myomectomy
4. Patients who have HELLP syndrome or eclampsia
5. Active genital herpes at the time of labor induction
6. Complex medical problems that may require assistance with second stage of labor
7. Bishop score ≥ 6
8. Major fetal congenital anomalies (as assessed by investigator)
9. Premature rupture of membranes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dilapan group; Patients who are randomized to receive Dilapan, will have 3-5 rods of Dilapan-S® inserted in their cervix by the supervising provider, under aseptic precautions with a speculum exam, either digitally or using a sponge forceps, as per manufacturer's recommendations. The Bishop score at the time of eligibility assessment and number of rods inserted will be recorded. Dilapan will be left in cervix for 12 hours. Patients will be allowed to ambulate, shower and have light meals as long as they meet the criteria based on institutional guidelines for intermittent fetal heart monitoring. "Nothing per vagina" including douching and no bathing is allowed.	Device: Dilapan; Dilapan-S® is a mechanical method for cervical ripening using rods made of a patented hydrogel Aquacryl, it is marketed in form of rods of 3 and 4 mm diameter. It is FDA approved for cervical ripening.; Other Names: Aquacryl Hydrogel
EXPERIMENTAL: Misoprostol group; Patients who are randomized to Misoprostol group, after the baseline assessment and a reassuring cardiotocograms (CTG) monitoring for 20 minutes to a maximum of 6 doses. All subjects will have continuous fetal monitoring. A dose will be held if patient is noted to have uterine tachysystole, hyperstimulation, fetal heart tracing abnormalities or 3 or more painful uterine contractions over a period of 10 minutes (indicating onset of labor). Administration of Misoprostol will be done by the nurse assigned to the patient.	Drug: Misoprostol; 25mcg of Misoprostol will be administered orally every 2 hours (maximum of 6 doses) Misoprostol is a prostaglandin E1 analog approved for treatment and prevention of gastric ulcers. The use of Misoprostol appears to be safe and effective for induction of labor when used in low dose.; Other Names: Cytotec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of women achieving vaginal delivery	This is to measure the efficacy of either Dilapan or Misoprostol for cervical ripening	Up to 36 hours after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bishop score	The Bishop Score (also known as Pelvic Score) is the most commonly used method to rate the readiness of the cervix for induction of labor. The Bishop Score gives points to 5 measurements of the pelvic examination dilation, effacement of the cervix, station of the fetus, consistency of the cervix, and position of the cervix. It ranges from 0 to 13. Higher score is associated with increased likelihood of vaginal delivery.	At 12 hours after intervention
Percentage of women delivering vaginally in 24 hours after the initiation of intervention	This is to measure the efficacy of either Dilapan or Misoprostol for cervical ripening	Up to 24 hours after intervention
Overall vaginal delivery rate	This is to measure the efficacy of either Dilapan or Misoprostol for cervical ripening	Approximately up to 48 hours
Rate of cesarean deliveries	This is to measure the efficacy of either Dilapan or Misoprostol for cervical ripening	Approximately up to 48 hours
Total length of hospital stay	This is to measure the cost-effectiveness of either Dilapan or Misoprostol for cervical ripening. Length will be measured in number of days from hospital admission until discharge.	Up to 4 days
Percentage of women who developed chorioamnionitis	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening	From delivery until two weeks after discharge (approximately up to 3 weeks)
Percentage of women who developed endometritis within 14 days of intervention	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening	From delivery until two weeks after discharge (approximately up to 3 weeks)
Percentage of women who developed postpartum hemorrhage	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening, postpartum hemorrhage is defined as estimated blood loss (EBL) > 1000cc and/or drop in Hematocrit (HCT) by 10 points.	From delivery until two weeks after discharge (approximately up to 3 weeks)
Percentage of newborns with Apgar score <7 at 5 min	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening by studying the effect on newborns	From birth until two weeks after birth
Percentage of newborns with cord arterial blood potential hydrogen (pH) < 7	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening by studying the effect on newborns	From birth until two weeks after birth
Percentage of newborns with neonatal intensive care unit (NICU) admission within 14 days after study intervention	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening by studying the effect on newborns	From birth until two weeks after birth
Percentage of newborns with antibiotic use within 14 days after study intervention	This is to measure the safety of either Dilapan or Misoprostol for cervical ripening by studying the effect on newborns	From birth until two weeks after birth

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Medicem International CR s.r.o.
• Investigators: Principal Investigator: Rachana Gavara, MD, rg2460@cumc.columbia.edu

Publications and helpful links

General Publications

• Gavara R, Saad AF, Wapner RJ, Saade G, Fu A, Barrow R, Nalgonda S, Bousleiman S, Almonte C, Alnafisee S, Holman A, Burgansky A, Heikkila P. Cervical Ripening Efficacy of Synthetic Osmotic Cervical Dilator Compared With Oral Misoprostol at Term: A Randomized Controlled Trial. Obstet Gynecol. 2022 Jun 1;139(6):1083-1091. doi: 10.1097/AOG.0000000000004799. Epub 2022 May 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2018
• Primary Completion (ACTUAL): July 21, 2021
• Study Completion (ACTUAL): July 21, 2021

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (ACTUAL): September 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Induction of labor; Misoprostol; Dilapan; Aquacryl hydrogel
• Additional Relevant MeSH Terms: Congenital Abnormalities; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: AAAR8566

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No