The NIH SPAN Coordinating Center

NIH SPAN 协调中心

• 批准号: 10339173
• 负责人: Patrick D Lyden
• 金额: $ 65.58万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10339173
• 关键词: NIH; SPAN; Coordinating; Center

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.

我们提出了一种新的，自适应的，安全的系统，并行测试有前途的干预措施，旨在改善结果相比，再灌注单独溶栓，血栓切除术或两者兼而有之。申请人PI和合作者共同拥有数十年使用临床前动物卒中模型的经验。此外，申请人PI和合作者代表联邦政府和各种行业合作伙伴领导了大型和小型多中心和单中心1期、2期和3期临床试验的临床试验协调中心。因此，通过将数十年的动物建模经验和专业知识与临床试验管理相结合，该应用为NINDS提供了一个机会，可以显著提高SPAN指导选择最佳药物的可能性，以过渡到未来可能通过StrokeNet进行的临床试验。申请人PI和合作者了解并参与了许多综述和专题讨论会，这些综述和专题讨论会详细介绍了既往临床前卒中进展的重大失败。基于有利的临床前评估，过多的推定神经保护剂进行临床试验，但在随后的人类中风患者的临床试验中失败。过多的临床失败已经花费了行业和政府数亿美元，浪费了数百名研究人员和协调员的时间，人才和努力。最近成功开发的血栓切除术治疗急性缺血性卒中，激发了重新测试化合物与血栓切除术联合治疗的极大热情。因此，SPAN旨在筛选和选择非常有前途的候选治疗方法，以便在StrokeNet中进行研究。SPAN的成功将为新的、有前途的神经保护剂的成功临床应用提供重要的推动力。在过去的5年里，两个重大进展为神经保护带来了新的希望：具有多种作用机制的化合物的出现，以及颁布了严格的中风治疗候选药物临床前开发的新标准。SPAN的努力提供了一个非常重要的机会，可以找到一种有前途的候选治疗方法，在StrokeNet中进行测试，然后反向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，本申请将通过实施关键技术创新来实现临床前开发的显著改善和进步。我们的合作者神经影像学实验室（LONI）提供的最先进的技术解决方案是安全、稳健、可靠的，并且可以立即实施，因为Lyden博士和Toga博士在RHAPSODY期间合作为研究中心提供了上传图像的交钥匙解决方案（www.LONI.usc.edu）。我们还提出了高度新颖的使用分布式，掩蔽评价。这种新方法允许安全、盲态、成本效益，并内置中央质量控制。