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的儿童中很常见。这些患者既经历了临床上明显的脑血管意外，也经历了磁共振成像(MRI)显示的“无症状脑梗塞”。他们还面临神经认知异常的风险。我们假设，每天小剂量的阿司匹林治疗将安全地减少认知障碍的发生率和进展，以及纯合子镰状细胞病儿童显性和静止性中风的易感性。为了优化未来试验的设计以检验这一假说，我们提出了一项随机、安慰剂对照、双盲的先导性研究。这项试验的主要目标是评估每日小剂量阿司匹林对患有镰刀细胞病的儿童的安全性和耐受性。次要目标是：1。建立阿司匹林服药依从性水平。2.在一系列适合年龄的神经认知测试中找出最有用的评估。3.评估MRI和磁共振血管成像(MRA)研究的可行性，以及分类系统在组间比较中的应用。5.建立经颅多普勒(TCD)超声速度随时间的趋势，以及在组比较中使用趋势的有效性。6.获得有关阿司匹林对认知障碍、影像异常、明显中风、疼痛危象和急性胸腔综合征发生率的影响的初步数据。7.确定招收病人的可行性。最少将有60名患者入选。受试者将包括3至10岁的儿童，他们患有已证实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，纽约)和圣卢克-罗斯福医院中心(哥伦比亚大学，纽约，纽约)进行跟踪观察。受试者将被随机分成两组，每日服用阿司匹林(1-2.5毫克/公斤/天)或安慰剂。患者将接受为期18个月的治疗。将每3个月进行一次仔细的实验室和临床监测，并根据需要进行更频繁的监测。将对治疗前和治疗后的临床并发症、神经认知测试、MRI、MRA和TCD研究进行组内比较。

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.