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卒中的最常见原因之一，是一种急性、单相和推测的颈内动脉远端及其近端分支的炎性动脉病。它有一个积极的自然史，通常进展从轻度动脉不规则在介绍高度狭窄数天内。动脉病变越严重，梗死面积越大，神经功能预后越差。从表现到最严重程度的时间间隔代表了干预和改善结局的机会之窗。目前的治疗包括阿司匹林、支持性治疗和大剂量皮质类固醇，尽管缺乏疗效数据。德尔菲共识确定皮质类固醇治疗FCA的临床试验是国际儿科卒中神经学家的最高研究优先事项。对美国儿科中风研究者的调查也表明，不愿意将FCA儿童随机分配到“无类固醇”组，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，但在初始表现时诊断不确定性的缺点，导致其他卒中病因的儿童不必要的类固醇暴露。临床医生也缺乏与FCA儿童家庭讨论皮质类固醇风险/获益所需的安全性数据。局灶性脑动脉病类固醇（FOCAS）试验的主要目的是比较皮质类固醇治疗疑似FCA的两种策略的有效性：（策略A）立即治疗所有患者，与（策略B）仅选择性治疗证实FCA诊断的疾病进展患者。次要目的是确定皮质类固醇治疗FCA和急性缺血性脑损伤的安全性和耐受性。采用比较有效性试验设计，FOCAS将在25个中心前瞻性入组80名疑似FCA的儿童，表现为动脉缺血性卒中或短暂性脑缺血发作，为期5.5年，并将他们1：1随机分配至策略A或B。主要终点将是影像学结局：FCA严重程度评分从基线至1个月的变化，由设盲的中心神经放射科医生测量，比较在同一扫描仪上进行的MRA。1个月时的梗死体积和6个月时的神经系统结局将是次要终点。FOCAS的安全性结果将解决严重感染和由于类固醇诱导的高血压导致的梗死出血性转化的临床问题。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局。