The TIME STUDY: A Randomized Controlled Trial of Therapeutic Hypothermia for Infants With Mild Encephalopathy in California
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 68
- 试验地点
- 5
- 主要终点
- Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)
研究概览
简要总结
The TIME study is a randomized, controlled trial to evaluate impact on early measures of neurodevelopment and the safety profile of therapeutic hypothermia in term neonates with Mild Hypoxic-Ischemic Encephalopathy who are < 6 hours of age. Neurodevelopmental outcome will be assessed at 12-14 months of age. The study will enroll 68 neonates randomized to therapeutic hypothermia or normothermia across 5 centers in California.
详细描述
The TIME study is a multi-center randomized, controlled trial of Therapeutic Hypothermia (TH) (33.5°C ± 0.5° for 72 hours) versus normothermia using targeted temperature management, initiated within 6 hours after birth in term neonates with Mild Hypoxic-Ischemic Encephalopathy (HIE). Mild encephalopathy will be identified using the 6 component modified Sarnat exam as in the Neonatal Research Network of the National Institute of Child Health and Human Development trials of TH for moderate-severe encephalopathy and will be expanded to include features of mild encephalopathy. Eligible subjects must demonstrate ≥ 2 exam abnormalities (mild, moderate, severe) but without evidence of moderate-severe encephalopathy (≥ 3 moderate or severe features). The primary outcome is neurodevelopmental outcome at 12-14 months of age. Secondary outcomes include evaluating the safety profile of therapeutic hypothermia in patients with Mild HIE. Therapeutic hypothermia is well tolerated and did not demonstrate serious safety concerns when evaluated in multiple large studies of neonates with moderate-severe HIE. It is now being applied by some practitioners to neonates with Mild HIE without systematic evidence of benefit or potential harm. This data will be necessary in order to develop and larger trial of efficacy to be determined at 2 years of age.
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 (Outcomes Assessor)
盲法说明
Assessors of neurodevelopmental outcome at 12-14 months of age will be blinded to the allotted treatment group
入排标准
- 年龄范围
- — 至 6 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(must meet all 3):
- •Neonates born at ≥ 36 0/7 weeks
- •Neonatal signs or contributing factors consistent with an acute peri-partum or intra-partum event (must meet a or b):
- •pH ≤ 7.0 or Base deficit ≥ 16 in any umbilical cord or baby specimen at ≤ 1 hr of age OR
- •No umbilical cord or baby blood gas at ≤ 1 hr of age OR pH 7.01-7.15 or Base deficit 10-15.9 in any cord or baby specimen at ≤ 1 hr of age AND at least one of the following
- •Apgar score at 10 min ≤ 5
- •Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, intubation with positive pressure ventilation)
- •Acute Perinatal Event: uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord), maternal trauma, maternal hemorrhage or cardiorespiratory arrest, fetal exsanguination from either vasa previa or feto-maternal hemorrhage
- •Fetal heart rate monitor pattern consistent with acute peripartum or intrapartum event (category III trace: no heart rate variability, presence of recurrent late or variable decelerations, bradycardia, or sinusoidal pattern)
- •Evidence of Mild Encephalopathy on Modified Sarnat Exam.
- •Presence of at least 2 signs of mild, moderate or severe encephalopathy with no more than 2 moderate or severe findings in the 6 tested categories (level of consciousness, spontaneous activity, posture, tone, neonatal reflexes (suck and moro), and autonomic nervous system
排除标准
- •Patients < 36 0/7 weeks birthweight < 1800gm; congenital or chromosomal anomaly associated with abnormal neurodevelopment or death; patients with moderate or severe HIE (by Sarnat exam or presence of clinical or electrographic seizures) identified within 6 hours after birth; core body temperature < 34°C for more than 1 hour prior to randomization.
研究组 & 干预措施
Therapeutic Hypothermia
Therapeutic hypothermia will be achieved using a servo-controlled temperature regulating blanket that is approved for use in neonates and is currently used for the treatment of neonates with moderate-severe HIE. The goal target temperature is 33.5°C ± 0.5°C for 72 hours and the subject will then be rewarmed at a rate of 0.5°C per hour to a goal of 36.5°C.
干预措施: Therapeutic Hypothermia (Other)
Normothermia
Normothermia will be achieved using a servo-controlled temperature regulating blanket with the temperature goal of 36.5-37.3°C for 72 hours.
干预措施: Normothermia (Other)
结局指标
主要结局
Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)
时间窗: Assessment takes up to 15 minutes and will be conducted at 12-14 months of age
Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be assessed at 12-14 months of age. The mean score for a 12 month old normally developing infant is 109 with a standard deviation of 16.5. Higher scores are associated with normal development.
Alberta Infant Motors Scale (AIMS)
时间窗: Assessment takes up to 15 minutes and will be conducted at 12-14 months of age
Alberta Infant Motors Scale (AIMS) will be assessed at 12-14 months of age. The AIMS score is determined by assessment of 4 positions and scoring the least and most mature position identified. The score is converted to a percentile for age with those in the 5th to 25th percentile identified as suspicious motor development and those with a score corresponding to \< 5th percentile being identified as abnormal motor development.
次要结局
- Percentage of participants with sinus bradycardia(72 hours)
- Percentage of participants thrombocytopenia(72 hours)
- Percentage of patients who require intubation and mechanical ventilation(72 hours)
- Percentage of participants diagnosed with seizures(During initial hospital stay up to 30 days)
- Age at initiation of feeds(During initial hospital stay up to 30 days from date of admission)
- Age at full enteral feeds(During initial hospital stay and up to 30 days from date of admission)
- Percentage of participants who require feeding assistance at discharge(At time of discharge from hospital, up to 30 days from admission)
- Percentage of participants exposed to inotropic agents(76 hours)
- Percentage of patients with need for central line(72 hours)
- Percentage of participants with Persistent Pulmonary Hypertension (PPHN)(72 hours)
- Percentage of participants exposed to sedating or analgesic medications(72 hours)
- Percentage of participants with fat necrosis and hypercalcemia(From study entry to day of hospital discharge, up to 30 days from admission)
- Percentage of participants discharged on anti-convulsant medications(At time of discharge from hospital, up to 30 days from admission)
- Count of participants with brain injury on MRI(At time of discharge from hospital, up to 30 days from admission)
- Length of Hospital Stay(At time of discharge from hospital, up to 30 days from admission)
- Percentage of participants breastfeeding at discharge(At time of discharge from hospital, up to 30 days from admission)
- Percentage of participants with death and/or hospice at discharge(At time of discharge from hospital, up to 30 days from admission)
研究者
Sonia Bonifacio
Clinical Associate Professor
Stanford University