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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by Medical University of South Carolina.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00724594
First received: July 28, 2008
Last updated: September 10, 2009
Last verified: September 2009
  Purpose

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


Condition Intervention Phase
Chorioamnionitis
Brain Injury
Drug: N-acetylcysteine
Drug: Saline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Safety of N-acetylcysteine in Maternal Chorioamnionitis

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • mean blood pressure, cerebral perfusion, PT, histaminergic reactions [ Time Frame: prior to delivery and in newborn after delivery, during 2 days of NAC infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2008
Estimated Study Completion Date: July 2010
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NACL (low dose NAC)
Mothers will be given 100 mg/kg NAC as a loading dose within 4 hours of diagnosis of chorioamnionitis. Preterm infants will be given 12.5 mg/kg/dose, and near term infants will be given 25 mg/kg/dose very 12 hours for 5 doses.
Drug: N-acetylcysteine
Two different doses of NAC or saline will be given intravenously to mothers prior to delivery and thereafter to their newborns. Mother /infant pairs will be stratified by gestational age, into premature (P) and near-term (NT) gestational ages since the researchers expect different pharmacokinetics in the neonates. Each cohort will get the NAC doses, but the exact dose will be different between cohorts, to get the same serum concentration with different drug clearance in the premature (P) and near-term (NT) neonates. Control groups will receive only saline.
Other Name: Acetadote, NAC
Experimental: NACH (high dose NAC)
Mothers will be given 150 mg/kg NAC as a loading dose within 4 hours of diagnosis of chorioamnionitis. Preterm infants will be given 25 mg/kg/dose, and near term infants will be given 37.5 mg/kg/dose very 12 hours for 5 doses.
Drug: N-acetylcysteine
Two different doses of NAC or saline will be given intravenously to mothers prior to delivery and thereafter to their newborns. Mother /infant pairs will be stratified by gestational age, into premature (P) and near-term (NT) gestational ages since the researchers expect different pharmacokinetics in the neonates. Each cohort will get the NAC doses, but the exact dose will be different between cohorts, to get the same serum concentration with different drug clearance in the premature (P) and near-term (NT) neonates. Control groups will receive only saline.
Other Name: Acetadote, NAC
Active Comparator: C (control)
Saline will be given in the same volume as the NAC infusion.
Drug: Saline
Two different doses of NAC or saline will be given intravenously to mothers prior to delivery and their newborns after delivery. Control groups will receive only saline.

Detailed Description:

Chorioamnionitits is an intrauterine infection—an infection in the fluid and membranes surrounding the baby in utero. The infection, and the baby's response to the infection, can cause inflammation in the baby's brain which affects development. 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). Brain injury, particularly CP, has been shown to be 4-9 times higher in babies exposed to intrauterine infection than in normal infants. Treating both the mother and baby with antibiotics is part of routine care, however this has not been shown to change the risk for brain injury in the baby.

N-acetylcysteine (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. There are extensive clinical experience and safety data in pregnant mothers and preterm infants, established from acetaminophen overdose and European studies of NAC for prevention of chronic lung disease of prematurity.

In this pilot clinical trial, scientists will determine the safety of two different doses of NAC given to pregnant women who present with chorioamnionitis at greater than 24 weeks gestation.

In the trial, intravenous NAC will be given to mothers antenatally (and to their infants postnatally) who present with the diagnosis of chorioamnionitis, to evaluate safety and pharmacokinetics (PK) in mothers and infants. Mothers at 24 weeks gestation or greater and their infants will be randomized to receive either saline or one of two different doses of NAC within 4 hours of a clinical diagnosis of chorioamnionitis. NAC will be given to the mothers every 6 hours until delivery and every 12 hours to the infants after delivery for 2 days.

Information gained from this trial will be used to determine the best dose of NAC and to help estimate effect and sample sizes for a subsequent large clinical trial.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants must have 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 must have none of the following:

  • Asthma
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00724594

Contacts
Contact: Deanna Fanning, RN 843-792-7021 fanningd@musc.edu
Contact: Laura Grace Rollins 843-792-7965 lgrollins@gmail.com

Locations
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Deanna Fanning, RN    843-792-7021    fanningd@musc.edu   
Principal Investigator: Dorothea D. Jenkins, MD         
Principal Investigator: Eugene Chang, MD         
Sub-Investigator: Denise Mulvihill, MD         
Sub-Investigator: Don West, PharmD         
Sub-Investigator: Sandra Garner, PharmD         
Sub-Investigator: Toby Cox, PharmD         
Sub-Investigator: Anthony Hlavachek, MD         
Sub-Investigator: Renee Martin, PhD         
Sub-Investigator: John Schwacke, PhD         
Sponsors and Collaborators
Medical University of South Carolina
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)
  More Information

Publications:

Responsible Party: Dorothea D Jenkins MD, Principal Investigator, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00724594     History of Changes
Other Study ID Numbers: R01NS052448
Study First Received: July 28, 2008
Last Updated: September 10, 2009
Health Authority: United States: Federal Government

Keywords provided by Medical University of South Carolina:
chorioamnionitis
maternal chorioamnionitis
neonatal white matter injury
N-acetylcysteine
NAC
anti-oxidant treatment

Additional relevant MeSH terms:
Chorioamnionitis
Brain Injuries
Wounds and Injuries
Fetal Diseases
Pregnancy Complications
Fetal Membranes, Premature Rupture
Obstetric Labor Complications
Placenta Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on July 20, 2014