Back to results

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

Primary Purpose

Chorioamnionitis, Brain Injury

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

N-acetylcysteine

Control

About this trial

This is an interventional treatment trial for Chorioamnionitis focused on measuring chorioamnionitis, maternal chorioamnionitis, neonatal white matter injury, N-acetylcysteine, NAC, anti-oxidant treatment

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

N-acetylcysteine

Control

Arm Description

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

Outcomes

Primary Outcome Measures

NAC Terminal Elimination Half-life

NAC Volume of Distribution

NAC Total Body Clearance

NAC Concentrations

Placental Transfer Ratio

Ratio of NAC concentration in cord to maternal venous blood

Maternal and Infant Mean Blood Pressure Change

Cerebral Blood Flow

Resistive index in middle cerebral artery (MCA)

Prothrombin Time

prothrombin clotting time

Secondary Outcome Measures

Magnetic Resonance Spectroscopy of Infants

ratio of myoInositol / NAA concentrations in basal ganglia

Cytokine Level IL-1Ra in Plasma

anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)

Full Information

NCT ID

NCT00724594

First Posted

July 28, 2008

Last Updated

March 17, 2021

Sponsor

Medical University of South Carolina

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT00724594

Brief Title

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

Official Title

Safety of N-acetylcysteine in Maternal Chorioamnionitis

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical University of South Carolina

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chorioamnionitis, Brain Injury

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

46 (Actual)

8. Arms, Groups, and Interventions

Arm Title

N-acetylcysteine

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

N-acetylcysteine

Other Intervention Name(s)

Acetadote, NAC

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Control

Other Intervention Name(s)

Saline

Intervention Description

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

Primary Outcome Measure Information:

Title

NAC Terminal Elimination Half-life

Time Frame

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

Title

NAC Volume of Distribution

Time Frame

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

Title

NAC Total Body Clearance

Time Frame

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

Title

NAC Concentrations

Time Frame

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

Title

Placental Transfer Ratio

Description

Ratio of NAC concentration in cord to maternal venous blood

Time Frame

At time of delivery

Title

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

Title

Cerebral Blood Flow

Description

Resistive index in middle cerebral artery (MCA)

Time Frame

after NAC infusion

Title

Prothrombin Time

Description

prothrombin clotting time

Time Frame

after N-acetylcystiene or saline infusion

Secondary Outcome Measure Information:

Title

Magnetic Resonance Spectroscopy of Infants

Description

ratio of myoInositol / NAA concentrations in basal ganglia

Time Frame

36 - 40 weeks gestational age

Title

Cytokine Level IL-1Ra in Plasma

Description

anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)

Time Frame

after N-acetylcysteine infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dorothea D. Jenkins, MD

Organizational Affiliation

Medical University of South Carolina

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Eugene Chang, MD

Organizational Affiliation

Medical University of South Carolina (Obstetric Principal Investigator)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25064164

Citation

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.

Results Reference

result

PubMed Identifier

26545726

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs