Epo Neuroprotection of ELBW Infants: Planning Grant

描述（由申请人提供）：该计划资助将用于制定详细的研究计划，以开展一项多中心随机对照试验，将高剂量重组促红细胞生成素（rEpo）作为早期干预，以改善极低出生体重婴儿（ELBW）、妊娠<29周和d1000g婴儿的长期神经预后。在过去的二十年中，ELBW婴儿的长期存活率有所提高。然而，由于残障幸存者的比例相对恒定，因此残障幸存者的数量较多。主要发病率包括脑瘫、耳聋、失明和智力迟钝，高达48%的幸存者存在上述一种或多种问题。目前还没有针对ELBW婴儿的神经保护治疗方法。rEpo在脑损伤模型中具有神经保护作用，临床上用于促进红细胞生成是安全的。选择ELBW婴儿进行这项研究，是因为他们神经发育不良的风险很高，而且早期高剂量的rEpo很可能会产生有益的效果。新生儿科的新前沿必须包括开发新的治疗策略，以改善这些易感婴儿的神经预后。这项提案的资金将允许对神经保护的新方法进行规划。这种临床试验的成功将对我们的儿童及其家庭的健康和福祉产生重大影响，并将产生重要的经济效益，因为早产儿使用了我们的医疗保健和教育资金的不成比例的份额。我们召集了一组来自美国11个中心的专家来计划和执行这项研究。所有研究者都对神经发育和临床试验有经验和兴趣。纳入这些中心将确保有足够多的患者被纳入，并且受试者之间存在多样性，因此结果可以普遍化。为了成功地开展多中心随机对照临床试验，必须在试验开始前确定许多细节。这项拨款的预期成果是一份详细的临床试验研究计划，包括一份完整的操作和程序手册。第三期试验的拨款也将在该计划拨款的最后6个月内寻求拨款。

DESCRIPTION (provided by applicant): This planning grant will be used to develop a detailed research plan in order to carry out a multicenter randomized controlled trial of high dose recombinant erythropoietin (rEpo) as an early intervention to improve long-term neurological outcomes in extremely low birth weight infants (ELBW), those born <29 weeks of gestation, and d1000g. Long-term survival of ELBW infants has improved over the last two decades. However, since a relatively constant proportion of survivors are impaired, this has resulted in a larger number of impaired survivors. Major morbidities include cerebral palsy, deafness, blindness, and mental retardation, and one or more of these problems is present in up to 48% of survivors. There are currently no neuroprotective treatments available for ELBW infants. rEpo has neuroprotective effects in models of brain injury, and is safe when used clinically to promote erythropoiesis. ELBW infants were chosen for this study because of their high risk of poor neurodevelopmental outcome, and the high likelihood that early high dose rEpo will have a beneficial effect. The new frontier of neonatology must include development of new treatment strategies that improve the neurological outcomes of these vulnerable infants. Funding of this proposal will allow for the planning of a novel approach to neuroprotection. Success of such a clinical trial will have a major impact on the health and well being of our children, their families, and will also have important economic benefits, since preterm infants utilize a disproportionate share of our health care and education dollars. We have put together a group of experts from eleven centers across the United States to plan and execute this study. All investigators have experience and interest in neurodevelopment and with clinical trials. The inclusion of these centers will insure that enough patients are enrolled, and that there is diversity among subjects so the results can be generalized. In order to launch a successful multicenter randomized controlled clinical trial, many details must be in place before the trial begins. The expected product of this grant is a detailed clinical trial research plan including a complete manual of operations and procedures. Grant funding for the phase III trial will also be sought during the last 6 months of this planning grant. PUBLIC HEALTH RELEVANCE: A detailed research plan (including a complete manual of operations and procedures) will be formulated in order to carry out a multicenter randomized controlled trial of high dose recombinant erythropoietin (rEpo) as an early intervention to improve long-term neurological outcomes in extremely low birth weight infants (ELBW), those born d1000g. ELBW infants were chosen for this study because of their high risk of poor neurodevelopmental outcome (up to 48%), and the high likelihood that early high dose rEpo will have a beneficial effect. Success of such a clinical trial will have a major impact on the health and well being of our children, their families, and will also have important economic benefits, since preterm infants utilize a disproportionate share of our health care and education dollars.