A Randomized Trial of Targeted Temperature Management With Whole Body Hypothermia For Moderate And Severe Hypoxic-Ischemic Encephalopathy In Premature Infants 33-35 Weeks Gestational Age.
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
- 36
- 主要终点
- Death or Moderate or Severe Disability
研究概览
简要总结
This study is a randomized, controlled trial to assess safety and effectiveness of whole body hypothermia for 72 hours in preterm infants 33-35 weeks gestational age (GA) who present at <6 hours postnatal age with moderate to severe neonatal encephalopathy (NE). The study will enroll infants with signs of NE at 18 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
Most clinical studies of neonatal encephalopathy (NE) and potential interventions have focused on infants ≥36 weeks GA. Although many interventions have been suggested and assessed for prevention or palliation of NE, the only one currently supported by rigorous clinical evidence to improve outcome in human newborns has been hypothermia implemented at <6 hours of postnatal age and maintained for 72 hrs. Data about diagnosis, frequency, severity, and outcome of NE in infants 33-35 weeks GA are sparse.
This trial will assess safety and effectiveness of whole body hypothermia for 72 hours in preterm infants 33-35 weeks gestational age (GA) who present at <6 hrs postnatal age with moderate to severe neonatal encephalopathy. Infants 33 0/7 to 35 6/7 weeks GA (best obstetrical estimate) and greater than or equal to 1500 grams birth weight (selected to minimize potential difficulties placing esophageal probe) who meet clinical, biochemical and neurologic criteria for moderate to severe NE will be randomized to either whole body hypothermia or participate in a non-cooled control group. The primary outcome will be death or moderate to severe disability at 18-22 months corrected age. The presence or absence of disability will be determined by the standard NRN interdisciplinary follow-up exam.
Secondary Study includes determining an association between MRI detectable injury and neurodevelopment at 18-22 months.
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
- 33 Weeks 至 35 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants 33 0/7 to 35 6/7 weeks GA (best obstetrical estimate)
- •Infants weight greater than or equal to 1500 grams at birth
- •Postnatal age less than 6 hours
- •Infants who meet clinical, biochemical and neurologic criteria for moderate to severe NE:
- •Biochemical: Cord gas or blood gas within first hour of life with pH ≤7.00 or base deficit (BD) ≥16 mEq/L OR
- •Acute perinatal event (e.g., abruptio placenta, cord prolapse, uterine rupture, severe FHR abnormality such as variable or late decelerations) AND Requirement for positive pressure ventilation for apnea or poor respiratory effort since birth for at least 10 minutes OR 10 minute Apgar score ≤5
- •Neurologic:
- •Seizures OR modified Sarnat score with abnormalities in at least 3 of the 6 categories; at least one must be altered level of consciousness (lethargy or stupor/coma) as determined by a certified examiner (All infants who meet criteria for potential inclusion will undergo standard neurologic exam as for infants ≥36 wks GA being considered for hypothermia, with findings recorded)
排除标准
- •Receipt of sedative, analgesic or paralytic agent that may confound the qualifying neurologic exam
- •Etiology of NE not likely to be hypoxic-ischemic in origin
- •Major congenital anomaly that may confound outcome
- •Considered to be moribund and will not be receiving full intensive care
- •Equipment and/or appropriate staff not available
- •Core temperature < 33.5oC for more than one hour at time of screening
- •Unable to randomize by 6 hours of age
- •Infant needs ECMO
- •All blood gases (cord and postnatal at < 1hr of age) have a pH > 7.15 AND a base deficit < 10mEq/L
结局指标
主要结局
Death or Moderate or Severe Disability
时间窗: Birth to 18-22 months corrected age
Severe disability was defined by any of the following: a Bayley III cognitive score \< 70 or Gross Motor Function (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to following 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
- Causes of Death(Birth to 18-22 months corrrected age)
- Number of Infants With Moderate or Severe Disability(Birth to 18-22 months corrrected age)
- Number of Infants With Abnormal MRIs During Post-intervention Period(Post-intervention to through discharge, death, or transfer (whichever comes first), average of 29 days)
- Neurological Injury by Cranial Ultrasound During Intervention(Within 6 hours of life to 72 hours after start of intervention)
- Number of Deaths in the NICU and Following Discharge(Birth to 18-22 months corrected age)