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

NCT00724594 | Completed Phase 1 Results DMC

• 1 other identifier: R01NS052448
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Chorioamnionitis; Brain Injury

Keywords

chorioamnionitis; maternal chorioamnionitis; neonatal white matter injury; N-acetylcysteine; NAC; anti-oxidant treatment

Outcome Measures

Primary Outcomes (8)

• NAC Terminal Elimination Half-life

  prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion

• NAC Volume of Distribution

  prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion

• NAC Total Body Clearance

  prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion

• NAC Concentrations

  Peak: 30 minutes after NAC infusion. Cord: at delivery

• Placental Transfer Ratio

  Ratio of NAC concentration in cord to maternal venous blood

  At time of delivery

• Maternal and Infant Mean Blood Pressure Change

  Maternal mean BP changes were pre/post dosing prior to delivery. Infant measurements were pre/post their first dosing

• Cerebral Blood Flow

  Resistive index in middle cerebral artery (MCA)

  after NAC infusion

• Prothrombin Time

  prothrombin clotting time

  after N-acetylcystiene or saline infusion

Secondary Outcomes (2)

• Magnetic Resonance Spectroscopy of Infants

  36 - 40 weeks gestational age

• Cytokine Level IL-1Ra in Plasma

  after N-acetylcysteine infusion

Study Arms (2)

N-acetylcysteine

EXPERIMENTAL

Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.

Drug: N-acetylcysteine

Control

ACTIVE COMPARATOR

Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.

Drug: Control

Interventions

N-acetylcysteine DRUG

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.

Also known as: Acetadote, NAC

N-acetylcysteine

Control DRUG

Saline was given in the same volume, at the same timing as NAC infusions

Also known as: Saline

Control

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (2)

• Wiest DB, Chang E, Fanning D, Garner S, Cox T, Jenkins DD. Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in chorioamnionitis for fetal neuroprotection. J Pediatr. 2014 Oct;165(4):672-7.e2. doi: 10.1016/j.jpeds.2014.06.044. Epub 2014 Jul 23.

  PMID: 25064164 RESULT

• Jenkins DD, Wiest DB, Mulvihill DM, Hlavacek AM, Majstoravich SJ, Brown TR, Taylor JJ, Buckley JR, Turner RP, Rollins LG, Bentzley JP, Hope KE, Barbour AB, Lowe DW, Martin RH, Chang EY. Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis. J Pediatr. 2016 Jan;168:67-76.e6. doi: 10.1016/j.jpeds.2015.09.076. Epub 2015 Nov 3.

  PMID: 26545726 DERIVED

MeSH Terms

Conditions

Chorioamnionitis; Brain Injuries

Interventions

Acetylcysteine; Sodium Chloride

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Membranes, Premature Rupture; Obstetric Labor Complications; Placenta Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Dorothea Jenkins
• Organization: Medical University of South Carolina

jenkd@musc.edu

843-792-4341

Study Officials

• Dorothea D. Jenkins, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Eugene Chang, MD

  Medical University of South Carolina (Obstetric Principal Investigator)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: July 29, 2008
• Study Start: August 1, 2008
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: April 12, 2021
• Results First Posted: April 30, 2015

Record last verified: 2021-03

Locations

US (1)