Silent Cerebral Infarct Multi-Center Clinical Trial

无症状脑梗塞多中心临床试验

• 批准号: 7048647
• 负责人: Michael R. DeBaun
• 金额: $ 141.98万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048647
• 关键词: adolescence (12-20); blood transfusion; cerebral ischemia /hypoxia; clinical research; clinical trials; cognition; cooperative study; disease /disorder prevention /control; disease /disorder proneness /risk; functional ability; hemoglobin Ss; human subject; human therapy evaluation; infarct; intelligence tests; longitudinal human study; magnetic resonance imaging; mass screening; medical complication; middle childhood (6-11); nervous system disorder diagnosis; neurologic manifestations; pathologic process; patient oriented research; sickle cell anemia; stroke; stroke therapy

DESCRIPTION (provided by the applicant): Silent Cerebral Infarct (SCI) is the most common cause of severe neurological disease in children with sickle cell anemia, occurring in 22% of this population prior to their 18th birthday. The overall goal of this trial is to determine whether blood transfusion therapy will decrease further neurologic morbidity in children with Silent Cerebral Infarcts and, if so, the magnitude of this benefit. We propose a multi-center, randomized trial with 22 Clinical Sites, a Clinical Coordinating Center, and a Statistical Coordinating Center (see accompanying R01--PI Michael Terrin, MD, MPH) to test the following hypothesis: Prophylactic blood transfusion therapy in children with Silent Cerebral Infarcts will result in at least an 86% reduction in the rate of subsequent overt strokes or new cerebral infarcts, as defined by the MRI of the brain. The intervention is blood transfusion therapy vs. observation, with a goal to keep the maximum hemoglobin-S concentration less than 30% in the transfused patients. Approximately 3,020 children with Sickle Cell Anemia, greater than 6 years of age and less than 13 years of age, will be eligible for screening evaluations. Among this group of eligible patients, approximately 1,880 children will be asked to participate and will receive MRIs of the brain. In this group, we estimate that 376 children (20%) will have Silent Cerebral Infarcts, among whom 38 children (10%) will have an elevated TCD measurement ( 200 cm./sec. and will not be eligible for the study. The remaining 338 children will be eligible for random allocation to either observation or blood transfusion therapy. Based on a 60% parent, and a child acceptance rate among children with Silent Cerebral Infarcts, a study size of 203 participants (at least 101 in each treatment assignment) ensures 90% power to detect the effect necessary to make transfusion therapy worth recommending (86% reduction), after accounting for 10% drop-out and 20% crossover rates. The standardization of the trial will occur during the first six months, enrollment for 24 months, and the intervention for 36 months. Twelve months after enrollment, each patient will receive a MRI and TCD. Each study participant will receive MRI and cognitive assessment at study exit (month 36 after enrollment). The primary aim of this trial is to determine the effectiveness of blood transfusion therapy for the prevention of stroke, or new Silent Cerebral Infarct assessed by the MRI of the brain. The secondary aims of this trial are determining whether: 1) prophylactic blood transfusion therapy will limit further decline in general intellectual abilities; and 2) the overall benefits of blood transfusion therapy for Silent Cerebral Infarcts outweigh risks associated with this therapy in a formal risk-benefit analysis. We anticipate results of this study could lead to a change in standard care practices for children affected with both sickle cell Disease and silent cerebral Infarcts.

描述（由申请人提供）：沉默的脑梗塞（SCI）是镰状细胞贫血儿童严重神经系统疾病的最常见原因，在18岁生日之前发生在该人群的22％。 该试验的总体目的是确定输血疗法是否会降低静音脑梗塞儿童的进一步神经系统发病率，如果是这样，则该益处的幅度。 我们提出了一项具有22个临床部位，一个临床协调中心和一个统计协调中心的多中心，随机试验（请参阅随附的R01--Pi-Pi-Pi-Pi Michael Terrin，MD，MPH），以测试以下假设：预防性的假设：对静音症状的次数均可在86％重新估计的次数均可进行预防性血液交通疗法，并导致静置的次数均可进行。梗塞，由大脑的MRI定义。 干预措施是输血疗法与观察疗法，目的是使输血患者的最大血红蛋白-S浓度低于30％。 大约3,020名患有镰状细胞贫血的儿童大于6岁，年龄少于13岁，将有资格进行筛查评估。 在这组符合条件的患者中，将要求大约1,880名儿童参加并接受大脑MRI。 在这一组中，我们估计有376名儿童（20％）将患有无声的脑梗塞，其中38名儿童（10％）将具有升高的TCD测量值（200 cm./sec。梗塞，研究大小为203名参与者（在每个治疗任务中至少有101个）确保了有90％的功率，以便在预期10％的辍学率和20％的交叉率之后，将其置于24个月和36个月的介入时，才能降低了10％的辍学疗法。 TCD。每个研究参与者将在研究退出时接受MRI和认知评估（入学后的第36个月）。 该试验的次要目的是确定：1​​）预防性输血疗法将限制一般智力能力的进一步下降； 2）在正式的风险效益分析中，输血疗法对静音脑梗塞的总体益处大于与这种疗法相关的风险。 我们预计这项研究的结果可能会导致患有镰状细胞疾病和无声脑梗塞的儿童的标准护理实践发生变化。