Evaluation of Systemic Hypothermia Initiated After 6 Hours of Age in Infants ≥36 Weeks Gestation With Hypoxic-Ischemic Encephalopathy: A Bayesian Evaluation. A Protocol for the NICHD Neonatal Research Network
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 168
- 试验地点
- 44
- 主要终点
- Death or Moderate or Severe Disability
研究概览
简要总结
This study is a randomized, placebo-controlled, clinical trial to evaluate whether induced whole-body hypothermia initiated between 6-24 hours of age and continued for 96 hours in infants ≥ 36 weeks gestational age with hypoxic-ischemic encephalopathy will reduce the incidence of death or disability at 18-22 months of age. The study will enroll 168 infants with signs of hypoxic-ischemic encephalopathy at 16 NICHD Neonatal Research Network sites, and randomly assign them to either receive hypothermia or participate in a non-cooled control group.
详细描述
Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized by acute or subacute brain injury due to asphyxia. In most cases the underlying cause and timing of injury are unknown, but many cases are diagnosed at or shortly after birth.
According to the World Health Organization, more than 722,000 children died from birth asphyxia and birth trauma worldwide in 2004. An estimated 50-75 percent of infants with severe (stage 3) HIE will die, with 55 percent of these deaths occurring in the first month.
The incidence of long-term complications depends on the severity of HIE. Up to 80 percent of infants who survive stage 3 HIE develop significant long-term neurological disabilities - mental retardation, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are normal.
Because animal data suggests that brain injury from HIE evolves over several hours to days after the initial asphyxic insult, induced hypothermia holds promise as a neuroprotective therapy. Additional trials are needed to help define the most effective cooling strategies.
With this in mind, and knowing that many babies with HIE arrive at neonatal intensive care units several hours after birth, this study will evaluate the safety and efficacy of initiating hypothermia 6-24 hours after birth.
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
- None
入排标准
- 年龄范围
- 6 Hours 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants born at 36 0/7ths weeks gestational age or greater (by best obstetrical estimate)
- •Postnatal age between 6 and 24 hours following birth
- •Infants with a high probability of acute hemodynamic compromise, such as those with:
- •An acute perinatal event (abruptio placenta, cord prolapse, severe FHR abnormality)
- •An Apgar score ≤ 5 at 10 minutes
- •Continued need for ventilation initiated at birth for at least 10 minutes
- •Cord pH or first postnatal blood gas pH at ≤ 1 hour of ≤ 7.0
- •Base deficit on cord gas or first postnatal blood gas at ≤ 1 hour of ≥ 16 mEq/L
- •Infants matching the above criteria who also have an abnormal neurological exam showing the presence of moderate or severe encephalopathy
- •Infants whose parents/legal guardians have provided consent for enrollment.
- •NOTE: These inclusion criteria are identical to the NICHD Neonatal Research Network's 2005 Hypothermia study (see links below), except for the time of entry (6-24 hours vs. < 6 hours of age).
排除标准
- •Any infant with a core body temperature (axilla, rectal) less than 34.0°C for greater than 1 hour
- •Presence of a known anomaly or chromosomal aberration
- •Birth weight < 1,800 grams
- •Infant in extremis
- •Infants whose parents/legal guardians or attending physician refuse consent
结局指标
主要结局
Death or Moderate or Severe Disability
时间窗: Birth to 18-22 months corrected gestational age
Severe disability was defined by any of the following: a Bayley III cognitive score \< 70 or Gross Motor Functional (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate. Moderate disability was defined as a Bayley III cognitive score between 70-84 and either a GMF level of 2 or a seizure disorder or a hearing deficit.
次要结局
- Number of Infants With a DNR Order(Birth to 18-22 months corrected gestational age)
- Number of Deaths in the NICU and Following Discharge(Birth to 18-22 months corrected gestational age)
- Number of Infants With Mild, Moderate and Severe Disability(Birth to 18-22 months corrected gestational age)
- Number of Infants With Any Disability Based on Level of Encephalopathy at Randomization(Birth to 18-22 months corrected gestational age)
- Number of Infants With Non-CNS Organ System Dysfunction(Birth to 18-22 months corrected gestational age)
- Number of Infants With a DNR Order and Support is Withdrawn(Birth to 18-22 months corrected gestational age)
- Number of Infants With Neonatal Seizures, With and Without EEG Abnormalities(Birth to 18-22 months corrected gestational age)
- Number of Infants With Moderate and Severe Disability(Birth to 18-22 months corrected gestational age)
- Number of Infants With a DNR Order That Died(Birth to 18-22 months corrected gestational age)