Silent Cerebral Infarct Multi-Center Clinical Trial -SCC

无症状脑梗塞多中心临床试验-SCC

• 批准号: 7491017
• 负责人: Bruce A Barton
• 金额: $ 43.89万
• 依托单位: MARYLAND MEDICAL RESEARCH INSTITUTE, INC
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7491017
• 关键词: 12 year old; Accounting; Acute; Affect; Age; Age-Years; Alloimmunization; Archives; Benefits and Risks; Blood; Blood Transfusion; Brain; Brain Injuries; Caring; Cerebral Infarction; Cerebrum; Chest Pain; Child; Childhood; Chronic; Clinical; Clinical Trials; Cognitive; Companions; Condition; Controlled Study; Data; Data Analyses; Data Collection; Data Quality; Detection; Distal; Doctor of Medicine; Documentation; Dropout; Drops; Effectiveness; Enrollment; Ensure; Erythrocytes; Evaluation; Event; Family; Fostering; Glutamic Acid; Goals; Healthcare; Hematology; Hemoglobin; Hemoglobin SS; Hemolytic Anemia; Hospitalization; Hour; Infarction; Infusion procedures; Injury; Internal carotid artery structure; Intervention; Intervention Trial; Iron; Iron Chelating Agents; Ischemic Brain Injury; Lead; Lesion; Magnetic Resonance Imaging; Manuals; Maryland; Master of Public Health; Measurement; Measures; Medical; Monitor; Morbidity - disease rate; Motor; Multi-Institutional Clinical Trial; Neurocognitive; Neurologic; Neurologic Examination; Neurologist; Neurology; Numbers; Operative Surgical Procedures; Paralysed; Parents; Participant; Patients; Performance; Phase; Phase III Clinical Trials; Point Mutation; Population; Positioning Attribute; Preparation; Prevention therapy; Principal Investigator; Procedures; Process; Publications; Purpose; Quality Control; Quality of life; Random Allocation; Randomized; Randomized Controlled Clinical Trials; Rate; Reaction; Recording of previous events; Reporting; Research Design; Research Institute; Research Personnel; Risk; Schedule; Score; Screening procedure; Sickle Cell Anemia; Site; Standardization; Standards of Weights and Measures; Stroke; Stroke prevention; Testing; Thalassemia; Time Study; Training; Transfusion; United States National Institutes of Health; Upper arm; Valine; Veno-Occlusive Disease; Virus Diseases; Week; Work; base; clinical research site; follow-up; middle cerebral artery; mortality; nervous system disorder; prevent; programs; prophylactic; prospective; protocol development; sickling; size; subcutaneous

DESCRIPTION (provided by the applicant): Silent Cerebral Infarct is the most common cause of severe neurological disease in children with Sickle Cell Anemia, occurring in 22% of this population prior to their 16th 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 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 Magnetic Resonance Imaging (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. As many as 3,020 children with Sickle Cell Anemia, greater than 6 years of age and less than 13 years of age, are available to the Clinical Consortium, and will be eligible for screening evaluations. Among this group of eligible patients, approximately 1,880 children will be asked to participate with 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 greater than or equal to 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 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% dropout 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 prevention of stroke or new, Silent Cerebral Infarct assessed by 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）：无症状性脑卒中是镰状细胞贫血儿童严重神经系统疾病的最常见原因，在16岁生日前发生在该人群的22%中。 本试验的总体目标是确定输血治疗是否会进一步降低无症状脑卒中患儿的神经系统发病率，如果是，这种益处的程度。 我们提出了一个多中心，随机试验，22个临床站点，一个临床协调中心，和一个统计协调中心，以测试以下假设：预防性输血治疗儿童无症状脑梗死将导致至少86%的后续明显中风或新的脑梗死，如定义的磁共振成像（MRI）的大脑。 干预是输血治疗与观察，目标是保持输血患者的最大血红蛋白-S浓度低于30%。 多达3,020名6岁以上13岁以下的镰状细胞性贫血儿童可供临床联盟使用，并将有资格接受筛查评估。 在这组符合条件的患者中，约有1，880名儿童将被要求参加脑部MRI。 在这组中，我们估计376名儿童（20%）将患有无症状脑梗塞，其中38名儿童（10%）的TCD测量值升高大于或等于200 cm。秒，并且将不符合研究的资格。 其余338名儿童将有资格随机分配到观察或输血治疗。 基于无症状性脑卒中儿童中60%的父母和儿童接受率，203名参与者（每个治疗分配至少101名）的研究规模确保了90%的把握度，在考虑10%的脱落率和20%的交叉率后，检测到必要的效果，使输血治疗值得推荐（减少86%）。 试验的标准化将在前6个月进行，入组24个月，干预36个月。 入组后12个月，每位患者将接受MRI和TCD检查。 每例研究受试者将在研究退出时（入组后第36个月）接受MRI和认知评估。 本试验的主要目的是确定输血治疗预防卒中或新发无症状脑卒中的有效性，通过脑部MRI评估。 本试验的次要目的是确定：1）预防性输血治疗是否会限制一般智力的进一步下降; 2）在正式的风险-受益分析中，输血治疗无症状脑梗死的总体获益超过了与该治疗相关的风险。 我们预计这项研究的结果可能会导致镰状细胞病和沉默性脑卒中患儿的标准护理实践发生变化。