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. 2025 Nov 12;26(1):500.
doi: 10.1186/s13063-025-09228-4.

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

Ritu Banerjee  1 , Lauren Komarow  2 , Yixuan Li  2 , Qihang Wu  2 , Lucia Sanchez-Gonzalez  2 , Donald Mau  3 , Erin Abbenante  3 , Nyssa Schwager  3 , Andrew Dodd  3 , Maria Souli  3 , Holly S Geres  3 , Sarah Doernberg  4 , Kerryl Greenwood-Quaintance  5 , Scott R Evans  2 , Henry F Chambers  4 , Vance G Fowler Jr  3 , Robin Patel  5 ; Antibacterial Resistance Leadership Group
Affiliations

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

Ritu Banerjee et al. Trials. .

Abstract

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.

Keywords: Antibiotic susceptibility testing; Bacteremia; Bloodstream infection; Gram-negative.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate {24}: The study protocol will be reviewed by each site’s relevant local IRB prior to participation. We will request a waiver of informed consent from each site. If local and/or national regulations do not allow a waiver of consent, a locally approved consent process will be utilized. To ensure subject confidentiality and privacy, database access will be limited to study personnel who are issued a unique user identification and password. Data will be entered at each site by study personnel. The study protocol, documentation, data, and all other information generated will be held in strict confidence. Consent for publication {32}: Consent for publication was sought and approved by all listed authors who have no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the sponsor. The investigators have adhered to the policies for the protection of human subjects as prescribed in AR 70–25. Competing interests {28}: The authors report the following outside financial activities: Dr. Patel reports grants from MicuRx Pharmaceuticals and bioMérieux. Dr. Patel is a consultant to PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., HealthTrackRx, bioMérieux and CARB-X. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, and a patent on an anti-biofilm substance issued. Dr. Patel receives honoraria from Up-to-Date and the Infectious Diseases Board Review Course. Dr. Doernberg reports grants from Gilead, Pfizer, F2G, Regeneron, Chan Zuckerberg Biohub, PCORI, and NIAID/NIH and is a consultant to Genentech, Janssen, Shinogi, and Basilea. Dr. Doernberg has a patent on therapeutic use of a Mif agonist. Dr. Evans reports grants from NIH and the Centers for Disease Control and Prevention and receives consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson &Johnson, Endologix, ChemoCentryx, Becton Dickenson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Develoment Institute, SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and IDDI, and honoraria from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the U.S. Food and Drug Administration. Dr. Evans participates in Data Safety and Monitoring Boards or Advisory Boards for NIH, BARDA, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, Abbvie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, and Novartis. Dr. Fowler reports grants from NIH, Merck, Contrafect, Karius, Basilea, Janssen, AstraZeneca, and EDE. He receives honoraria from Up-to-Date, consulting fees from Akagera, AstraZeneca, Armata, Basilea, Debiopharm, GSK, and Integrated Biotherapeutics, has a patent on a sepsis diagnostic, and stock options in Valanbio. All other authors declare no conflicts of interest. The trial design was not affected by any external relationships with companies.

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