Integrated infectious disease and substance use disorder treatment for severe injection-related infections: protocol for the randomized controlled HI-SIRI trial

Hospitalizations for acute bacterial and fungal infections related to injection drug use are increasing in the background of the United States drug overdose crisis. These infections are a significant contributor to morbidity and mortality among people who inject drugs (PWID). Currently, limited comprehensive approaches to caring for PWID hospitalized with severe injection-related infections (SIRIs) exist. We developed a multidisciplinary model integrating infectious disease (ID), substance use disorder (SUD), harm reduction, and patient navigation treatment approaches to help improve outcomes for PWID hospitalized with SIRIs. The Holistic Intervention for Severe Injection-Related Infections (HI-SIRI) trial is a multicenter, randomized controlled trial conducted at six academic hospitals across the United States with two parallel treatment arms. Participants (N = 480) hospitalized with confirmed or suspected SIRI and injection drug use in the past year will be randomized to either the “SIRI team” intervention or treatment as usual (TAU) arm. Randomization will be stratified by site, primary drug (opioid vs. non-opioid), and ICU admission. The primary trial outcome is the difference in the proportion of participants alive with no hospital readmissions at 4 months post-randomization between the two arms. Secondary outcomes include SUD and ID treatment initiation, antibiotic treatment completion, all-cause and substance use related mortality, and overall healthcare utilization, assessed at 8 and 12 months post-randomization. A cost-effectiveness analysis and implementation evaluation will also be performed. The HI-SIRI trial will be one of the first to test a comprehensive treatment approach for the syndemic of PWID hospitalized with acute bacterial and fungal infections. The trial will integrate ID and SUD treatment, built on principles of harm reduction. This innovative model, incorporating evidence-based methods, will address several multi-level barriers to care by offering low-barrier, patient-centered interventions for infection management and substance use treatment. The HI-SIRI trial seeks to transform the current standards of care for PWID hospitalized with SIRI to reduce readmissions, prevent death, and reduce healthcare costs. ClinicalTrials.gov, TRN: NCT05688423, Registration date: 17 January, 2023 ClinicalTrials.gov NCT05688423 (https://www.clinicaltrials.gov/study/NCT05688423). Trial registry name: CTN-0121: Integrated Care and Treatment for SevereInfectious Diseases and Substance Use Disorders (SUD) among HospitalizedPatients. Trial Sponsor: Landhing Moran, PhD, [email protected],National Institute on Drug Abuse Clinical Trials Network. Registration date:January 17, 2023. Protocol Version 4.0.