The NIH SPAN Coordinating Center

NIH SPAN 协调中心

基本信息

批准号：
10074917
负责人：
Patrick D Lyden
金额：
$ 16.7万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10074917
关键词：
Acute Address Alteplase Animal Model Animals Appearance Award Awareness Back Behavior Behavioral Blinded Cerebral hemisphere hemorrhage Clinical Clinical Trials Clinical assessments Coagulation Process Consultations Data Databases Development Doctor of Philosophy Evaluation Failure Federal Government Funding Futility Future Goals Government Grouping Hemorrhage Histologic Histology Human Image Individual Industry Infrastructure Ischemia Ischemic Stroke Knowledge Laboratories Lead Leadership Lesion Masks Measures Middle Cerebral Artery Occlusion Modeling Mus National Institute of Neurological Disorders and Stroke Neuroprotective Agents Oryctolagus cuniculus Outcome Outcome Assessment Personal Communication Phase Preclinical Testing Procedures Production Quality Control Rattus Reperfusion Therapy Research Personnel Scanning Secure Site Specific qualifier value Stroke System Talents Testing Thrombectomy Time Training United States National Institutes of Health arm base behavior test behavioral outcome cost cost efficient design drug testing experience flexibility improved outcome industry partner innovation neuroimaging neuroprotection novel novel strategies phase 2 testing pre-clinical preclinical development preclinical study primary outcome programs secondary outcome stroke model stroke patient stroke recovery stroke therapy success symposium therapy design thrombolysis

项目摘要

Abstract We propose a novel, adaptive, secured system for parallel testing of promising interventions designed to improve outcome compared to reperfusion alone with thrombolysis, thrombectomy or both. The applicant PI and collaborators together have decades of experience using preclinical animal stroke models. Also, and perhaps uniquely, the applicant PI and collaborators have led clinical trial coordinating centers for large and small multi‐center and single center Phase 1, 2, and 3 clinical trials on behalf of the Federal Government and various industry partners. Thus, by combining decades of experience and expertise in animal modeling with clinical trial management this application affords NINDS an opportunity to significantly enhance the likelihood that SPAN will guide the selection of the best agent(s) to transition to future clinical trials likely to be conducted through StrokeNet. The applicant PI and collaborators are aware of, and have participated in, many reviews and symposia detailing the significant failures of previous preclinical stroke development. A plethora of putative neuroprotectants proceeded to clinical trial based on favorable preclinical assessment, only to fail in subsequent clinical trials of human stroke patients. The plethora of clinical failures has cost industry and governments hundreds of millions of dollars and wasted the time, talent, and effort of hundreds of investigators and coordinators. The recent successful development of thrombectomy for acute ischemic stroke generated considerable enthusiasm for re‐testing compounds in combination with thrombectomy. Thus, SPAN is intended to screen and select highly promising candidate treatments for possible study in StrokeNet. A success in SPAN will provide a significant impetus to renew efforts toward successful clinical deployment of novel, promising neuroprotectants. In the past 5 years, two significant developments raise new hope for neuroprotection: the appearance of compounds with multiple mechanisms of action, and the promulgation of new standards for the rigorous preclinical development of stroke treatment candidates. The SPAN effort affords the highly significant opportunity to find a promising candidate treatment, test it in StrokeNet, and then back‐validate the ideal preclinical testing paradigm that predicts success in clinical trials. This present application, if funded, will achieve significant improvement and advancement of preclinical development by implementing critical technical innovations. The state‐of‐the‐art technical solution offered by our collaborator, the Laboratory of Neuroimaging (LONI) is secure, robust, reliable, and ready to implement immediately because Drs. Lyden and Toga collaborated during RHAPSODY to provide sites a turn‐key solution for uploading images (www.LONI.usc.edu). We also propose the highly novel use of distributed, masked evaluation. This novel approach allows for a secure, blinded, cost efficient, with built in central quality‐control.

抽象的我们提出了一种新颖的、自适应的、安全的系统，用于并行测试有希望的干预措施，旨在改善申请人 PI 和合作者与单独再灌注联合溶栓、血栓切除术或两者的结果进行比较。申请人也拥有数十年使用临床前动物中风模型的经验。 PI和合作者领导了大大小小的多中心和单中心1期临床试验协调中心，代表联邦政府和各个行业合作伙伴进行的 2 项和 3 项临床试验，结合了数十年的经验。在动物建模和临床试验管理方面的经验和专业知识该应用程序为 NINDS 提供了显着提高 SPAN 指导选择最佳代理以过渡到的可能性的机会未来将通过 StrokeNet 进行的临床试验申请人 PI 和可能的合作者已了解并已了解。参加了许多回顾和研讨会，详细介绍了先前临床前中风发展的重大失败。基于有利的临床前评估，大量假定的神经保护剂进入了临床试验，但都失败了在随后对人类中风患者进行的临床试验中，大量的临床失败给行业和政府带来了损失。数亿美元，浪费了数百名调查员和协调员的时间、人才和精力。最近成功开发的用于治疗急性缺血性中风的血栓切除术引起了人们的极大热情因此，SPAN 旨在筛选和选择高度有前途的化合物。 StrokeNet 可能研究的候选治疗方法 SPAN 的成功将为更新提供重要动力。在过去的 5 年里，有两个重大的进展，以实现新型、有前景的神经保护剂的成功临床部署。为神经保护带来新的希望：具有多种作用机制的化合物的出现，并颁布新标准以严格开发中风治疗候选药物的临床前。 SPAN 的努力提供了非常重要的机会来寻找有前途的候选治疗方法，并在 StrokeNet 中对其进行测试，然后回溯验证预测临床试验成功的理想临床前测试范式。如果获得资助，该申请将通过以下方式实现临床前开发的重大改进和进步实施我们的合作者提供的最先进的技术解决方案。神经影像实验室 (LONI) 安全、稳健、可靠，并且可以立即实施，因为 Lyden 博士。和 Toga 在 RHAPSODY 期间合作，为网站提供上传图像的统包解决方案 (www.LONI.usc.edu)。我们还提出了分布式、屏蔽评估的高度新颖的使用，这种新颖的方法可以实现安全、可靠的评估。盲法、成本效益高、内置中央质量控制。