Renewal of The Mid-America CTSA Consortium (MACC) as a Regional Clinical Center for SIREN - The Mid-America CTSA Consortium (MACC) submits this renewal application to continue as a Regional Clinical Center (RCC) for the “Strategies to Innovate EmeRgENcy Care Clinical Trials” (SIREN) Network (RFA-NS-22-015). Because Dr. Aufderheide (previous Contact PI at the Medical College of Wisconsin [MCW] Hub) has announced his retirement on January 1, 2024, and because his replacement is unknown at the time of grant submission, we propose to transfer the MACC Hub from MCW to the University of Chicago Medicine (UCM) and Contact PI status to David Beiser, MD, MS (UCM) proactively. As recommended by the NIH Project Officer, we are submitting this application as a Renewal, rather than a New application, providing justification for this transfer. The structure of MACC otherwise remains unchanged. Methods: MACC has a proven track record of exemplary patient accrual performance. Despite not having a site within its catchment capable of participating in the HOBIT Trial, MACC is currently tied for 5th highest enroller among 11 Hubs, enrolling 116 subjects (10.0% of total) including 35 subjects (3rd highest) in BOOST-3, 38 subjects (5th highest) in ICECAP, and 43 subjects (6th highest) in C3PO. Patient retention was 98.3% (114/116; 4th highest). This renewal application adds a strategic focus on even greater patient accrual by: 1) investing $10,000/year infrastructure funding in research coordinator support at all 6 MACC sites, 2) a Patient Accrual Liaison (PAL) to proactively identify accrual barriers, 3) rapidly resolving barriers by leveraging CTSA Collaborative Council support, 4) incorporating a Clinical Trial Practicum (entering SIREN patients) into the Clinical Trials Fellowship (CTF) to augment patient accrual, 5) adding 7 new ED expansion sites and 196,455 potential patients/year, and 6) securing an additional $1.71 Million of institutional funds for SIREN. The UCM research team, experienced in supervising Spokes, and the Center for Health and the Social Sciences, experienced in subcontract management, are strong assets. The CTF provides targeted curriculum, over 20% protected time, a Clinical Trial Practicum, K Award submission post completion, and an additional $50,000 institutional funding to train 3, 2- year fellows. All MACC sites agree to continue Reliance and Master Contract Agreements. With a Hub, 5 Spokes, 3 EMS, 4 helicopter systems, catchment of 9,931,200 people, 110,598 potential patients/year, 190 multi- disciplinary collaborators, expansion capacity of 23 adult, 5 pediatric hospitals, and 2 EMS systems, 46 research personnel, 24/7 coverage at all sites, a strategic patient accrual plan, and proven performance, MACC is well- positioned to achieve SIREN goals. Specific Aims. MACC aims to: 1) Meet/exceed recruitment goals of at least 100 subjects per year, including diverse/underserved populations, 2) Achieve all study milestones and exemplary clinical trial execution, 3) Engage a wide spectrum of investigators, 4) Mentor 3 junior faculty investigators to successful academic careers in emergency clinical trial research, 5) Contribute significantly to SIREN governance, and 6) Promote dissemination of SIREN study findings and stimulate SIREN grant applications.