Transfusion-Associated Brain Improvement (TABI) trial - CCC

输血相关大脑改善 (TABI) 试验 - CCC

• 批准号: 8849489
• 负责人: EDWARD F BELL
• 金额: $ 24.01万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8849489
• 关键词: Accounting; Address; Age; Age-Months; Americas; Apnea; Benefits and Risks; Bilateral Hearing Loss; Birth; Birth Weight; Blood Banks; Blood Tests; Blood Transfusion; Bone Marrow; Brain; Bronchopulmonary Dysplasia; Cephalic; Cerebral Palsy; Cessation of life; Child; Childhood; Classification; Clinical; Clinical Trials; Cochlear Implants; Cognitive; Conflict (Psychology); Consent; Cost-Benefit Analysis; Data; Data Coordinating Center; Development; Developmental Disabilities; Disabled Persons; Environment; Epilepsy; Erythrocyte Transfusion; Erythrocytes; Extremely Low Birth Weight Infant; Eye; Feeds; Follow-Up Studies; Gestational Age; Head circumference; Healthcare; Hematocrit procedure; Hemoglobin; Hemoglobin concentration result; Hydrocephalus; Immature Bone; Impairment; Incidence; Individual; Infant; Infant Development; Influentials; Intensive Care; Intention; Iowa; Language; Lead; Length; Length of Stay; Long-Term Survivors; Lung diseases; Masks; Medicine; Microcephaly; Mission; Morbidity - disease rate; Motor; Movement; Multicenter Neonatal Research Network; Muscle Tonus; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; Necrotizing Enterocolitis; Neonatal Intensive Care Units; Neurocognitive; Neurodevelopmental Impairment; Neurologic; Neurological outcome; Newborn Infant; Ophthalmologist; Outcome; Outcome Study; Pathway interactions; Periventricular Leukomalacia; Physicians; Pregnancy; Premature Birth; Premature Infant; Randomized; Randomized Controlled Trials; Regimen; Research; Research Personnel; Retinopathy of Prematurity; Risk; Shunt Device; Site; Societies; Staging; Survival Rate; Survivors; Time; Training; Transfusion; Ultrasonography; Variant; Vision; Visual Acuity; Weight; Work; abstracting; arm; base; blood product; central nervous system injury; clinical practice; clinically relevant; design; disability; economic cost; evidence based guidelines; experience; follow-up; handicapping condition; hearing impairment; improved; innovation; intraventricular hemorrhage; motor impairment; neonate; premature; primary outcome; randomized trial; secondary outcome; tool

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.

描述（由申请人提供）： 意义：早产是美国的一个主要医疗保健问题，美国每周有超过 10,000 名早产婴儿（怀孕不足 37 周）。 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。在体重低于 1000 克的幸存极低出生体重 (ELBW) 婴儿中，47% 在 18 个月时神经认知评估较低（MDI 评分低于 70），表明存在严重障碍。在重症监护期间，这些婴儿需要进行多次血液检查，并且骨髓尚未成熟，因此需要频繁输血。然而，对于 ELBW 婴儿的最佳输血血红蛋白水平以及红细胞 (RBC) 输注的长期益处和风险，目前尚不清楚。研究人员和之前的工作：之前只有两项试验探讨了 ELBW 婴儿是否应在高血红蛋白阈值或低血红蛋白阈值下进行输血。它们是由两位临床 PI（Kirpalani、Bell）完成的，但对于较高的血红蛋白是否可以改善神经系统结果产生了相互矛盾的结果。如果这是真的，那么简单的红细胞输注疗法可用于维持较高的血红蛋白，这对 ELBW 新生儿具有潜在的重大益处。这个问题需要在我们在本申请中提出的新试验中进行检验。博士。 Kirpalani 和 Bell 与数据协调中心的 PI 和候补 PI Das 和 Brambilla 博士联手，他们在 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：许多新生儿科医生主要基于回顾性数据，转向使用较低的血红蛋白阈值进行输血。我们提出一项随机对照试验（RCT）来评估输血以维持较高血红蛋白的潜在益处。对于新生儿来说，评估随机试验的长期结果是非常有必要的。我们的主要结局是校正年龄 18-22 个月时死亡或神经发育障碍的综合结果。最后，拟议的研究将考虑多个研究地点不同的血库实践和分配产品的差异，并将根据地点分配的红细胞的血细胞比容变化进行调整。方法：我们将对 ELBW 婴儿进行随机对照试验，询问：“新生儿 ICU 中的婴儿应该以更高还是更低的血红蛋白阈值进行输血，以便在 18-22 个月大时获得更好的大脑发育？”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，这些试验常常改变了临床实践。