Epo Neuroprotection of ELBW Infants: Planning Grant

描述(申请人提供)：这项计划拨款将用于制定一项详细的研究计划，以便开展一项多中心随机对照试验，使用高剂量重组促红细胞生成素(REPO)作为早期干预措施，改善极低出生体重儿(ELBW)、出生及妊娠29周和出生体重1000g的婴儿的长期神经结局。在过去的二十年里，ELBW婴儿的长期存活率有所提高。然而，由于相对稳定的幸存者比例是受损的，这导致了更多的受损幸存者。主要疾病包括脑瘫、耳聋、失明和智力低下，其中一个或多个问题存在于高达48%的幸存者身上。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，临床用于促进红细胞生成时是安全的。选择极低出生体重儿进行这项研究，是因为他们神经发育不良的风险很高，而且早期高剂量回购具有良好效果的可能性很高。新生儿学的新前沿必须包括开发新的治疗策略，以改善这些脆弱婴儿的神经学结果。这项提案的资金将使我们能够规划一种新的神经保护方法。这种临床试验的成功将对我们儿童及其家庭的健康和福祉产生重大影响，还将产生重要的经济利益，因为早产儿使用了我们医疗保健和教育资金中不成比例的份额。我们汇集了来自全美11个中心的专家小组来计划和执行这项研究。所有研究人员都对神经发展和临床试验有经验和兴趣。纳入这些中心将确保纳入足够多的患者，并且受试者之间存在多样性，因此结果可以推广。为了启动一项成功的多中心随机对照临床试验，在试验开始之前必须准备好许多细节。这笔赠款的预期产品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。第三阶段试验的赠款也将在规划赠款的最后6个月内寻求。 公共卫生相关性：将制定一项详细的研究计划(包括完整的操作和程序手册)，以开展大剂量重组促红细胞生成素(REPO)的多中心随机对照试验，作为早期干预措施，改善出生体重1000g的极低出生体重儿(ELBW)的长期神经结局。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(高达48%)，而且早期高剂量回购具有良好效果的可能性很高。这种临床试验的成功将对我们儿童及其家庭的健康和福祉产生重大影响，还将产生重要的经济利益，因为早产儿使用了我们医疗保健和教育资金中不成比例的份额。

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.