Safety of N-acetylcysteine in Maternal Chorioamnionitis (NAC in Chorio)
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| ClinicalTrials.gov Identifier: NCT00724594 |
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Recruitment Status :
Completed
First Posted : July 29, 2008
Results First Posted : April 30, 2015
Last Update Posted : April 12, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chorioamnionitis Brain Injury | Drug: N-acetylcysteine Drug: Control | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 46 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Participant) |
| Primary Purpose: | Treatment |
| Official Title: | Safety of N-acetylcysteine in Maternal Chorioamnionitis |
| Study Start Date : | August 2008 |
| Actual Primary Completion Date : | July 2014 |
| Actual Study Completion Date : | August 2014 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: N-acetylcysteine
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
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Drug: N-acetylcysteine
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.
Other Name: Acetadote, NAC |
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Active Comparator: Control
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
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Drug: Control
Saline was given in the same volume, at the same timing as NAC infusions
Other Name: Saline |
- 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
- Magnetic Resonance Spectroscopy of Infants [ Time Frame: 36 - 40 weeks gestational age ]ratio of myoInositol / NAA concentrations in basal ganglia
- Cytokine Level IL-1Ra in Plasma [ Time Frame: after N-acetylcysteine infusion ]anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)
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| Ages Eligible for Study: | 13 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00724594
| United States, South Carolina | |
| Medical University of South Carolina | |
| Charleston, South Carolina, United States, 29425 | |
| Principal Investigator: | Dorothea D. Jenkins, MD | Medical University of South Carolina | |
| Principal Investigator: | Eugene Chang, MD | Medical University of South Carolina (Obstetric Principal Investigator) |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Dorothea D. Jenkins, Associate Professor, Medical University of South Carolina |
| ClinicalTrials.gov Identifier: | NCT00724594 |
| Other Study ID Numbers: |
R01NS052448 ( U.S. NIH Grant/Contract ) R01NS052448 ( U.S. NIH Grant/Contract ) |
| First Posted: | July 29, 2008 Key Record Dates |
| Results First Posted: | April 30, 2015 |
| Last Update Posted: | April 12, 2021 |
| Last Verified: | March 2021 |
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chorioamnionitis maternal chorioamnionitis neonatal white matter injury |
N-acetylcysteine NAC anti-oxidant treatment |
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Brain Injuries Chorioamnionitis Brain Diseases Central Nervous System Diseases Nervous System Diseases Craniocerebral Trauma Trauma, Nervous System Wounds and Injuries Fetal Diseases Pregnancy Complications Fetal Membranes, Premature Rupture Obstetric Labor Complications Placenta Diseases |
Acetylcysteine N-monoacetylcystine Antiviral Agents Anti-Infective Agents Expectorants Respiratory System Agents Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Antidotes |