Safety of N-acetylcysteine in Maternal Chorioamnionitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- NAC Volume of Distribution
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
N-acetylcysteine
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
干预措施: N-acetylcysteine (Drug)
Control
Mother/infant pairs were stratified by gestational age into premature (P) and term (T) cohorts.
干预措施: Control (Drug)
结局指标
主要结局
NAC Volume of Distribution
时间窗: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Terminal Elimination Half-life
时间窗: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Total Body Clearance
时间窗: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
NAC Concentrations
时间窗: Peak: 30 minutes after NAC infusion. Cord: at delivery
Placental Transfer Ratio
时间窗: At time of delivery
Ratio of NAC concentration in cord to maternal venous blood
Maternal and Infant Mean Blood Pressure Change
时间窗: Maternal mean BP changes were pre/post dosing prior to delivery. Infant measurements were pre/post their first dosing
Cerebral Blood Flow
时间窗: after NAC infusion
Resistive index in middle cerebral artery (MCA)
Prothrombin Time
时间窗: after N-acetylcystiene or saline infusion
prothrombin clotting time
次要结局
- Cytokine Level IL-1Ra in Plasma(after N-acetylcysteine infusion)
- Magnetic Resonance Spectroscopy of Infants(36 - 40 weeks gestational age)
研究者
Dorothea D. Jenkins
Associate Professor
Medical University of South Carolina