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

Medical University of South Carolina (MUSC)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Chorioamnionitis

Brain Injury

Treatments

Drug: Control

Drug: N-acetylcysteine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00724594

R01NS052448 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

46 patients

Sex

All

Ages

13+ years old

Volunteers

No Healthy Volunteers

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