The NIH SPAN Coordinating Center

NIH SPAN 协调中心

• 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
• 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

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.

摘要 我们提出了一种新的、自适应的、安全的系统，用于并行测试有希望的干预措施，旨在改进 结果与单纯再灌注加溶栓、取栓或两者同时进行比较。申请者派和合作者 共同拥有数十年使用临床前动物中风模型的经验。还有，也许是独一无二的，申请者 PI及其合作者领导了大小多中心和单中心一期临床试验协调中心， 代表联邦政府和各种行业合作伙伴进行2项和3项临床试验。因此，通过结合几十年来的 在动物建模和临床试验管理方面的经验和专业知识这一应用程序为NINDS提供了 显著提高斯潘指导最佳经纪人(S)过渡的可能性的机会 未来的临床试验可能会通过StrokeNet进行。申请者PI和合作者知道并拥有 参与了许多回顾和研讨会，详细介绍了先前临床前中风开发的重大失败。 基于良好的临床前评估，过多的假定神经保护剂进行了临床试验，但都以失败告终。 在随后的人类中风患者的临床试验中。过多的临床失败让工业界和政府付出了代价 数亿美元，浪费了数百名调查人员和协调员的时间、才华和努力。 最近成功开发的血栓摘除术治疗急性缺血性中风引起了相当大的热情 结合血栓切除术重新测试化合物。因此，SPAN旨在筛选和选择非常有前途的 StrokeNet上可能研究的候选治疗方法。SPAN的成功将为更新提供巨大的推动力 为成功部署新型、有前途的神经保护剂所做的努力。在过去的5年里，有两个重要的 发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， 并颁布了新的标准，以严格开发中风候选治疗的临床前阶段。这个 SPAN的努力提供了非常重要的机会，可以找到有前景的候选治疗方法，在StrokeNet中进行测试， 然后对预测临床试验成功的理想临床前测试范例进行反向验证。这份礼物 如果获得资金，应用程序将通过以下方式显著改善和推进临床前开发 实施关键技术创新。我们的合作者提供最先进的技术方案 神经成像实验室(LONI)是安全、可靠、可靠的，并且可以立即实施，因为Lyden博士 Toga在Rhapsody期间合作，为网站提供上传图片的交钥匙解决方案(www.LONI.usc.edu)。 我们还提出了分布式掩蔽评估的高度新颖的使用。这种新颖的方法允许安全、 盲目、高性价比、内置中央质量控制。