Transfusion-Associated Brain Improvement (TABI) trial - CCC

描述(由申请人提供)： 意义：在美国，早产是一个主要的医疗保健问题，美国每周有超过10,000名早产婴儿(怀孕不足37周)出生。2005年，早产给社会造成的经济损失超过260亿美元。幸存者的长期结果往往包括神经发育障碍。在出生体重低于1000克的极低出生体重(ELBW)婴儿中，47%的人在18个月时神经认知评估较低(MDI评分低于70分)，表明存在严重残疾。在重症监护期间，这些婴儿需要进行多次血液测试，而且骨髓不成熟，因此需要频繁输血。然而，在极低出生体重儿中输注最佳的血红蛋白水平以及输注红细胞(RBC)的长期益处和风险在很大程度上是未知的。研究人员和之前的工作：只有两项先前的试验涉及在低出生体重儿中以高或低的血红蛋白阈值输血。他们是由两个临床PI(Kirpalani，Bell)完成的，但得出了关于较高的血红蛋白是否可能改善神经预后的相互矛盾的结果。如果这是真的，一种简单的RBC输注疗法可以用来维持较高的血红蛋白，对ELBW新生儿有潜在的主要好处。这个问题需要在我们在本申请中建议的新审判中进行审查。Kirpalani博士和Bell博士在数据协调中心与DRS Das和Brambilla、PI和Alternate PI合作，在ELBW新生儿的临床试验以及输血医学方面拥有丰富的经验。创新：许多新生儿专家已经转向使用较低的血红蛋白阈值进行输血，这主要是基于回顾数据。我们提出了一项随机对照试验(RCT)来评估输血以维持较高血红蛋白的潜在益处。在新生儿中，评估随机试验的长期结果的必要性是令人信服的。我们的主要结果是矫正年龄18-22个月时死亡或神经发育障碍的综合结果。最后，拟议的研究将考虑到不同的血库做法和多个研究地点分配产品的差异，并将根据不同地点分配的红细胞的红细胞压积的差异进行调整。方法：我们将对低出生体重儿进行随机对照试验，询问：“为了让18-22个月大的婴儿有更好的大脑发育，新生儿ICU中的婴儿应该以较高的血红蛋白阈值还是较低的血红蛋白阈值进行输血？”这个问题与NHLBI的使命高度相关。试验结果可能会从根本上改变新生儿重症监护室的输血做法。环境：我们与NICHD新生儿研究网络(NRN)及其18个临床中心建立了合作伙伴关系。我们相信这项试验是可行的，可以在NRN中心内最有效地进行，NRN中心已经成功地完成了许多有影响力的早产儿临床试验，这些试验经常改变临床实践。 公共卫生相关性： 出生时体重低于1000克的早产儿的长期结局很差，他们的致残率很高。尽管几乎所有这样的婴儿都是输血的，但一些医生比其他医生输血更多，因为基于证据的指南非常广泛。由于较高的输血血红蛋白阈值可能有利于18-22个月的长期神经认知结果，这项随机试验旨在评估保持较高的血红蛋白是否会减少幸存者的死亡或神经残疾。 (摘要结束)

DESCRIPTION (provided by applicant): Significance: Prematurity is a major health care problem in America, with more than 10,000 babies born preterm (less than 37 completed weeks of pregnancy) every week in the US. The economic cost to society of preterm birth in 2005 was more than $26 billion. Long-term outcomes of survivors often include neuro- developmental disabilities. In surviving Extremely Low Birth Weight (ELBW) babies born at less than 1000 g BW, 47% had low neurocognitive assessment (MDI score less than 70) at 18 months, indicating severe handicaps. During intensive care, these babies need many blood tests and have an immature bone marrow, thus requiring frequent blood transfusions. However, what hemoglobin levels to best transfuse at, as well as the long-term benefits and risks of Red Blood Cell (RBC) transfusion in ELBW babies, are largely unknown. Investigators and Prior Work: Only two previous trials addressed whether to transfuse at high or low hemoglobin thresholds in ELBW babies. They were done by the two clinical PIs (Kirpalani, Bell), but produced conflicting results as to whether higher hemoglobins might improve neurological outcome. If this is true, a simple therapy of RBC transfusion could be used to maintain higher hemoglobin, with potential major benefit for ELBW newborns. This question needs to be examined in a new trial, which we propose in this application. Drs. Kirpalani and Bell have joined forces with Drs Das and Brambilla, PI and Alternate PI at the Data Coordinating Center, with vast experience in clinical trials in ELBW neonates, as well as transfusion medicine. Innovation: Many neonatologists have shifted toward using lower hemoglobin thresholds for transfusion, based largely on retrospective data. We propose a randomized controlled trial (RCT) to evaluate the potential benefits of transfusing to maintain higher hemoglobin. The need to assess long-term outcomes of randomized trials is compelling in the newborn. Our primary outcome is a composite of death or neurodevelopmental impairment at 18-22 months of corrected age. Finally, the proposed study will account for differing blood bank practices and differences in dispensed products across multiple study sites and will adjust for variation in the hematocrit of dispensed RBCs by site. Approach: We will perform a RCT in ELBW babies asking: "Should babies in the neonatal ICU get transfused at a higher hemoglobin threshold or a lower one, in order to have better brain development at 18-22 months of age?" The question is highly relevant to the mission of the NHLBI. Trial results could radically alter blood transfusion practices in the neonatal ICU. Environment: We have partnered with the NICHD Neonatal Research Network (NRN) and its 18 clinical centers. We believe this trial is feasible and can be most efficiently conducted within the NRN centers, which have successfully completed many influential clinical trials in preterm infants that have often changed clinical practice. PUBLIC HEALTH RELEVANCE: Long-term outcomes of preterm infants who weigh less than 1000 g at birth are poor, and their disability rates are high. Although virtually all such infants are transfused, some physicians transfuse more than others, because evidence based guidelines are very broad. Since higher hemoglobin thresholds for transfusion may be beneficial to long-term neurocognitive outcomes at 18-22 months, this randomized trial is designed to assess whether keeping hemoglobins higher will reduce death or neurodisability in survivors. (End of Abstract)