Induction of Labor by Oral Misoprostol Solution (OMS)

A Randomised Control Study of Titrated and Static Oral Misoprostol for Induction of Labor at Term

AIM: To evaluate effectiveness and safety of titrated oral misoprostol solution (OMS) in comparison with static-dose oral misoprostol solution for induction of labor at term.

Women with singleton live pregnancy at term without any complications who were admitted in labor room for induction of labor were enrolled.

Study involves allocation of selected women in two groups randomly and use of either titrated or static oral misoprostol dose regimen to induce labor. Possible benefits included rapid induction of labor with oral drug regimen which is easier to comply as compared to vaginal regimens. Women were at risk of all the complications associated with induction of labor like labor abnormalities, risk of cesarean section, non reassuring fetal status.

Study Overview

• Status: Completed
• Conditions: Induction of Labor
• Intervention / Treatment: Drug: Oral misoprostol solution (OMS)

Detailed Description

This comparative randomized study was conducted in the Department of Obstetrics and Gynecology, Christian medical college and hospital, Ludhiana for a period of one year beginning from 1st December, 2017 to 30th November, 2018. The study group comprised of all antenatal women admitted in labor room at term for induction of labor. Informed consent was taken for all selected women. Women were subjected to detailed history taking, a complete physical examination including per vaginum examination (to calculate modified bishop's score and to rule out cephalopelvic disproportion), investigations and a NST. Gestational age was established by the first date of the last menstrual period and confirmed by first trimester ultrasound. Presentation was confirmed by palpation and third trimester ultrasound.

Women after randomization were allocated into two groups. The first group (A) was induced with hourly titrated oral misoprostol regimen and the second group (B) received two hourly static oral misoprostol regimen. Once labor had started, vital signs were closely monitored every 2 hours; fetal heart rate (FHR) and uterine activity every 15 minutes during first stage of labor. Per vaginum examination was done 4-hourly or as indicated.

Primary and secondary outcome measures were noted and analyzed to compare safety and efficacy of titrated and oral misoprstol solution.

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Punjab
    • Ludhiana, Punjab, India, 141008
      • Christian Medical College and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Singleton live pregnancy;
2. ≥37 weeks gestation;
3. Cephalic presentation;
4. Reassuring fetal heart rate;
5. Modified Bishop'score

Exclusion Criteria:

1. Hypersensitivity to misoprostol;
2. Uterine scar due to previous cesarean section or other uterine surgery;
3. Grand multipara;
4. Multiple gestations;
5. High risk pregnanacies • preeeclampsia with severe features • significant maternal cardiac,renal, liver disease
6. Any contraindication to induction and vaginal delivery e.g. cephalopelvic disproportion, malpresentation, fetal compromise and ante partum hemorrhage
7. Intrauterine fetal demise

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (Titrated OMS); Titrated oral misoprostol solution	Drug: Oral misoprostol solution (OMS); Based on the WHO labor induction recommendation, and for the purpose of achieving precise oral misoprostol dosage, one misoprostol tablet (200 mcg) was pulverized and dissolved into 200 ml water.90 Thus 1ml of solution had 1mcg of misoprostol. This misoprostol solution could be preserved at room temperature and remained active for 24 hours. Hourly titrated oral misoprostol solution was given to group A as described by Wang X et al, 2016 as described below. 0 hour= 20ml; hour= 20ml; hour= 30ml; hour= 30ml; hour= 30ml; hour= 40ml 6.5 hour= 50ml 8.5 hour= 60ml 10.5 hour=60ml Group B received 25 mcg (25 ml) oral misoprostol solution every 2 hours for a maximum of 12 doses or until the onset of regular uterine activity.
Active Comparator: Group B (Static OMS); Static oral misoprostol solution	Drug: Oral misoprostol solution (OMS); Based on the WHO labor induction recommendation, and for the purpose of achieving precise oral misoprostol dosage, one misoprostol tablet (200 mcg) was pulverized and dissolved into 200 ml water.90 Thus 1ml of solution had 1mcg of misoprostol. This misoprostol solution could be preserved at room temperature and remained active for 24 hours. Hourly titrated oral misoprostol solution was given to group A as described by Wang X et al, 2016 as described below. 0 hour= 20ml; hour= 20ml; hour= 30ml; hour= 30ml; hour= 30ml; hour= 40ml 6.5 hour= 50ml 8.5 hour= 60ml 10.5 hour=60ml Group B received 25 mcg (25 ml) oral misoprostol solution every 2 hours for a maximum of 12 doses or until the onset of regular uterine activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interval between induction and delivery	The time taken from induction of labor to delivery measured as 1) <12 hours 2) 12-24 hours 3) 24-48 hours 4) >48 hours	From first dose of oral misoprostol solution (titrated/static) to childbirth; upto 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in modified Bishop's score	Measured as difference between modified bishop's score before induction of labor and at amniotomy/stopping of oral misoprostol solution regimen; minimum 0f 1 to maximum of 7.	From first dose of oral misoprostol solution to childbirth (intrapartum); upto 5 days
Number of misoprostol doses	Measured as 1-2; 3-4; 5-6; 7-8; >9	From first dose of oral misoprostol solution to childbirth (intrapartum); upto 5 days
Time taken to give required doses	Measured as 1-4 hours; 5-8 hours; 9-12 hours; 13-16 hours; 17-20 hours; 21-24 hours	From first dose of oral misoprostol solution to childbirth (intrapartum); upto 5 days
Total misoprostol dosage	Measured as </=75mcg; 76-150mcg; 151-225mcg; 226-300mcg; >301 mcg	From first dose of oral misoprostol solution to childbirth (intrapartum); upto 5 days
Mode of delivery	In terms of Vaginal delivery/LSCS	Upto 5 days from first dose of oral misoprostol solution
Indication for LSCS	Divided into either of the following: SECONDARY ARREST OF DILATATION; MSAF IN EARLY LABOR; CTG CATEGORY III; FAILED INDUCTION; CEPHALOPELVIC DISPROPORTION; CORD PROLAPSE; DEEP TRANSVERSE ARREST; ARREST OF DESCENT OF HEAD	Upto 5 days from first dose of oral misoprostol solution
Oxytocin augmentation	Required/Not required	From first dose of oral misoprostol solution to childbirth (intrapartum); upto 5 days
Maternal morbidity	In terms of incidence of either of the following: Incidence of tachysystole; Fever- intrapartum and postpartum; Puerperal sepsis; Uterine rupture	From first dose of oral misoprostol solution to dischage from hospital; upto 7 days
Neonatal parameters	Measured in terms of incidence of either of the following: Incidence of meconium-stained liquor; APGAR scores at 1,5 min; NICU stay	From childbirth to discharge of the baby; upto 1 month

Collaborators and Investigators

• Sponsor: Christian Medical College and Hospital, Ludhiana, India
• Investigators: Study Chair: SUNITA GOYAL, MBBS, MD, Department of obstetrics and gynecology, Christian Medical College and hospital, Ludhiana

Publications and helpful links

General Publications

• Rouzi AA, Alsahly N, Alamoudi R, Almansouri N, Alsinani N, Alkafy S, Rozzah R, Abduljabbar H. Randomized clinical trial between hourly titrated and 2 hourly static oral misoprostol solution for induction of labor. Am J Obstet Gynecol. 2017 Apr;216(4):405.e1-405.e6. doi: 10.1016/j.ajog.2016.11.1054. Epub 2016 Dec 14.
• Aduloju OP, Ipinnimo OM, Aduloju T. Oral misoprostol for induction of labor at term: a randomized controlled trial of hourly titrated and 2 hourly static oral misoprostol solution. J Matern Fetal Neonatal Med. 2021 Feb;34(4):493-499. doi: 10.1080/14767058.2019.1610378. Epub 2019 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: May 13, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• 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: Titrated and Static OMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD that underlie the results reported in the study, after deidentification (text, tables, figures and appendices) will be shared in the excel sheet format.
• IPD Sharing Time Frame: Data will be available beginning immediately and ending 36 months following article publication.
• IPD Sharing Access Criteria: Anyone who wishes to access the data for any purpose. Link will be made available at a later date.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Study Data/Documents

1. Informed Consent Form
   Information identifier: PATIENT INFORMATION SHEET
2. Study Protocol
   Information identifier: STUDY PROTOCOL

Drug and device information, study documents

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