FOcal Cerebral Arteriopathy Steroids (FOCAS) Trial

局灶性脑动脉病类固醇 (FOCAS) 试验

• 批准号: 10529923
• 负责人: MITCHELL S ELKIND
• 金额: $ 177.33万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10529923
• 关键词: Acute; Address; Adrenal Cortex Hormones; Adverse effects; Advocacy; Affect; American; Arterial Disorder; Arteries; Aspirin; Attitude; Benefits and Risks; Blinded; Brain Injuries; Cerebral hemisphere hemorrhage; Characteristics; Chickenpox; Child; Childhood; Childhood stroke; Clinical; Clinical Trials; Communities; Consensus; Dangerousness; Data; Diagnosis; Diagnostic; Disadvantaged; Disease; Disease Progression; Distal; Dose; Early treatment; Enrollment; Etiology; European; Evolution; Family; Goals; Hemorrhage; Herpesviridae; Herpesviridae Infections; Hypertension; Image; Infarction; Infection; Inflammatory; Inflammatory Response; Internal carotid artery structure; International; Ischemic Brain Injury; Ischemic Stroke; Measures; Meta-Analysis; Minority; Motor; Natural History; Neurological outcome; Neurologist; Outcome; Outcome Measure; Patients; Pharmacotherapy; Physicians; Publication Bias; Publishing; Randomized; Randomized, Controlled Trials; Recommendation; Research; Research Personnel; Research Priority; Safety; Severities; Severity of illness; Site; Stenosis; Steroids; Stroke; Structure of trigeminal ganglion; Sum; Supportive care; Surveys; Testing; Time; Training; Transient Ischemic Attack; Uncertainty; Viral; Virus; arm; cerebral arteriopathy; cognitive disability; cohort; comparative effectiveness trial; compare effectiveness; improved outcome; post stroke; preference; prevent; primary endpoint; primary outcome; prospective; randomized placebo controlled trial; safety outcomes; secondary endpoint; secondary outcome; time interval; trial design

Focal cerebral arteriopathy of childhood (FCA)—one of the most common causes of arterial ischemic stroke in a healthy child—is an acute, monophasic, and presumed inflammatory arteriopathy of the distal internal carotid artery and its proximal branches. It has an aggressive natural history, typically progressing from mild arterial irregularity at presentation to high-grade stenosis within days. Greater severity of the arteriopathy correlates with larger infarct size and poorer neurological outcomes. The time interval from presentation to maximal severity represents a window of opportunity to intervene and improve outcomes. Current management includes aspirin, supportive care, and high-dose corticosteroids despite the absence of efficacy data. A Delphi consensus identified a clinical trial of corticosteroids for FCA as the highest research priority amongst international pediatric stroke neurologists. Surveys of U.S. pediatric stroke investigators also indicate an unwillingness to randomize children with FCA to “no steroids,” making a traditional randomized placebo- controlled trial infeasible. The most pressing clinical question is whether to treat all children with suspected FCA immediately or wait and treat only the subset that demonstrate the disease progression characteristic of FCA. Immediate treatment has the potential advantage of preventing FCA progression, but the disadvantage of diagnostic uncertainty at initial presentation, leading to unnecessary steroid exposure in children with other stroke etiologies. Clinicians also lack safety data needed for corticosteroid risk/benefit discussions with families of children with FCA. The primary aim of the Focal Cerebral Arteriopathy Steroid (FOCAS) trial is to compare the effectiveness of two strategies for treating suspected FCA with corticosteroids: (Strategy A) immediate treatment of all patients, versus (Strategy B) selective treatment of only those that demonstrate disease progression confirming the FCA diagnosis. The secondary aim is to determine the safety and tolerability of corticosteroid therapy in the setting of FCA and acute ischemic brain injury. Using a comparative-effectiveness trial design, FOCAS will prospectively enroll 80 children with suspected FCA presenting with arterial ischemic stroke or transient ischemic attack at 25 centers over 5.5 years and randomize them 1:1 to Strategy A or B. The primary endpoint will be an imaging outcome: change in FCA severity score from baseline to 1 month, measured by blinded central neuroradiologists comparing MRAs performed on the same scanner. Infarct volume at 1-month and neurological outcome at 6-months will be secondary endpoints. FOCAS safety outcomes will address clinical concerns for severe infection and hemorrhagic transformation of infarctions due to steroid-induced hypertension. The overall goal is to obtain clinically pertinent evidence that will immediately guide FCA management and help effect better outcomes for children with this dangerous arteriopathy.

儿童局灶性脑动脉病 (FCA) 是健康儿童动脉缺血性中风的最常见原因之一，是一种急性、单相、推测为远端颈内动脉及其近端分支的炎性动脉病，具有侵袭性。动脉病变的严重程度与梗塞面积和神经系统预后较差相关。尽管缺乏疗效数据，但德尔菲共识将皮质类固醇治疗 FCA 的临床试验确定为干预和改善结果的机会窗口。国际儿科中风神经学家的最高研究重点 对美国儿科中风研究人员的调查也表明，他们不愿意将 FCA 儿童随机分组为“不使用类固醇”，这使得传统的随机安慰剂对照试验不可行。最紧迫的临床问题是是否立即治疗所有疑似 FCA 的儿童，还是等待并仅治疗表现出 FCA 疾病进展特征的子集。立即治疗具有预防 FCA 进展的潜在优势，但缺点是初始表现时诊断不确定。 ，导致患有其他中风病因的儿童出现不必要的类固醇暴露，临床医生也缺乏与 FCA 儿童家属讨论皮质类固醇风险/益处所需的安全数据。比较用皮质类固醇治疗疑似 FCA 的两种策略的有效性：（策略 A）对所有患者立即治疗，与（策略 B）仅对那些证实 FCA 诊断的疾病进展的患者进行选择性治疗。次要目的是确定安全性。 FOCAS 采用比较有效性试验设计，前瞻性地招募 80 名患有动脉缺血性中风的疑似 FCA 儿童。 5.5 年内在 25 个中心进行短暂性脑缺血发作，并将其按 1:1 随机分配至策略 A 或 B。主要终点将是影像学结果：FCA 严重程度评分从基线到 1 个月的变化，由盲法中枢神经放射科医生比较执行的 MRA 进行测量1 个月时的梗塞体积和 6 个月时的神经系统结果将是次要终点，这将解决严重感染和出血性转化的临床问题。总体目标是获得临床相关证据，以立即指导 FCA 管理并帮助患有这种危险动脉病的儿童获得更好的结果。