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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Safety of N-acetylcysteine in Maternal Chorioamnionitis

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: Medical University of South Carolina

Current Primary Outcome:

  • NAC Terminal Elimination Half-life [ Time Frame: 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 ]
  • NAC Total Body Clearance [ Time Frame: 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 ]
  • Placental Transfer Ratio [ Time Frame: At time of delivery ]
    Ratio of NAC concentration in cord to maternal venous blood
  • 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 ]
  • Cerebral Blood Flow [ Time Frame: prior to delivery and in newborn after delivery, during 2 days of NAC infusion ]
  • PT [ Time Frame: prior to delivery and in newborn DOL1 ]


Original Primary Outcome: mean blood pressure, cerebral perfusion, PT, histaminergic reactions [ Time Frame: prior to delivery and in newborn after delivery, during 2 days of NAC infusion ]

Current Secondary Outcome:

  • Magnetic Resonance Spectroscopy of Infants [ Time Frame: 36 - 40 weeks gestational age ]
  • Cytokine Levels in Plasma and CSF [ Time Frame: During 2 days of NAC infusion ]


Original Secondary Outcome: Pharmacokinetics of placental transport and CSF penetration- efficacy outcomes: NAA/choline ratio in MRS at 36 weeks gestation, cytokine levels in plasma and CSF, as related to NAC concentrations [ Time Frame: prior to delivery and in newborn after delivery, during 2 days of NAC infusion, and when infants reach at least 36 weeks gestation for MR imaging ]

Information By: Medical University of South Carolina

Dates:
Date Received: July 28, 2008
Date Started: August 2008
Date Completion:
Last Updated: May 8, 2015
Last Verified: May 2015