Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterm Infants
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 650
- 试验地点
- 32
- 主要终点
- Bayley III Composite Cognitive Score
研究概览
简要总结
Study Hypothesis: Preterm infants administered weekly Darbe during the neonatal period will have improved neurocognitive outcome at 22-26 months compared to placebo
详细描述
Advances in neonatal care have led to significant improvements in the survival of the nearly 60,000 very low birth weight (VLBW) infants born each year in the U.S. Improving neurodevelopmental outcomes for these preterm infants continues to be a major goal for neonatal care providers. A subset of these infants sustain a grade 3 or 4 intraventricular hemorrhage (IVH) resulting in an increase in the incidence of developmental delay. Moreover, almost one third of preterm infants with normal head ultrasounds also develop cognitive delay. Although a variety of neuroprotective treatment strategies have been evaluated, no specific treatment has been identified to reduce or prevent brain injury in these most vulnerable preterm infants.
A potential neuroprotective therapy involves administering erythropoiesis stimulating agents (ESAs) such as erythropoietin (Epo) and Darbepoetin (Darbe, a longer acting ESA). In addition to stimulating erythropoiesis, ESAs have been shown to be protective in the developing brain in animal models, making it possibly beneficial for very premature infants who are at risk for intraventricular hemorrhage, hypoxic-ischemic injury, and developmental delay. The neuroprotective mechanisms of ESAs include increased neurogenesis, decreased neuronal susceptibility to glutamate toxicity, decreased neuronal apoptosis, decreased inflammation, decreased nitric oxide-mediated injury, increased antioxidant response, decreased axonal degeneration, and increased protective effects on glia. This is a randomized, masked, placebo controlled clinical study in which enrolled infants will receive weekly Darbe or placebo (sham) dosing.
Extended follow-up: Subjects will be seen for follow-up at 4-5 years (i.e., 4 years - 4 years 11 months) corrected age and 6-7 years (i.e., 6 years - 6 years 11 months) corrected age to characterize the functional, behavioral and neurological outcomes of the extremely low birth weight (ELBW) population at school age based on treatment with darbepoetin versus placebo in the neonatal period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Primary providers and bedside caregivers will be blinded to randomization group. If the dose will be administered IV, the study drug will be administered slow IV push by the bedside nurse. If the dose will be administered subcutaneously, the study drug will be brought to the bedside in a closed container, and injections will be shielded behind screens and out of earshot from caregivers and parents. An adhesive bandage (or 2x2 gauze) will be placed over the true and sham injection sites and either taped or held in place until no evidence of the injection is visible. The parents, medical providers, data collection staff and neurodevelopmental follow up personnel will be masked to the treatment arm.
入排标准
- 年龄范围
- 1 Hour 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inborn and outborn preterm infants
- •23 0/7-28 6/7 weeks gestational age
- •≤24 hours postnatal age
排除标准
- •Hematocrit > 60%
- •Infants with known congenital or chromosomal anomalies, including congenital heart disease and known brain anomalies
- •Hemorrhagic or hemolytic disease
- •EEG- confirmed seizures
- •Congenital thrombotic disease
- •Systolic blood pressures >100 mm Hg while not on pressor support
- •Receiving Epo or Darbe clinically, or planning to receive Epo or Darbe during hospitalization
- •Infants in whom no aggressive therapy is planned
- •Family will NOT be available for follow-up at 22-26 months
研究组 & 干预措施
Darbepoetin
Darbepoetin 10 micrograms/kg/once every week (IV or SC)
干预措施: Darbepoetin (Drug)
Placebo
Equal volume normal saline for IV administration, or sham dosing
干预措施: Placebo (Drug)
结局指标
主要结局
Bayley III Composite Cognitive Score
时间窗: 22-26 months corrected age (a median of 25 months corrected age, which corresponds to a median of 29 months calendar age in the analysis population), unless the subject died earlier
Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score, where subjects who died prior to the follow-up assessment are assigned the lowest possible score of 54. This is a standardized scale where a score that is more than 1 normative standard deviation from the normative mean of 100 signifies mild developmental delay (score \< 85); 2 standard deviations below the mean, moderate delay (score \< 70); and 3 standard deviations below the mean, severe delay (score \< 55). This self-standing scale comprises the primary outcome for the Darbe study.
次要结局
- Number of Transfusions Per Infant(Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks))
- Total Volume of Transfusions Per Infant(Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks))
- Number of Donor Exposures Per Infant(Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks))
- Hematocrit(at 2 and at 7 weeks in the study)
- Red Cell Mass(at 2 and at 7 weeks in the study)
- Necrotizing Enterocolitis, Bells Stage >=2 With Surgery(Birth to initial hospital discharge or to death if it occurs earlier (a median of 94 days))
- Bronchopulmonary Dysplasia Grades 2 or 3(At 36 weeks postmenstrual age)
- Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received(Birth to initial hospital discharge or to death if it occurs earlier (a median of 94 days))
- Intraventricular Hemorrhage Grade I+(Birth to initial hospital discharge or to death if it occurs earlier (a median of 94 days))
- Length of Hospital Stay(At initial hospital discharge or at death if it occurs earlier (a median of 94 days), assessed up to one year of life.)
- Death(Birth, through the 22-26 months corrected age follow-up window, which corresponds to a median of 29 months calendar age in the analysis population)
- Neurodevelopmental Impairment(At 22-26 months corrected age (a median of 25 months corrected age))
- Any Cerebral Palsy(At 22-26 months corrected age (a median of 25 months corrected age))