Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial

Duke University900 enrolled

Overview

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

900

Conditions

Gram-negative Bacteremia Bloodstream Infection

Interventions

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).

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Locations (7)

Attikon University General Hospital

Chaïdári, Attica, Greece

Tzaneio General Hospital

Piraeus, Greece

Kasturba Medical College, Mangalore

Attavāra, 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

Outcomes

Primary Outcomes

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: 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

Secondary Outcomes

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 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

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

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.

Time frame: 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).

Time frame: within 3 days from Gram stain result