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)

基本信息

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
项目类别：
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

项目摘要

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 针对严重和易加重哮喘的精准干预 (PrecISE) 网络将开展在目标 1 中，我们建议建立一个国际性的针对严重和易加重哮喘的适应性临床试验。由四个学术机构组成的联盟作为 PrecISE 的临床中心该联盟将由大学领导。加利福尼亚州 (UC) 旧金山哮喘小组（联盟和网站 PI：John Fahy）与三个合作伙伴其他站点 - 加州大学戴维斯分校哮喘研究小组（站点 PI：Nicholas Kenyon）、英国大学哥伦比亚哮喘研究小组（网站 PI：Mark FitzGerald）和莱斯特大学哮喘研究小组（站点 PI：Chris Brightling）都是在临床方面经验丰富的学术站点。严重哮喘的研究，所有这些都对当前疾病知识做出了重要贡献我们共同建议快速招募 100 名重症和哮喘发作患者。易患哮喘的患者参加 PrecISE，我们将实施经 FDA 批准的每个网络范围协议在目标 2 中，我们建议 PrecISE 应采用顺序多重分配。随机试验（SMART）方法在哮喘亚组中进行适应性试验，该亚组由是否存在全身性 IL6 炎症或全身性嗜酸性粒细胞增多，我们特别提出了三个。临床试验中，大约有三分之一的 PrecISE 队列将依次进行试验。托珠单抗和阿那白滞素在高 IL6 哮喘中的疗效试验 #2 将依次测试其疗效。 Mepolizumab 和 Dupilumab 逆转“2 型高”哮喘患者的气流阻塞试验#3 将进行。连续测试多西环素和类固醇戒断对“2-型”患者哮喘控制的效果在所有这些试验中，我们的首要目标是为患有“低”哮喘的患者提供精准医疗。严重形式的哮喘。