Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial

Study Overview
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Brief Summary
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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.

Official Title
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Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial

Conditions
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Gram-negative Bacteremia, Bloodstream Infection

Intervention / Treatment
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* Diagnostic Test: Reveal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive blood culture with Gram stain showing GNB Hospitalized at the time of Gram stain result Exclusion Criteria: Positive blood culture for GNB at the same institution within the prior 7 days (if known at the time of Gram stain result) Deceased at the time of Gram stain result Gram-positive bacilli, Gram-positive cocci, Gram-negative cocci, yeast, fungi, or multiple morphologies of GNB detected on Gram stain of blood culture Previous enrollment in this study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>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<br>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<br>* 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).<br>|

What is the study measuring?
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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 | 
| 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 | 
| 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 |