PROJECT SUMMARY (ABSTRACT) Stroke is the second leading cause of death worldwide with an even greater burden of major disability. It occurs at all ages with the greatest incidence in the elderly. The number of strokes is expected to rise in the US and worldwide as the population ages. In 2013, NINDS established NIH Stroke Net to harness the leadership and experience of the stroke research field to efficiently create and complete high-quality, multi-site trials and related biomarker validation and ancillary studies spanning prevention, treatment, and recovery. Since inception, the National Clinical Coordinating Center (NCC) at the University of Cincinnati has provided overall leadership and has coordinated activities within NIH Stroke Net. Our central objective is to engage the broader stroke community to successfully and efficiently design trials that are scientifically important, innovative, and feasible; to start trials expeditiously after being funded by NINDS; to successfully recruit and retain representative participants of the US population, and to maintain a pipeline of new clinical trialists by guiding the training, education, and career development of Stroke Net’s fellows and clinical research professionals. In addition to providing overall leadership and coordination for 24-27 regional coordinating centers affiliated with 500+ potential study sites, the NCC includes the Stroke Net research pharmacy and imaging activities. Our NCC team consists of two MPIs with over 50 years of collective experience designing, implementing, and completing multi-site clinical trials; over 30 NCC staff with in-depth expertise in coordinating, contracting, regulatory, pharmacy and imaging activities; a high level of support from University of Cincinnati; over 20 NCC co-investigators across the US with established expertise in the broad range of cerebrovascular disease and trial methodologies; and numerous international collaborators. From a scientific standpoint, we have established three stroke working groups (acute, prevention and recovery/rehabilitation) that are led by clinical investigator leaders with appropriate expertise from participating Stroke Net sites in the U.S. These working groups offer feedback to the PIs of clinical trial proposals regarding design and feasibility. We have three cores: (1) Fellow Education/Training, (2) Clinical Research Professional (CRP) Education/Training (new), and (3) Diversity, Equity, and Inclusion (new); and four advisory committees: (1) Patient Representation and Advocacy (new), (2) Pediatrics, (3) Preclinical Science (new), and (4) Tele Stroke. The NCC manages Central IRBs at UC and Advarra for all ongoing Stroke Net studies, one of the largest IRB reliance networks in the U.S. The NCC is responsible for clinical trial agreements (CTAs) for participating hospital sites (nearly 1000 CTAs in last five-year cycle), all financial payments to participating sites, and the overall clinical study management of ongoing ...