CTN-0121 UM Supplement Request PROJECT SUMMARY/ABSTRACT This application is to request supplement funds for FY25 for CTN-0121: Integrated Care and Treatment for Severe Infectious Diseases and Substance Use Disorders (SUD) among Hospitalized Patients. The CTN 0121 study is a two-group, randomized controlled trial conducted in six hospitals across the U.S. designed to test the effectiveness of an integrated infectious diseases (ID)/substance use disorder (SUD) clinical team intervention approach on improving health outcomes for patients hospitalized with severe injection-related infections (SIRI) and who endorse injection drug use. The single primary objective of this trial is to determine whether an integrated SUD and ID care team intervention (SIRI Team) that begins in the hospital and extends after hospital discharge will be associated with lower mortality and fewer hospital readmissions for patients with the SIRI Team than with Treatment as Usual (TAU). The primary hypothesis is that the proportion of participants alive with no hospital readmissions will be higher in the SIRI Team intervention group vs. TAU group at four months post-randomization. Secondary objectives are to examine differences between the two study groups in important milestones that may contribute to post discharge recovery, harm reduction, and sustained health: proportion of participants alive with no hospital readmissions utilizing all time points (4, 8, and 12 months post- randomization) to ascertain whether differences maintain during longer-run follow-up, completion of antibiotic course, initiation of other treatment by hospital discharge, receipt of outpatient care post-discharge, retention in or completion of outpatient care, and change in substance use severity and frequency. The CTN 0121 study has been developed and is led nationally by the Florida Node Alliance (FNA). The study builds on the FNA’s record of success in leading and implementing trials in healthcare settings and integrating substance use into mainstream healthcare and is consistent with the FNA’s aim of delivering integrative models of care for comorbid SU and HIV in hospital settings (AIM2). The FNA collaborates with other Nodes on the design and implementation of CTN trials by providing the infrastructure and capabilities required for successful study execution.