A Phase 1/2 interventional study of N-acetylcysteine and Control in Chorioamnionitis and Brain Injury, sponsored by Medical University of South Carolina. Completed at 1 site in United States. Open to participants aged 13 Years and older. Per ClinicalTrials.gov, last updated 2021-04-12.
Sponsored by Medical University of South Carolina · Phase 1/2, Interventional, and Treatment
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.
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.
39 studies on the registry are indexed under Chorioamnionitis; 9 are open to participants now.
This study's enrollment of 46 is below the median of 157 across 22 interventional studies indexed under Chorioamnionitis.
Browse Chorioamnionitis studies →Medical University of South Carolina is the lead sponsor of 874 studies on the registry; 166 are open to participants now.
Of its 131 completed or terminated interventional studies of FDA-regulated products, 104 (79%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participants had all of the following to qualify:
Exclusion Criteria:
Participants had none of the following:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
Drug: N-acetylcysteine
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
Drug: Control
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
Saline was given in the same volume, at the same timing as NAC infusions
Also known as: 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
Ratio of NAC concentration in cord to maternal venous blood
Time frame: At time of delivery
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
Resistive index in middle cerebral artery (MCA)
Time frame: after NAC infusion
Prothrombin Time
prothrombin clotting time
Time frame: after N-acetylcystiene or saline infusion
Magnetic Resonance Spectroscopy of Infants
ratio of myoInositol / NAA concentrations in basal ganglia
Time frame: 36 - 40 weeks gestational age
Cytokine Level IL-1Ra in Plasma
anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)
Time frame: after N-acetylcysteine infusion
| Milestone | NAC Infant | Control Infant | NAC Maternal | Control Maternal |
|---|---|---|---|---|
| Started | 12 | 12 | 11 | 11 |
| Completed | 12 | 12 | 11 | 10 |
| Not completed | 0 | 0 | 0 | 1 |
| hours | NAC Maternal | NAC Preterm Infants | NAC Term Infants |
|---|---|---|---|
| NAC Terminal Elimination Half-life | 1.2 ± 0.2 | 7.5 ± 2.0 | 5.1 ± 1.3 |
| L/kg | NAC Maternal | NAC Preterm Infants | NAC Term Infants |
|---|---|---|---|
| NAC Volume of Distribution | 0.41 ± 0.07 | 0.47 ± 0.04 | 0.38 ± 0.09 |
| mL/h/kg | NAC Maternal | NAC Preterm Infants | NAC Term Infants |
|---|---|---|---|
| NAC Total Body Clearance | 255 ± 61 | 45.0 ± 8.2 | 53.7 ± 11.3 |
| micromol/L | NAC Maternal | NAC Preterm Infants | NAC Term Infants |
|---|---|---|---|
| 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 |
Ratio of NAC concentration in cord to maternal venous blood
| ratio | NAC Maternal |
|---|---|
| Placental Transfer Ratio | 1.4 ± 0.8 |
| mmHg | NAC Infants | Control Infants | NAC Maternal | Control Maternal |
|---|---|---|---|---|
| Maternal and Infant Mean Blood Pressure Change | -1.2 ± 13 | 2.1 ± 11 | 1 ± 12 | 2 ± 10 |
Resistive index in middle cerebral artery (MCA)
| units on a scale | NAC Term Infants | Control Term Infants | NAC Preterm Infants | Control Preterm Infants |
|---|---|---|---|---|
| Cerebral Blood Flow | 0.93 (0.87 to 0.99) | 0.89 (0.81 to 0.97) | 0.92 (0.88 to 0.97) | 0.89 (0.82 to 0.95) |
prothrombin clotting time
| seconds | NAC Infant | Control Infant | NAC Maternal | Control Maternal |
|---|---|---|---|---|
| Prothrombin Time | 19.5 ± 2.5 | 19.0 ± 4.0 | 14.2 ± 0.6 | 14.4 ± 1.2 |
ratio of myoInositol / NAA concentrations in basal ganglia
| ratio | NAC Infants | Control Infants |
|---|---|---|
| Magnetic Resonance Spectroscopy of Infants | 1.09 ± 0.31 | 1.34 ± 0.20 |
anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)
| pg/ml | NAC Infants | Control Infants |
|---|---|---|
| Cytokine Level IL-1Ra in Plasma | 745 (251 to 1302) | 8.3 (8.3 to 448) |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| NAC Infant | — | 4/12 (33.3%) | 5/12 (41.7%) |
| Control Infant | — | 3/12 (25%) | 3/12 (25%) |
| NAC Maternal | — | 0/11 (0%) | 2/11 (18.2%) |
| Control Maternal | — | 0/11 (0%) | 2/11 (18.2%) |
| Event | NAC Infant | Control Infant | NAC Maternal | Control Maternal |
|---|---|---|---|---|
| IVH 5-7 days of ageNervous system disorders | 2/12 | 0/12 | 0/11 | 0/11 |
| DeathGeneral disorders | 0/12 | 1/12 | 0/11 | 0/11 |
| IVH 1-2 days of ageNervous system disorders | 1/12 | 1/12 | 0/11 | 0/11 |
| NEC within 30 daysNervous system disorders | 1/12 | 1/12 | 0/11 | 0/11 |
| PneumoniaImmune system disorders | 1/12 | 0/12 | 0/11 | 0/11 |
| Hypoxic Ischemic EncephalopathyNervous system disorders | 1/12 | 0/12 | 0/11 | 0/11 |
| Culture Proven SepsisImmune system disorders | 1/12 | 1/12 | 0/11 | 0/11 |
| Event | NAC Infant | Control Infant | NAC Maternal | Control Maternal |
|---|---|---|---|---|
| Prolonged PT timeBlood and lymphatic system disorders | 5/8 | 3/6 | 0/11 | 0/11 |
| Rash/HivesSkin and subcutaneous tissue disorders | 0/12 | 0/12 | 1/11 | 0/11 |
| Shortness of breath/wheezingRespiratory, thoracic and mediastinal disorders | 0/12 | 0/12 | 0/11 | 1/11 |
| HypotensionBlood and lymphatic system disorders | 0/12 | 1/12 | 1/11 | 1/11 |
| Age, Customized(participants) | NAC Infant | Control Infant | NAC Maternal | Control Maternal | Total |
|---|---|---|---|---|---|
| Preterm Infants | 7 | 7 | NA | NA | NA |
| Term Infants | 5 | 5 | NA | NA | NA |
| Mothers aged 18-45years | NA | NA | 11 | 11 | NA |
| Sex: Female, Male(Participants) | NAC Infant | Control Infant | NAC Maternal | Control Maternal | Total |
|---|---|---|---|---|---|
| Female | 5 | 6 | 11 | 11 | 33 |
| Male | 7 | 6 | 0 | 0 | 13 |
| Race (NIH/OMB)(Participants) | NAC Infant | Control Infant | NAC Maternal | Control Maternal | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 9 | 5 | 8 | 4 | 26 |
| White | 3 | 7 | 3 | 7 | 20 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | NAC Infant | Control Infant | NAC Maternal | Control Maternal | Total |
|---|---|---|---|---|---|
| United States | 12 | 12 | 11 | 11 | 46 |
This study is completed, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Acetylcysteine
Medical University of South Carolina →