The CORE-EM Hub Alliance (Coalition for Research in Emergency Medicine) was funded as a SIREN Hub in 2017 to facilitate excellence in resuscitation research. CORE-EM is currently ranked #2 for enrollments within SIREN, and is composed of six, highly experienced, multiple principal investigators (MPIs) and their partner-hubs. This “super-hub” provides the infrastructure for rapid start-up and quality enrollments in large, acute care clinical trials. Supporting a >70-million-person catchment area across the US, CORE-EM prioritizes access to clinical trials for individuals in both urban and rural communities, with attention to serving underrepresented minorities and non-English speaking populations. CORE-EM’s MPI leadership has successfully collaborated for 15+ years to execute clinical trials. MPIs serve on SIREN Governance committees and represent acute care research nationally within the Society for Academic Emergency Medicine, American College of Emergency Physicians, Society for Critical Care Medicine, and through service on NINDS, NCATS, and AHRQ National Advisory Councils. CORE-EM MPIs have assisted in authoring SIREN clinical trials and are actively developing new proposals, such as to study eCPR/ECMO in the Emergency Department (ED) and the use of intravenous glucose-insulin-potassium in pre-hospital and ED settings for acute coronary syndromes. Since being funded in 2017, CORE-EM has successfully deployed trials in cardiology, neurosurgery, infectious disease, hematology, and intensive care. This includes implementing the first two EFIC trials in the states of Rhode Island and Florida. The team rapidly mobilized to deploy SIREN’s COVID-19 C3PO protocol and enrolled the first participants nationally. Co-investigators engage across specialties to ensure excellence in care from scene of injury, through the ED, operating rooms, ICUs, and into rehabilitation. Residents and junior faculty are mentored in the CORE-EM Alliance, as co-investigators and site-PIs; the addition of training funds in 2022 will enhance educational opportunities. For this proposal, CORE-EM will maintain its current six MPI leadership team, who will continue to oversee six partner hubs. Of note, we are pleased to add Virginia Commonwealth University (VCU), including the Richmond Veterans Affairs Medical Center (R-VAMC), as a partner Hub. VCU offers a history of excellence in acute trials dating back to the first EFIC study of cardiac arrest in 2003, and maintains a mature research program in polytrauma, TBI, and spinal cord injury. Under the proposed structure, CORE-EM will provide access to SIREN for participants from rural Maine to the tip of Miami, and across diverse regions of Texas and Arizona. CORE-EM leverages strong leadership, experienced research teams, and a history of successful collaboration. CORE-EM is committed to conducting rigorous trials, training the next generation of physician scientists, and providing outstanding clinical care through excellence in...