Induction of Labor by Oral Misoprostol Solution

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Induction of Labor

Intervention / Treatment
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* Drug: Oral misoprostol solution (OMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton live pregnancy; ≥37 weeks gestation; Cephalic presentation; Reassuring fetal heart rate; Modified Bishop'score Exclusion Criteria: Hypersensitivity to misoprostol; Uterine scar due to previous cesarean section or other uterine surgery; Grand multipara; Multiple gestations; High risk pregnanacies • preeeclampsia with severe features • significant maternal cardiac,renal, liver disease Any contraindication to induction and vaginal delivery e.g. cephalopelvic disproportion, malpresentation, fetal compromise and ante partum hemorrhage Intrauterine fetal demise

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single center interventional single-blinded randomised controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A (Titrated OMS)<br>Titrated oral misoprostol solution | Drug: Oral misoprostol solution (OMS)<br>* 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.<br>|
| Active Comparator: Group B (Static OMS)<br>Static oral misoprostol solution | Drug: Oral misoprostol solution (OMS)<br>* 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.<br>|

What is the study measuring?
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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 |