Study protocol for a multicenter, multinational prospective randomized controlled trial comparing outcomes in subjects with Gram-negative bacteremia who have blood culture evaluation using Fast Antibiotic Susceptibility Testing vs. standard of care testing: the FAST trial.

BACKGROUND: Novel, rapid blood culture diagnostics can provide faster antibiotic susceptibility results (AST) compared to standard methods but their impact on clinical outcomes is unclear and not assessed in many prospective clinical trials. METHODS: This study is a two-arm, multicenter, multinational, prospective randomized controlled clinical trial conducted in countries with high antibiotic resistance rates including Greece, India, Israel, and Spain. Nine hundred hospitalized subjects who have blood cultures collected as part of routine clinical care with growth of Gram-negative bacilli (GNB) will be randomized 1:1 to blood culture evaluation using standard of care (SOC) AST vs. a rapid phenotypic AST method, VITEK REVEAL™ in addition to SOC AST. Subjects in both study arms will be reviewed by antibiotic stewardship clinicians who will recommend changes to antibiotic therapy, if indicated. The primary outcome is a composite three-category Desirability of Outcome Ranking (DOOR) defined using three ordered levels: alive without deleterious events, alive with at least one deleterious event, and death. Key secondary outcomes include mortality, length of stay, and time to antibiotic escalation or de-escalation within 3 days of randomization. Exploratory outcomes include a five-category DOOR, categorial agreement between VITEK REVEAL™ and SOC testing, clinician compliance with antibiotic stewardship recommendations, and desirability of treatment selection based on antibiotic spectrum, activity, and bloodstream isolate susceptibility profile (DOOR MAT). The primary analysis will be conducted on the modified intention-to-treat population. DISCUSSION: This trial will evaluate whether use of a rapid phenotypic AST method improves outcomes compared to use of conventional methods for patients with Gram-negative bloodstream infections in clinical settings with high antibiotic resistance rates. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06174649. Registered on Dec 18 2023. PROTOCOL VERSION: Number 20-0021, version 5.0, 11-April-2024.

Duke Scholars

Author Vance Garrison Fowler Jr. Medicine, Infectious Diseases