Aspirin Prophylaxis in Sickle Cell Disease

描述（由申请人提供）：继发于脑血管损伤的神经系统并发症在纯合子镰状细胞病儿童中很普遍。这些患者经历了临床上明显的脑血管意外和“隐性梗死”，磁共振成像（MRI）证实了这一点。他们也有神经认知异常的风险。我们假设每日低剂量阿司匹林治疗可以安全地减少纯合子镰状细胞病儿童认知缺陷的发生率和进展，以及显性和隐性中风的易感倾向。为了优化未来试验的设计来检验这一假设，我们提出了一项随机、安慰剂对照、双盲的先导研究。该试验的主要目的是评估镰状细胞病儿童每日低剂量阿司匹林的安全性和耐受性。次要目标是：1。建立阿司匹林给药的依从性水平。2. 在一系列与年龄相适应的神经认知测试中确定最有用的评估。3. 评估MRI和磁共振血管造影（MRA）研究的可行性，以及用于组比较的分类系统的实用性。5. 建立经颅多普勒（TCD）超声速度随时间的变化趋势，以及在组间比较中使用趋势的有效性。6. 获得阿司匹林对认知缺陷、影像学异常、明显中风、疼痛危象和急性胸综合征发生率影响的初步数据。确定招募患者的可行性。至少60名患者将被纳入研究。研究对象将包括3至10岁的儿童，他们患有记录在案的纯合子镰状细胞病，目前在加利萨诺儿童医院（罗切斯特大学医学中心，罗切斯特，纽约州）和圣卢克罗斯福医院中心（哥伦比亚大学，纽约，纽约州）进行随访。受试者将随机分为两组，每日服用阿司匹林（1-2.5 mg /kg）。/天)或安慰剂。患者将接受为期18个月的治疗。每3个月将进行仔细的实验室和临床监测，并根据需要进行更频繁的监测。将对治疗前后的临床并发症、神经认知测试、MRI、MRA和TCD研究进行组间比较。

DESCRIPTION (provided by the applicant): Neurologic complications secondary to cerebrovascular damage are prevalent in children with homozygous Sickle Cell Disease. These patients experience both clinically-overt cerebrovascular accidents and "silent infarctions," demonstrated by Magnetic Resonance Imaging (MRI). They are also at risk for neurocognitive abnormalities. We hypothesize that daily, low-dose, aspirin therapy will safely diminish the incidence and progression of cognitive deficits, as well as the pre-disposition to overt and silent stroke in children with homozygous Sickle Cell Disease. In order to optimize the design of a future trial to test this hypothesis, we propose a randomized, placebo-controlled, double-blind pilot study. The trial's primary objective is to evaluate the safety and tolerability of daily low-dose aspirin in children with Sickle Cell Disease. The secondary objectives are: 1. To establish the level of compliance with aspirin administration. 2. To identify the most useful assessments in a battery of age-appropriate neurocognitive tests. 3. To assess the feasibility of MRI and Magnetic Resonance Angiography (MRA) studies, and the utility of classification systems for use in group comparisons. 5. To establish trends in Transcranial Doppler (TCD) ultrasound velocities over time, and the validity of using trends in group comparisons. 6. To obtain preliminary data regarding the effect of aspirin on the incidence of cognitive deficit, imaging abnormalities, overt stroke, painful crises, and Acute Chest Syndrome. 7. To establish the feasibility of recruiting patients. A minimum of 60 patients will be enrolled. Subjects will include children between the ages of 3 and 10 years, with documented homozygous Sickle Cell Disease who are currently followed at the Galisano Children's Hospital (University of Rochester Medical Center, Rochester, New York), and at Saint Luke's-Roosevelt Hospital Center (Columbia University, New York, New York). Subjects will be randomized to one of two treatment groups, daily aspirin (1-2.5 mg./kg./day), or placebo. Patients will receive therapy for 18 months. There will be careful laboratory and clinical monitoring every 3 months, and more frequently as needed. Group comparisons regarding pre- and post-treatment clinical complications, neurocognitive testing, MRI, MRA, and TCD studies will be made.