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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
DOUBLE
Enrollment
899
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).
Attikon University General Hospital
Chaïdári, Attica, Greece
Tzaneio General Hospital
Piraeus, Greece
Kasturba Medical College, Mangalore
Attāvara, Mangalore, India
Rambam Health Care Campus
Haifa, Israel
Meir Medical Center
Kfar Saba, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Complexo Hospitalario Universitario A Coruña (CHUAC) Sergas
A Coruña, Spain
Participant 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: 1. Alive without deleterious events 2. Alive with at least 1 deleterious event 3. Death
Time frame: Up to 30 days after Gram stain result
Number of Participants With All-Cause Mortality
All-cause in-hospital mortality up to 30 days post Gram stain result
Time frame: 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.
Time frame: up to 30 days post Gram stain result
Number of Participants With ICU Admissions
ICU admission up to 30 days post Gram stain result
Time frame: 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
Time frame: up to 30 days post Gram stain result
Number of Participants With New Multidrug-Resistant Organism (MDRO)
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
Time frame: up to 30 days post Gram stain result
Number of Participants With C. Difficile
Detection of C. difficile in subjects who do not have preceding clinical or surveillance cultures with these organisms in the prior 3 months.
Time frame: up to 30 days post Gram stain result
Number of Participants With MRSA
Detection of Methicillin-resistant Staphylococcus aureus (MRSA)
Time frame: up to 30 days post Gram stain result
Number of Participants With VRE
Detection of Vancomycin-resistant Enterococcus species (VRE)
Time frame: up to 30 days post Gram stain result
Number of Participants With CTX Resistant Enterobacterales
Detection of 3rd generation cephalosporin-non-susceptible Enterobacterales (CTX resistant Enterobacterales)
Time frame: up to 30 days post Gram stain result
Number of Participants With CRE
Detection of Carbapenem-resistant Enterobacterales (CRE)
Time frame: up to 30 days post Gram stain result
Number of Participants With MDR Pseudomonas
Detection of Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (MDR Pseudomonas)
Time frame: up to 30 days post Gram stain result
Number of Participants With CRAb
Detection of Carbapenem-resistant Acinetobacter species (CRAb)
Time frame: up to 30 days post Gram stain result
Number of Participants With Candida Auris
Detection of Candida auris using local laboratory diagnostic precedures
Time frame: 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.
Time frame: within 3 days from Gram stain result
Receiving Effective Antibiotic Therapy Within 24 Hours
Effective antibiotic therapy was defined as treatment with an antibiotic (or antibiotic class) to which the blood isolate is susceptible based on standard of care (SOC) AST and to which the isolate was not intrinsically resistant.
Time frame: within 24 hours from Gram stain result
Receiving Effective Antibiotic Therapy Within 3 Days
Effective antibiotic therapy was defined as treatment with an antibiotic (or antibiotic class) to which the blood isolate is susceptible based on standard of care (SOC) AST and to which the isolate was not intrinsically resistant.
Time frame: within 3 days from Gram stain result
Time to Antibiotic Escalation or De-escalation
Time to antibiotic escalation or de-escalation of Gram negative coverage in those who have antibiotic change 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. 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).
Time frame: within 3 days from Gram stain result
Antibiotic Change Within 3 Days
Antibiotic changes for Gram-negative coverage within 3 days from Gram stain result. Among as-randomized population, the antibiotic utilization can be categorized as follow: (a) first change is escalation, (b) first change is de-escalation, (c) no change, and (d) no Gram-negative antibiotic received within 3 days.
Time frame: within 3 days from Gram stain result
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