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

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.

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.

Study Overview

• Status: Completed
• Conditions: Azithromycin; Postpartum Endometritis; Meconium Stained
• Intervention / Treatment: Drug: Azithromycin capsule (Zithromax, Pfizer) (250 mg); Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 002
    • Cairo University
  • Giza, Egypt, 002
    • Cairo University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 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.
2. Singleton living gestation
3. Cephalic presentation
4. Adequate pelvis
5. An informed written consent for the proposed study.

Exclusion Criteria:

1. Primigravids
2. Women with previous cesarean section
3. Multifetal gestation
4. Intrauterine fetal death
5. Malpresentations
6. Prematurity (<37 weeks )
7. Abnormally invasive placenta during the current pregnancy
8. Medical disorders with pregnancy
9. Contracted pelvis
10. Evidence of maternal infection
11. Allergy to azithromycin or other macrolides that is self-reported or documented in the medical record.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Azithromycin group; Azithromycin capsule (Zithromax, Pfizer) (250 mg / 12 hrs on empty stomach for 3 days).	Drug: Azithromycin capsule (Zithromax, Pfizer) (250 mg); 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.
Placebo Comparator: Placebo group; 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; A treatment that has no active properties

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Chair: Gamal GamalEldin Youssef, PHD, Cairo University; Study Director: Eman Aly Hussein Aly, PHD, Cairo University; Study Director: Ahmed Samir Rashwan, PHD, Cairo University

Publications and helpful links

Helpful Links

• Premature Rupture of Membranes: Overview, Premature Rupture of Membranes (at Term), Premature Preterm Rupture of Membranes. Medscape.
• Antibiotics for women with prelabour rupture of membranes at term, undergoing induction of labour after 12 hours - A randomized controlled trial. Sri Lanka Journal of Obstetrics and Gynaecology, 42(1), 12-20.
• Management of meconium-stained newborns in the delivery room.
• Postpartum endometritis
• What Is The Real Risk Of Infection After Waters Break?
• Azithromycin
• A Retrospective Study on the Risk of Respiratory Distress Syndrome in Singleton Pregnancies with Preterm Premature Rupture of Membranes between 24+0 and 36+6 Weeks, Using Regression Analysis for Various Factors
• • American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics (2016). Practice Bulletin No. 172: Premature Rupture of Membranes.
• Antibiotics for meconium-stained amniotic fluid in labour for preventing maternal and neonatal infections

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): October 4, 2021

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 12, 2021

Study Record Updates

• Last Update Posted (Actual): November 12, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Azithromycin; Placebo; Postpartum Endometritis
• Additional Relevant MeSH Terms: Uterine Diseases; Adnexal Diseases; Pelvic Inflammatory Disease; Endometritis; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: Azithromycin in MSAF cases

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No