Induction of Labor in Pregnant Women With Prelabor Rupture of Membranes - Oxytocin or Misoprostol

Oxytocin Versus Oral Misoprostol for Induction of Labor in Pregnant Women With Term Prelabor Rupture of Membranes

The aim of study is to compare the efficacy and safety of oral misoprostol versus oxytocin in induction of labor in pregnant women with prelabor rupture of membranes at term.

Study Overview

• Status: Completed
• Conditions: Prelabor Rupture of Membranes
• Intervention / Treatment: Drug: Misoprostol; Drug: Syntocinon

Detailed Description

Type of Study: Randomized controlled clinical trial. Study Setting: The study will be conducted at Ain Shams University Maternity Hospital (ASUMH) at labor ward.

Study Population: pregnant women attending at Ain Shams University Maternity Hospital for induction of labor at term

Sample Size: The study will be conducted on (170) women; they will be subdivided into 2 groups.

• 1st group (misoprostol group): induction of labor by 25µg misoprostol oral tablet every 4 hours with maximum200 µg.
• 2nd group (oxytocin group:control group): induction of labor done by administration of oxytocin infusion according to ASUMH local protocol.
• Sample size Justification: Using PASS 11program for sample size calculation and according to (Zeteroğlu S et al, 2006), the expected mean interval from induction to delivery in misoprostol group=10.61 ± 2.45 hours and oxytocin group=11.57 ± 1.91 hours. Sample size of 85 women per group can detect the difference between two group with power80% setting alpha error at 0.05.

Study procedures and interventions:

1. After approval of study protocol; pregnant women attending Ain Shams University Maternity Hospital for induction of labor will be enrolled into the study according to inclusion and exclusion criteria.

2. History taking, examination and investigation will be done to choose eligible patients.

   History: personal, obstetric history, past history (any medical or surgical disorder)

   Examination:

   General: pulse, blood pressure, temperature. Abdominal: size of the uterus, previous scar, presentation Per vaginal examination (PV): assessment of Bishop Score. Investigations: Routine laboratory: (CBC, Urine analysis, blood group and Rh typing) and ultrasound for (viability of fetus, fetal biometry and estimated fetal weight, amniotic fluid, placental localization), admission fetal heart rate (FHR) assessment (non-stress test "NST")

3. Eligible patients will be randomized using a computer-generated sequence 1:1 either to the misoprostol group or to oxytocin group.

The supervisor will do all procedures. Randomization: Will be done using computer generated randomization sheet using Med calc. ©.

Allocation and concealment: will be done using sealed opaque envelopes. Each woman will be invited to pull out an envelope, and according to the letter within she will be allocated to either group (group A: oral misoprostol; group B: oxytocin group) 4. Intervention:

1. st group (Misoprostol group): induction of labor by 25µg misoprostol oral tablet every 4 hours maximum200 µg.( Alfirevic Z et al., 2014)
2. nd group (Oxytocin group): oxytocin infusion according to ASUMH oxytocin protocol.

Syntocinon Mix: {if patient fit for induction} Put 3 international units "IU" oxytocin (3000mIU) +50ml of normal saline in syringe pump= (60mIU/ml).

Commence at 1ml/hour (1mIU/min) for 1/2 hour.

• If contractions inadequate +fetal monitor healthy 2 ml/hour for 1/2 hour.
• If contractions inadequate +fetal monitor healthy 4 ml/hour for 1/2 hour.
• If contractions inadequate +fetal monitor healthy 6 ml/hour for 1/2 hour.
• If contractions inadequate +fetal monitor healthy increase by 2ml/hr. for max. 27ml/hour.

At any point there's fetal or maternal distress (e.g. pathological FHR pattern, antepartum hemorrhage, etc.) the study intervention will be stopped, and the maternal/fetal condition will be managed by cesarean section.

5. Follow up: Continuous electronic fetal heart rate monitoring Maternal: vital data, uterine contractions, cervical changes (PV/4hours). Time to active phase (cervical dilatation: 6cm) will be noted, and then follow-up monitoring till delivery.

6. End point: Reaching maximum dose of drugs with failure of induction of labor in which another decision should be taken. Also, at any point there's fetal or maternal distress (e.g. pathological FHR pattern, antepartum hemorrhage, etc.) the study intervention will be stopped, and the maternal/fetal condition will be managed accordingly.

7. Data collection and recording case record form: The data will be collected in a case report form (age, parity, gestational age, blood pressure, bishop score on admission, time till active phase, induction to delivery interval, any side effects if present, mode of delivery, birth weight, neonatal intensive care unit (NICU) admission, Apgar score, hospital stay, maternal intensive care unit (ICU) admission.

Statistical analysis:

The collected data will be revised, coded, tabulated and introduced to a personal computer (PC) using Statistical package for Social Science (SPSS 20.0.1 for windows; SPSS Inc, Chicago, 2001). Quantitative variables will be expressed as mean and standard deviation (SD), or median and interquartile range (IQR) according to type of data. Qualitative variables are expressed as frequencies and percentages. Student t test and Mann Whitney test will be used to compare a continuous variable between two study groups. Chi square test will be used to examine the relationship between categorical variables. A P-value< 0.05 will be considered statistically significant.

Ethical and Safety Consideration:

This study will be done after approval of the ethical committee ,faculty of Medicine, Ain Shams University. Informed consent will be taken from all participants before recruitment in the study, and after explaining the purpose and procedures of the study. The investigator will obtain the written, signed informed consent of each subject prior to performing any study specific procedures on the subject. All data will be collected confidentially. At any point there's fetal or maternal distress (e.g. pathological FHR pattern, antepartum hemorrhage, etc.) the study intervention will be stopped, and the maternal/fetal condition will be managed accordingly.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ain Shams Maternity 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:

• Gestational age (36-42 weeks).
• Prelabor rupture of membranes within the last 24hours
• Vertex presentation

Exclusion Criteria:

1. History of medical diseases (HTN, diabetes milletus, systemic lupus erythematosus, cardiac, etc.).
2. Antepartum hemorrhage
3. Chorioamnionitis / prelabor rupture of membranes >24hours
4. Multiple pregnancy.
5. Abnormal fetal heart rate pattern upon admission
6. Intrauterine growth restriction
7. Fetal malpresentation.
8. Previous uterine scar.
9. Estimated fetal weight more than 4kg.
10. Patients already in labor
11. Contraindication for prostaglandin/oxytocin use (allergy,..)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: misoprostol group; 25µg misoprostol oral tablet every 4 hours with maximum200 µg	Drug: Misoprostol; a synthetic prostaglandin E1 analogue; Other Names: vagiprost
Active Comparator: oxytocin group; oxytocin infusion according to ASUMH local protocol: Put 3IU oxytocin (3000mIU) +50ml of normal saline in syringe pump= (60mIU/ml). Commence at 1ml/hour (1mIU/min) for 1/2 hour.; If contractions inadequate +fetal monitor healthy 2 ml/hour for 1/2 hour.; If contractions inadequate +fetal monitor healthy 4 ml/hour for 1/2 hour.; If contractions inadequate +fetal monitor healthy 6 ml/hour for 1/2 hour.; If contractions inadequate +fetal monitor healthy increase by 2ml/hr. for max. 27ml/hour. At any point there's fetal or maternal distress (e.g. pathological FHR pattern, antepartum hemorrhage, etc.) the study intervention will be stopped, and the maternal/fetal condition will be managed by cesarean section.	Drug: Syntocinon; synthetic oxytocin; Other Names: oxytocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
vaginal delivery	rate of successful vaginal delivery	immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
induction to active phase time	Time interval from starting induction till active phase (6cm dilatation)	during the intervention
Induction to delivery time	Time interval from starting induction till delivery	during the intervention
Apgar score	This scoring system provides a standardized assessment for infants after delivery. The Apgar score comprises five components: 1) color, 2) heart rate, 3) reflexes, 4) muscle tone, and 5) respiration, each of which is given a score of 0, 1, or 2.	The score is reported at 1 minute and 5 minutes after birth for all infants
NICU admission	number of newborns admitted to the neonatal intensive care unit	within 24hours after birth
maternal side effects	number of participants with temperature >38 degree celsius	during labour and within 24hours after birth

Collaborators and Investigators

• Sponsor: Ain Shams Maternity Hospital
• Investigators: Study Director: Mohamed S Sweed, MD, Professor; Study Chair: Gasser A Elbishry, MD, Professor

Publications and helpful links

General Publications

• Alfirevic Z, Aflaifel N, Weeks A. Oral misoprostol for induction of labour. Cochrane Database Syst Rev. 2014 Jun 13;2014(6):CD001338. doi: 10.1002/14651858.CD001338.pub3.
• Zeteroglu S, Engin-Ustun Y, Ustun Y, Guvercinci M, Sahin G, Kamaci M. A prospective randomized study comparing misoprostol and oxytocin for premature rupture of membranes at term. J Matern Fetal Neonatal Med. 2006 May;19(5):283-7. doi: 10.1080/14767050600589807.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): January 15, 2022
• Study Completion (Actual): May 16, 2022

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: oxytocin; misoprostol
• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Rupture; Fetal Membranes, Premature Rupture; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Oxytocin; Misoprostol
• Other Study ID Numbers: FMASU MS 733/2020/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: planning to share the study protocol, and master-sheet.
• IPD Sharing Time Frame: After study completion and for 6months later
• IPD Sharing Access Criteria: However, the repository is not decided upon yet
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

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