ChorioamnionitisPhase 1/2NCT00724594

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

A Phase 1/2 study testing N-acetylcysteine in people with Chorioamnionitis and Brain Injury, run by Medical University of South Carolina at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 13 years and older
Conditions the study is for: Chorioamnionitis, Brain Injury
What is being tested?: N-acetylcysteine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: 1 siteUnited States
Study dates: Aug 2008to Aug 2014
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Medical University of South Carolina
Charleston, South Carolina, 29425

Other trials in United States

About this study

Official title: Safety of N-acetylcysteine in Maternal Chorioamnionitis

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.

Read the 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.

Conditions: Chorioamnionitis, Brain Injury
Being tested: N-acetylcysteine, Control
Keywords: chorioamnionitis, maternal chorioamnionitis, neonatal white matter injury, N-acetylcysteine, NAC, anti-oxidant treatment
Medical subject headings: Chorioamnionitis, Brain Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-acetylcysteineDrug
Also called Acetadote, NAC
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.
ControlDrug
Also called Saline
Saline was given in the same volume, at the same timing as NAC infusions

Study groups in NCT00724594
Study group	Role	What they receive
N-acetylcysteine	Experimental	Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts. Receives: Drug: N-acetylcysteine
Control	Active comparator	Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts. Receives: Drug: Control

What is being measured

The primary outcome is the main question the study is designed to answer.

NAC Terminal Elimination Half-life
Measured: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Volume of Distribution
Measured: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Total Body Clearance
Measured: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Concentrations
Measured: Peak: 30 minutes after NAC infusion. Cord: at delivery
Placental Transfer Ratio
Ratio of NAC concentration in cord to maternal venous blood
Measured: At time of delivery
Maternal and Infant Mean Blood Pressure Change
Measured: 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)
Measured: after NAC infusion
Prothrombin Time
prothrombin clotting time
Measured: after N-acetylcystiene or saline infusion

Secondary outcomes (2)

Magnetic Resonance Spectroscopy of Infants
ratio of myoInositol / NAA concentrations in basal ganglia
Measured: 36 - 40 weeks gestational age
Cytokine Level IL-1Ra in Plasma
anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)
Measured: after N-acetylcysteine infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2008Aug 2014

First posted29 Jul 2008 (estimated)
Study startAug 2008
Primary completionJul 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for ChorioamnionitisStudies of the same condition, open and under way.
More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Participant
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00724594
Sponsor's protocol ID: R01NS052448
Other IDs: R01NS052448
Status last verified: Mar 2021
First submitted: 28 Jul 2008
Last updated: 12 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 25064164
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.
PubMed 26545726

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Amnioinfusion for Chorioamnionitis: Targeting Neonatal Brain Injury Biomarkers
Chorioamnionitis Affecting Fetus or Newborn, Amnioinfusion
Recruiting
Comparing Infectious Morbidity Among Women With Meconium-stained Amniotic Fluid at Term, Between Those Treated With Prophylactic Antibiotics Zinacef vs. Placebo
Meconium-stained Amniotic Fluid, Chorioamnionitis
Active, not recruitingObservational study
IL-6 and Lactates in Cord Blood and Neonatal Outcomes
Fetal Infection, Fetal Inflammatory Response Syndrome
Enrolling by invitation
Planned Early Induction of Labor vs Expectant Management for PROM
Premature Rupture of Membranes (PROM)
Active, not recruitingObservational study
Association Between Neuraxial Labor Analgesia and Maternal and Neonatal Infectious Outcomes
Intrapartum Maternal Fever, Clinical Chorioamnionitis

All Chorioamnionitis trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety of N-acetylcysteine in Maternal Chorioamnionitis
ClinicalTrials.gov ID: NCT00724594
Acronym / sponsor ID: R01NS052448
Conditions: Chorioamnionitis, Brain Injury
Keywords: chorioamnionitis, maternal chorioamnionitis, neonatal white matter injury, N-acetylcysteine, NAC, anti-oxidant treatment
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Medical University of South CarolinaUniversity, hospital or other
Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
Study start: Aug 2008
Primary completion: Jul 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 29 Jul 2008 (estimated)
Results: Posted 30 Apr 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
N-acetylcysteine	Experimental	Drug: N-acetylcysteineMother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
Control	Active comparator	Drug: ControlMother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.

Who may qualify

Ages: 13 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
N-acetylcysteineAlso: Acetadote, NACNAC (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.	Drug	N-acetylcysteine
ControlAlso: SalineSaline was given in the same volume, at the same timing as NAC infusions	Drug	Control

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: after NAC infusion
Resistive index in middle cerebral artery (MCA)
Prothrombin Time
Time frame: after N-acetylcystiene or saline infusion
prothrombin clotting time

2 secondary outcomes

Magnetic Resonance Spectroscopy of Infants
Time frame: 36 - 40 weeks gestational age
Cytokine Level IL-1Ra in Plasma
Time frame: after N-acetylcysteine infusion

Results and safety

Results posted to the registry on 30 Apr 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NAC Infant	12	12
Control Infant	12	12
NAC Maternal	11	11
Control Maternal	11	10

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. Mean (Standard Deviation). Unit: hours

Measure	NAC Maternal n = 11	NAC Preterm Infants n = 7	NAC Term Infants n = 5
Value	1.2 (0.2)	7.5 (2.0)	5.1 (1.3)

Primary outcome: NAC Volume of Distribution

Time frame: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion. Mean (Standard Deviation). Unit: L/kg

Measure	NAC Maternal n = 11	NAC Preterm Infants n = 7	NAC Term Infants n = 5
Value	0.41 (0.07)	0.47 (0.04)	0.38 (0.09)

Primary outcome: NAC Total Body Clearance

Time frame: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion. Mean (Standard Deviation). Unit: mL/h/kg

Measure	NAC Maternal n = 11	NAC Preterm Infants n = 7	NAC Term Infants n = 5
Value	255 (61)	45.0 (8.2)	53.7 (11.3)

Primary outcome: NAC Concentrations

Time frame: Peak: 30 minutes after NAC infusion. Cord: at delivery. Mean (Standard Deviation). Unit: micromol/L

Measure	NAC Maternal n = 11	NAC Preterm Infants n = 7	NAC Term Infants n = 5
Peak NAC concentration in plasma	1222 (415)	49.0 (14.9)	92.3 (69.2)
NAC cord concentration	NA (NA)	370.7 (199.2)	639.7 (409.4)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Mothers were monitored for Adverse Events for up to 2 days after treatment. Infants were assessed for Adverse Events until discharge, Serious Adverse Events up to 30 days post-treatment.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NAC Infant	4 of 12 (33.3%)	5 of 12 (41.7%)	Not reported
Control Infant	3 of 12 (25%)	3 of 12 (25%)	Not reported
NAC Maternal	0 of 11 (0%)	2 of 11 (18.2%)	Not reported
Control Maternal	0 of 11 (0%)	2 of 11 (18.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25064164Wiest 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.
Derived from this study: PubMed 26545726Jenkins 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.

Related trials for Chorioamnionitis

Recruiting
Amnioinfusion for Chorioamnionitis: Targeting Neonatal Brain Injury Biomarkers
Chorioamnionitis Affecting Fetus or Newborn, Amnioinfusion
Recruiting
Comparing Infectious Morbidity Among Women With Meconium-stained Amniotic Fluid at Term, Between Those Treated With Prophylactic Antibiotics Zinacef vs. Placebo
Meconium-stained Amniotic Fluid, Chorioamnionitis
Active, not recruitingObservational study
IL-6 and Lactates in Cord Blood and Neonatal Outcomes
Fetal Infection, Fetal Inflammatory Response Syndrome
Enrolling by invitation
Planned Early Induction of Labor vs Expectant Management for PROM
Premature Rupture of Membranes (PROM)
Active, not recruitingObservational study
Association Between Neuraxial Labor Analgesia and Maternal and Neonatal Infectious Outcomes
Intrapartum Maternal Fever, Clinical Chorioamnionitis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dorothea D. Jenkins, MD principal investigator

Medical University of South Carolina

Eugene Chang, MD principal investigator

Medical University of South Carolina (Obstetric Principal Investigator)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing N-acetylcysteine in people with Chorioamnionitis and Brain Injury, run by Medical University of South Carolina at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

NAC Terminal Elimination Half-life (time frame: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00724594, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2021.