Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial (FAST)

This study is a 2-arm, multicenter, multinational, prospective, randomized, controlled clinical trial. Hospitalized subjects with blood cultures growing Gram negative bacilli (GNB) will be randomized 1:1 to have the positive blood cultures characterized using standard of care (SOC) antimicrobial susceptibility testing (AST) vs. a rapid AST method known as Reveal™ in addition to SOC AST. The purpose of the FAST trial is to evaluate whether use of a rapid phenotypic AST improves clinical outcomes compared to use of SOC AST methods in clinical settings with high resistance rates.

Study Overview

• Status: Completed
• Conditions: Bloodstream Infection; Gram-negative Bacteremia
• Intervention / Treatment: Diagnostic test: Reveal

• Study Type: Interventional
• Enrollment (Actual): 900
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Piraeus, Greece, 18536
    • Tzaneio General Hospital
  • Attiki
    • Chaidari, Attiki, Greece, 12462
      • Attikon University General Hospital
• India
  • Mangalore
    • Attavara, Mangalore, India, 575001
      • Kasturba Medical College, Mangalore
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Kfar Saba, Israel, 4428162
    • Meir Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Spain
  • La Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña (CHUAC) Sergas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Positive blood culture with Gram stain showing GNB
2. Hospitalized at the time of Gram stain result
3. Enrolled within 16 hours of blood culture positivity

Exclusion Criteria:

1. Positive blood culture for GNB within the prior 7 days (if known at the time of Gram stain result)
2. Deceased at the time of Gram stain result
3. Gram-positive bacilli, Gram-positive cocci, Gram-negative cocci, yeast, fungi, or multiple morphologies of GNB detected on Gram stain of blood culture
4. Previous enrollment in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; When a blood culture growing GNB is randomized standard of care arm the positive blood cultures will be characterized using standard of care antimicrobial susceptibility testing (AST)
Active Comparator: Reveal; When a blood culture growing GNB is randomized to the Reveal arm, the positive blood culture will be characterized using Reveal, a rapid AST, and the standard of care AST.	Diagnostic test: Reveal; Reveal is a rapid AST method, which uses small molecule sensor technology to detect growth of bacterial populations by measuring volatile metabolites, and provides AST results in ~5 hours. Reveal™ is approved for clinical use in the European Union (EU) and Israel and approval is in process in India, and provides minimum inhibitory concentrations (MICs) for 28 antibiotics and 9 Gram negative species, that together account for ~90% of organisms causing Gram negative blood stream infections (BSI).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject Clinical Outcomes, as measured by Desirability of Outcome Ranking (DOOR)	The composite 3-category DOOR outcome will assess three deleterious events (unsuccessful discharge, lack of clinical response, and undesirable events) in addition to survival up to 30 days after Gram stain result. The primary DOOR outcome measure is defined using three ordered levels. From best to worst, they are: Alive without deleterious events; Alive with at least 1 deleterious event; Death	Up to 30 days after Gram stain result

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Mortality	All-cause in-hospital mortality up to 30 days post Gram stain result	Up to 30 days post Gram Stain
Hospital Stay Length	Length of index stay in the hospital up to 30 days post Gram stain result, for those subjects alive at 30 days. Length of stay will be calculated as date of discharge minus date of Gram stain result.	up to 30 days post Gram stain result
Time to effective antibiotic therapy	Time to effective antibiotic therapy within 3 days from Gram stain result, defined as treatment with an antibiotic (or antibiotic class) to which the blood isolate is susceptible based on standard of care (SOC) AST.	within 3 days from Gram stain result
Time to antibiotic escalation	Time to antibiotic escalation of Gram negative coverage in those who have antibiotic escalation within 3 days from Gram stain result. Escalation: Changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral (PO) to intravenous (IV) route.	within 3 days from Gram stain result
Time to antibiotic de-escalation of Gram negative coverage	Time to antibiotic de-escalation of Gram negative coverage in those who have antibiotic de-escalation within 3 days from Gram stain result. De-escalation: Changing to a narrower spectrum antibiotic , cessation of one or more antibiotics, or changing from an IV to PO route of appropriate drug (i.e. IV to PO ciprofloxacin or levofloxacin).	within 3 days from Gram stain result
Number of ICU admissions	ICU admission up to 30 days post Gram stain result	up to 30 days post Gram stain result
Number of participants with new Acquisition of Multi-Drug Resistant Organism (MDRO) and/or C. difficile	New acquisition is defined as detection of MDRO/C. difficile in subjects who do not have preceding clinical or surveillance cultures with these organisms in the prior 3 months. MDRO will be identified on routine clinical or surveillance samples using local laboratory diagnostic procedures and include: Methicillin-resistant Staphylococcus aureus Vancomycin-resistant Enterococcus species 3rd generation cephalosporin-non-susceptible Enterobacterales Carbapenem-resistant Enterobacterales, as defined by the Center for Disease Control and Prevention: resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate produces a carbapenemase Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (resistant to aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems) Carbapenem-resistant Acinetobacter species Candida auris	up to 30 days post Gram stain result

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Parexel; BioMérieux
• Investigators: Principal Investigator: Ritu Banerjee, MD, PhD, Vanderbilt University Medical Center; Study Director: Vance Fowler, MD, Duke Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2023
• Primary Completion (Actual): June 18, 2025
• Study Completion (Actual): June 18, 2025

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Bacteremia; Sepsis
• Other Study ID Numbers: Pro00109586; UM1AI104681 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No