FOcal Cerebral Arteriopathy Steroids (FOCAS) Trial

局灶性脑动脉病类固醇 (FOCAS) 试验

基本信息

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
项目类别：
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

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

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项目摘要

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.

儿童期局灶性脑型脑病（FCA）是健康儿童中arteal缺血性中风的最常见原因之一 - 是一种急性，单相，并且表现出了独特的颈动脉炎症及其近端分支。它具有侵略性的自然历史，通常从表现时轻度的抗逆规则发展到几天之内的高级狭窄。较高的肌病的严重程度与较大的梗塞大小和较差的神经系统结局相关。从演示到最大严重性的时间间隔代表了干预和改善结果的机会窗口。当前的管理包括阿司匹林，支持性护理和高剂量皮质类固醇，尽管没有效率数据。 Delphi共识确定了FCA皮质类固醇的临床试验是国际小儿中风神经科医生中最高的研究优先级。对美国小儿中风调查人员的调查还表明，不愿随机将FCA的儿童随机为“无立体”，这使得传统的随机安慰剂控制试验是不可行的。最紧迫的临床问题是是否立即治疗所有可疑FCA的儿童，还是仅拭目以待并治疗表现出FCA的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，但是在初次介绍时诊断不确定性的灾难导致其他中风病因的不必要的类固醇暴露。临床医生还缺乏与FCA儿童家庭进行皮质类固醇风险/益处讨论所需的安全数据。局灶性大脑动脉炎类固醇（FOCAS）试验的主要目的是比较两种策略对可疑FCA用皮质类固醇的治疗的有效性：（策略A）立即治疗所有患者，而（策略B）仅对那些证明疾病进展的疾病的选择性治疗。第二个目的是确定在FCA和急性缺血性脑损伤的情况下，皮质类固醇治疗的安全性和耐受性。 Using a comparative-effectiveness trial design, FOCAS will likely 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. 1个月的梗塞体积和6个月时的神经系统结局将是次要终点。灶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违规的出血转化的临床问题。总体目标是获得临床上相关的证据，这些证据将立即指导FCA管理，并为患有这种危险的动脉疾病的儿童提供更好的结果。