Safety of N-acetylcysteine in Maternal Chorioamnionitis (NAC in Chorio)

March 17, 2021 updated by: Dorothea D. Jenkins, Medical University of South Carolina

Safety of N-acetylcysteine in Maternal Chorioamnionitis

The purpose of this trial was to find the best dose of N-acetylcysteine (NAC) to decrease brain injury in babies exposed to intrauterine infection without causing significant side effects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chorioamnionitits is an infection in the fluid and membranes surrounding the baby in utero. Intrauterine infection is associated with significant white and grey matter brain injury in newborns and is particularly important in the pathogenesis of periventricular leukomalacia (PVL) and cerebral palsy (CP). CP has been shown to be 4-9 times higher in babies exposed to intrauterine infection than in normal infants. Antibiotics have not changed the risk for brain injury in the newborn.

NAC is a promising anti-oxidant therapy that has shown effective neuroprotection in an animal model of chorioamnionitis, and has a favorable safety profile with limited and manageable side effects.

In this trial, intravenous NAC was given to mothers antenatally and to their infants postnatally, who presented with the diagnosis of chorioamnionitis, to evaluate safety and pharmacokinetics (PK) in mothers and infants. Mothers at ≥24 weeks gestation and their infants were randomized to receive either saline NAC within 4 hours of a clinical diagnosis of chorioamnionitis. Infants were stratified into term (≥ 33wk) and preterm (24-32wk) cohorts, due to different expected rates of metabolism and clearance.

Information gained from this trial will be used to determine how rapidly NAC is metabolized by mother, fetus, infant, and the ability of NAC to cross placenta. This study will also elucidate the safety of NAC in the setting of chorioamnionitis for fetal neuroprotection.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

9 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Participants had all of the following to qualify:

  • Chorioamnionitis, defined as either 1) clinical diagnosis of choriomanionitis 2) maternal fever greater than or equal to 100 degrees F in the presence of rupture of membranes or 2 of the following: uterine tenderness, maternal WBC > 15,000 cells/mm, fetal tachycardia > 160 bpm, malodorous amniotic fluid, or in preterm group only, rupture of membranes and active preterm labor.
  • Gestational age ≥ 24 completed weeks, by first trimester ultrasound or date of last menstrual period.
  • No greater than 4 hours from onset of fever or diagnosis.

Exclusion Criteria:

Participants had none of the following:

  • Asthma, steroid-dependent
  • Clinical sepsis, whether viral or bacterial in nature, defined as fever with signs of cardiovascular compromise in mother (blood pressure < 90/50, heart rate > 120 bpm, need for oxygen due to maternal saturations below 92%, pneumonia, pyelonephritis, or meningitis)
  • Seizure disorder
  • Fetal weight or biparietal diameter less than the 10th% for gestational age
  • Suspected major genetic or congenital abnormality
  • Fetal distress which demands immediate delivery (poor fetal biophysical profile, late decelerations, sinusoidal fetal heart rate pattern)
  • Participation in another therapeutic clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: N-acetylcysteine
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
Drug: N-acetylcysteine
NAC (100 mg/kg/dose) was given intravenously to mothers within 4 hours of diagnosis of chorioamnionitis, and every 6 hours until delivery. NAC was given to preterm (12.5 mg/kg/dose) and term infants (25 mg/kg/dose) every 12 hours for 5 doses after birth.
Other Names:
  • Acetadote, NAC
Active Comparator: Control
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
Drug: Control
Saline was given in the same volume, at the same timing as NAC infusions
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NAC Terminal Elimination Half-life
Time Frame: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Volume of Distribution
Time Frame: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Total Body Clearance
Time Frame: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Concentrations
Time Frame: Peak: 30 minutes after NAC infusion. Cord: at delivery
Peak: 30 minutes after NAC infusion. Cord: at delivery
Placental Transfer Ratio
Time Frame: At time of delivery
Ratio of NAC concentration in cord to maternal venous blood
At time of delivery
Maternal and Infant Mean Blood Pressure Change
Time Frame: Maternal mean BP changes were pre/post dosing prior to delivery. Infant measurements were pre/post their first dosing
Maternal mean BP changes were pre/post dosing prior to delivery. Infant measurements were pre/post their first dosing
Cerebral Blood Flow
Time Frame: after NAC infusion
Resistive index in middle cerebral artery (MCA)
after NAC infusion
Prothrombin Time
Time Frame: after N-acetylcystiene or saline infusion
prothrombin clotting time
after N-acetylcystiene or saline infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Magnetic Resonance Spectroscopy of Infants
Time Frame: 36 - 40 weeks gestational age
ratio of myoInositol / NAA concentrations in basal ganglia
36 - 40 weeks gestational age
Cytokine Level IL-1Ra in Plasma
Time Frame: after N-acetylcysteine infusion
anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)
after N-acetylcysteine infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of South Carolina

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Dorothea D. Jenkins, MD, Medical University of South Carolina
  • Principal Investigator: Eugene Chang, MD, Medical University of South Carolina (Obstetric Principal Investigator)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

July 28, 2008

First Submitted That Met QC Criteria

July 28, 2008

First Posted (Estimate)

July 29, 2008

Study Record Updates

Last Update Posted (Actual)

April 12, 2021

Last Update Submitted That Met QC Criteria

March 17, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01NS052448 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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