Efficacy of Azithromycin in MSAF Cases to Improve Maternal and Neonatal Outcomes

Study Overview
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Brief Summary
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Meconium stained amniotic fluid increases the risk of maternal complications (e.g., dystocia, operative delivery, and postpartum endometritis) and neonatal complications (e.g., sepsis, admission to the neonatal intensive care unit [NICU], and meconium aspiration syndrome). The goal of the study is to compare between Azithromycin vs Placebo in cases of meconium stained amniotic fluid during the first stage of labor in multigravida women and their effect on maternal and neonatal outcomes.

Detailed Description
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Meconium stained amniotic fluid, a troublesome situation both for obstetrician and pediatrician, it is associated with high rates of caesarean section, perinatal morbidity and mortality. The rate of meconium-stained amniotic fluid varies from 12 to 20%.It is higher in underdeveloped countries.Our study design would be a prospective randomized trial. Consented, eligible pregnant women presenting during the first stage of labor at or more than 37 weeks of gestation with meconium stained amniotic fluid will be randomized to receive Azithromycin capsule (Zithromax, Pfizer) (250 mg / 12hrs on empty stomach for 3 days)(Group 1).Group 2 will be offered placebo capsules (manufactured in pharmacy department with the same shape, color and consistency as Azithromycin capsule for 3 days).

Official Title
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Comparison Between Azithromycin vs Placebo in Cases of Meconium Stained Amniotic Fluid During the First Stage of Labor in Multigravida Women and Their Effect on Maternal and Neonatal Outcomes, a Double-blind, Placebo-controlled Randomized Clinical Trial.

Conditions
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Meconium Stained, Azithromycin, Postpartum Endometritis

Intervention / Treatment
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* Drug: Azithromycin capsule (Zithromax, Pfizer) (250 mg)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multigravida pregnant women with meconium stained amniotic fluid encountered either by spontaneous/artificial amniotomy during the first stage of labor in the ward provided that the gestational age at delivery is 37 weeks of gestation or more. Singleton living gestation Cephalic presentation Adequate pelvis An informed written consent for the proposed study. Exclusion Criteria: Primigravids Women with previous cesarean section Multifetal gestation Intrauterine fetal death Malpresentations Prematurity (<37 weeks ) Abnormally invasive placenta during the current pregnancy Medical disorders with pregnancy Contracted pelvis Evidence of maternal infection Allergy to azithromycin or other macrolides that is self-reported or documented in the medical record.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible participant will be allocated to one of two groups : Group 1 will be offered Azithromycin capsule (Zithromax, Pfizer) (250 mg / 12 hrs on empty stomach for 3 days). Group 2 will be offered placebo capsules (manufactured in pharmacy department with the same shape, colour and consistency as Azithromycin capsule for 3 days). A single pharmacist will be responsible for manufacturing of placebo capsules and packing all medications into sterile boxes and labelling of them as 1 or 2.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Azithromycin group<br>Azithromycin capsule (Zithromax, Pfizer) (250 mg / 12 hrs on empty stomach for 3 days). | Drug: Azithromycin capsule (Zithromax, Pfizer) (250 mg)<br>* Azithromycin, a second generation macrolide, broad-spectrum antibacterial that stops bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections Azithromycin has additional immunomodulatory effects and has been used in chronic respiratory inflammatory diseases for this purpose. .Azithromycin has been beneficial in the treatment of influenza and Middle East respiratory syndrome coronavirus (MERS-CoV) and recently has shown to be effective against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) when used in combination with hydroxychloroquine or chloroquine.<br>|
| Placebo Comparator: Placebo group<br>placebo capsules (manufactured in pharmacy department with the same shape, color and consistency as Azithromycin capsule every 12hrs for 3 days). A single pharmacist will be responsible for manufacturing of placebo capsules and packing all medications into sterile boxes and labelling of them as 1 or 2. | Drug: Placebo<br>* A treatment that has no active properties<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Azithromycin vs Placebo in cases of meconium stained amniotic fluid during the first stage of labor in multigravida women and their effect on occurrence of maternal fever, postpartum endometritis and skin (episiotomy/tear) infection. | Mothers will be followed up during her stay in the postnatal ward regarding signs of infection (fever, maternal tachycardia, offensive vaginal discharge, uterine tenderness). Postpartum follow up visit 1 week after delivery will be conducted. | within 1 week from delivery | 
| Azithromycin vs Placebo in cases of meconium stained amniotic fluid during the first stage of labor in multigravida women and their effect on occurrence of neonatal fever , pneumonia and skin infection . | Neonates were followed up for incidence of neonatal pneumonia, neonatal skin infection , neonatal fever. | within 1 week from delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal necessity for NICU admission and/or mechanical ventilation. | Incidence of NICU admission and/or mechanical ventilation in neonates born to women with MSAF | after delivery and within 1 week postartum | 
| Occurrence of meconium aspiration | Neonates will be followed up for presence or absence of meconium aspiration, APGAR score at 1 and 5 minutes, RDS. | after delivery and within 1 week postpartum | 
| 2- Side effects of drug (diarrhea, stomach cramps, vomiting, allergy and anaphylactic shock). | Mothers follow up for incidence of side effects related to Azithromycin | wwithin 1 week postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postpartum Endometritis, Azithromycin, Placebo