Transfusion-Associated Brain Improvement (TABI) trial - CCC

描述（由申请人提供）： 重要性：早产是美国的一个主要卫生保健问题，在美国每周有超过10，000名婴儿早产（怀孕不到37周）。2005年，早产给社会造成的经济损失超过260亿美元。幸存者的长期结果通常包括神经发育障碍。在出生时体重低于1000 g的极低出生体重（ELBW）存活婴儿中，47%在18个月时神经认知评估（MDI评分低于70）较低，表明存在严重障碍。在重症监护期间，这些婴儿需要多次血液检查，并且骨髓不成熟，因此需要频繁输血。然而，什么样的血红蛋白水平最好输注，以及红细胞（RBC）输注在ELBW婴儿中的长期益处和风险，在很大程度上是未知的。研究者和先前的工作：只有两个先前的试验解决了是否在ELBW婴儿的高或低血红蛋白阈值输血。由两名临床PI（Kirpalani，Bell）完成，但对于较高的血红蛋白是否可能改善神经学结局产生了相互矛盾的结果。如果这是真的，一个简单的红细胞输注疗法可以用来维持较高的血红蛋白，与ELBW新生儿的潜在重大利益。这个问题需要在我们在本申请中提出的新的试验中进行审查。Kirpalani博士和Bell博士与数据协调中心的Das博士和Brambilla博士、PI和候补PI联手，在ELBW新生儿临床试验以及输血医学方面拥有丰富的经验。创新：许多新生儿科医生已转向使用较低的血红蛋白阈值进行输血，这主要是基于回顾性数据。我们提出了一个随机对照试验（RCT），以评估潜在的好处，补充使用，以维持较高的血红蛋白。在新生儿中评估随机试验的长期结果的需求是迫切的。我们的主要结局是在矫正年龄18-22个月时死亡或神经发育障碍的复合终点。最后，拟定的研究将考虑不同血库实践和多个研究中心分发产品的差异，并将调整各研究中心分发RBC的红细胞压积变化。方法：我们将在ELBW婴儿中进行随机对照试验，询问：“新生儿ICU中的婴儿应该以较高的血红蛋白阈值或较低的血红蛋白阈值输血，以便在18-22个月大时有更好的大脑发育？“这个问题与NHLBI的使命高度相关。试验结果可能从根本上改变新生儿ICU的输血实践。环境：我们与NICHD新生儿研究网络（NRN）及其18个临床中心合作。我们相信这项试验是可行的，并且可以在NRN中心内最有效地进行，这些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。

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.