Sequential, Multiple Assignment, Randomized Trial in Severe Asthma Protocol (SMART-SA)

严重哮喘方案中的序贯、多重分配、随机试验 (SMART-SA)

• 批准号: 10454345
• 负责人: John V Fahy
• 金额: $ 32.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-23 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454345
• 关键词: Adopted; Adrenal Cortex Hormones; Asthma; Biological; Biological Markers; Blood; British Columbia; California; Chronic; Clinical; Clinical Research; Clinical Trials; Data; Data Analyses; Disease; Doctor of Medicine; Doxycycline; Enrollment; Eosinophilia; Firmicutes; Gammaproteobacteria; Goals; Guidelines; Health; IL-6 inhibitor; IL4 gene; IL5 gene; IL6 gene; Infection; Inflammation; Institute of Medicine (U.S.); Interleukin-1; Interleukin-1 Receptors; Interleukin-13; International; Intervention; Knowledge; Lead; Lung; Mucous body substance; National Heart, Lung, and Blood Institute; Obstruction; Outcome; Patient Care; Patients; Persons; Phenotype; Plasma; Precision therapeutics; Predisposition; Protocols documentation; Pulmonary Function Test/Forced Expiratory Volume 1; Reporting; Research; Research Institute; San Francisco; Sequential Multiple Assignment Randomized Trial; Site; Source; Specific qualifier value; Sputum; Steroids; Subgroup; Supervision; Testing; Treatment Failure; Universities; Withdrawal; X-Ray Computed Tomography; adaptive intervention; airway obstruction; anakinra; asthma exacerbation; asthmatic; asthmatic patient; base; biomarker performance; clinical center; cohort; cytokine; design; disorder subtype; dysbiosis; efficacy testing; eosinophil; experience; follow-up; gut microbiome; improved; inhibitor; injured airway; mepolizumab; microbial; molecular subtypes; mucin hypersecretion; novel; obese patients; older patient; patient subsets; personalized intervention; precision medicine; prevent; primary outcome; recruit; respiratory microbiome; response; tocilizumab; trait; treatment guidelines; treatment response; treatment trial

Summary/Abstract The NHLBI Precision Interventions for Severe and Exacerbation Prone Asthma (PrecISE) Network will conduct adaptive clinical trials in severe and exacerbation prone asthma. In Aim 1 we propose to form an international consortium of four academic sites as a clinical center for PrecISE. The consortium will be led by the University of California (UC) San Francisco asthma group (consortium and site PI: John Fahy) in partnership with three other sites - the UC Davis Asthma Research Group (site PI: Nicholas Kenyon), the University of British Columbia Asthma Research Group (site PI: Mark FitzGerald), and the University of Leicester Asthma Research Group (site PI: Chris Brightling). All are academic sites highly experienced in conducting clinical studies in severe asthma, and all have made important contributions to current knowledge about disease mechanisms in asthma. Together, we propose to quickly recruit 100 patients with severe and exacerbation prone asthma for enrollment in PrecISE, and we will implement each network-wide protocol approved by the Steering Committee. In Aim 2 we propose that PrecISE should adopt the sequential multiple assignment randomized trial (SMART) approach to conduct adaptive trials in subgroups of asthmatics defined by the presence or absence of systemic IL6 inflammation or systemic eosinophilia. We specifically propose three clinical trials, each in approximately one third of the 800 person PrecISE cohort. Trial #1 will sequentially test the efficacy of Tocilizumab and Anakinra in IL6-high asthma. Trial #2 will sequentially test the efficacy of Mepolizumab and Dupilumab in reversing airflow obstruction in patients with “type 2-high” asthma. Trial #3 will sequentially test the efficacy of Doxycycline and steroid withdrawal on asthma control in patients with “type 2- low” asthma. In all of these trials, our overarching goal is to advance precision medicine for patients with more severe forms of asthma.

摘要/摘要 NHLBI对严重和易加重哮喘的精确干预(PRECISE)网络将进行 严重和易加重哮喘的适应性临床试验。在目标1中，我们建议成立一个国际 由四个学术站点组成的联合体作为临床研究中心。该财团将由该大学牵头 加州大学旧金山哮喘组织(财团和Site PI：John Fahy)与三家公司合作 其他网站-加州大学戴维斯分校哮喘研究小组(网站PI：Nicholas Kenyon)，英国大学 哥伦比亚哮喘研究小组(网站：Mark Fitzgerald)和莱斯特大学哮喘 研究小组(网站PI：Chris Brightling)。都是具有丰富临床实践经验的学术网站。 对严重哮喘的研究，都对目前对疾病的认识做出了重要贡献 哮喘的发病机制。总之，我们建议迅速招募100名严重和恶化的患者 易感哮喘的注册，我们将执行每个网络范围内的协议批准的 督导委员会。在目标2中，我们提出了PRECISE应采用序贯多重指派 随机试验(SMART)方法在哮喘患者亚组中进行适应性试验 有无全身性IL6炎症或全身性嗜酸性粒细胞增多症。我们特别提出三点建议 临床试验，每项试验在800人精确队列中约三分之一。试验#1将按顺序测试 托西珠单抗与阿那金纳治疗IL-6高水平哮喘的疗效比较试验2将按顺序测试 美波利单抗和度必乐单抗逆转“2型高敏”哮喘患者气流阻塞的疗效。第三次庭审将 序贯试验多西环素与激素停药对哮喘控制的疗效 低“哮喘。在所有这些试验中，我们的首要目标是为更多的患者推进精准医学。 严重的哮喘。