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，是远端颈内动脉及其近端分支的急性、单相和推测的炎性动脉病。它具有侵袭性的自然史，通常在几天内从就诊时的轻度动脉不规则发展为高度狭窄。动脉病越严重，梗塞面积越大，神经系统结果越差。从出现症状到最严重的时间间隔代表了干预和改善结果的机会之窗。尽管缺乏疗效数据，但目前的治疗方法包括阿司匹林、支持治疗和大剂量皮质类固醇。德尔菲共识将皮质类固醇治疗 FCA 的临床试验确定为国际儿科中风神经学家的最高研究优先事项。对美国儿科中风研究人员的调查还表明，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，但缺点是初次就诊时诊断不确定，导致患有其他中风病因的儿童出现不必要的类固醇暴露。临床医生还缺乏与 FCA 儿童家庭讨论皮质类固醇风险/益处所需的安全数据。局灶性脑动脉病类固醇 (FOCAS) 试验的主要目的是比较两种用皮质类固醇治疗疑似 FCA 的策略的有效性：（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。第二个目的是确定皮质类固醇治疗在 FCA 和急性缺血性脑损伤中的安全性和耐受性。采用比较有效性试验设计，FOCAS 将在 5.5 年内前瞻性地在 25 个中心招募 80 名疑似 FCA 的儿童，这些儿童出现动脉缺血性中风或短暂性脑缺血发作，并将他们以 1:1 的比例随机分配至策略 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，由盲法中央神经放射科医生比较在同一扫描仪上进行的 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。 FOCAS 安全结果将解决因类固醇引起的高血压引起的严重感染和梗塞出血转化的临床担忧。总体目标是获得临床相关证据，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。