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常见。 这些患者经历了临床上明显的脑血管意外和“无症状梗死”，通过磁共振成像（MRI）证实。 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将安全地减少认知缺陷的发生率和进展，以及纯合子镰状细胞病儿童显性和隐性卒中的易感性。 为了优化未来试验的设计以检验这一假设，我们提出了一项随机、安慰剂对照、双盲的初步研究。 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。确定阿司匹林给药的依从性水平。 2.在一系列适合年龄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，以及分类系统用于组间比较的效用。 5.确定经颅多普勒（TCD）超声速度随时间变化的趋势，以及在组间比较中使用趋势的有效性。 6.获得关于阿司匹林对认知缺陷、影像学异常、明显卒中、疼痛危象和急性胸部综合征发生率影响的初步数据。 7.确定招募患者的可行性。 将入组至少60例患者。 受试者将包括3至10岁的儿童，目前在Galisano儿童医院（罗切斯特大学医学中心，罗切斯特，纽约）和圣卢克-罗斯福医院中心（哥伦比亚大学，纽约，纽约）接受随访的有记录的纯合子镰状细胞病患者。 受试者将被随机分配到两个治疗组之一，每日阿司匹林（1-2.5 mg/kg）。kg./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.