Bloodstream Infection, Gram-negative Bacteremia
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTReveal
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).
Sponsors
Duke University
National Institute of Allergy and Infectious Diseases (NIAID)
Parexel
BioMérieux
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Caregiver)
Masking description
Patient and care provider will not know which arm subject is randomized into until after the stewardship team has review the Reveal results and provided feedback on initial therapies prescribed.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Clinical Outcomes, as Measured by Desirability of Outcome Ranking (DOOR) | Up to 30 days after Gram stain result | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-Cause Mortality | Up to 30 days post Gram Stain | All-cause in-hospital mortality up to 30 days post Gram stain result |
| Hospital Stay Length | up to 30 days post Gram stain result | 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. |
| Number of Participants With ICU Admissions | up to 30 days post Gram stain result | ICU admission up to 30 days post Gram stain result |
| Number of Participants With New Acquisition of Multi-Drug Resistant Organism (MDRO) and/or C. Difficile | up to 30 days post Gram stain result | 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 |
| Number of Participants With New Multidrug-Resistant Organism (MDRO) | up to 30 days post Gram stain result | 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 |
| Number of Participants With C. Difficile | up to 30 days post Gram stain result | Detection of C. difficile in subjects who do not have preceding clinical or surveillance cultures with these organisms in the prior 3 months. |
| Number of Participants With MRSA | up to 30 days post Gram stain result | Detection of Methicillin-resistant Staphylococcus aureus (MRSA) |
| Number of Participants With VRE | up to 30 days post Gram stain result | Detection of Vancomycin-resistant Enterococcus species (VRE) |
| Number of Participants With CTX Resistant Enterobacterales | up to 30 days post Gram stain result | Detection of 3rd generation cephalosporin-non-susceptible Enterobacterales (CTX resistant Enterobacterales) |
| Number of Participants With CRE | up to 30 days post Gram stain result | Detection of Carbapenem-resistant Enterobacterales (CRE) |
| Number of Participants With MDR Pseudomonas | up to 30 days post Gram stain result | Detection of Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (MDR Pseudomonas) |
| Number of Participants With CRAb | up to 30 days post Gram stain result | Detection of Carbapenem-resistant Acinetobacter species (CRAb) |
| Number of Participants With Candida Auris | up to 30 days post Gram stain result | Detection of Candida auris using local laboratory diagnostic precedures |
| Time to Effective Antibiotic Therapy | within 3 days from Gram stain result | 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. |
| Receiving Effective Antibiotic Therapy Within 24 Hours | within 24 hours from Gram stain result | 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. |
| Receiving Effective Antibiotic Therapy Within 3 Days | within 3 days from Gram stain result | 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 to Antibiotic Escalation or De-escalation | within 3 days from Gram stain result | 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). |
| Antibiotic Change Within 3 Days | within 3 days from Gram stain result | 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. |
Countries
Greece, India, Israel, Spain
Contacts
PRINCIPAL_INVESTIGATORRitu Banerjee, MD, PhD
Vanderbilt University Medical Center
STUDY_DIRECTORVance Fowler, MD
Duke Clinical Research Institute
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 72 Years |
| Age, Customized 0-18 | 10 Participants |
| Age, Customized 19-39 | 48 Participants |
| Age, Customized 40-59 | 147 Participants |
| Age, Customized 60-69 | 155 Participants |
| Age, Customized 70-79 | 252 Participants |
| Age, Customized 80+ | 238 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 785 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian/Not Hispanic or Latino | 46 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian/Unknown Ethnicity | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black/Not Hispanic or Latino | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other or multiple Race/Not Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White/Hispanic or Latino | 31 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White/Not Hispanic or Latino | 682 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White/Unknown Ethnicity | 3 Participants |
| Region of Enrollment Greece | 210 Participants |
| Region of Enrollment India | 48 Participants |
| Region of Enrollment Israel | 291 Participants |
| Region of Enrollment Spain | 31 Participants |
| Sex: Female, Male Female | 189 Participants |
| Sex: Female, Male Male | 486 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 100 / 413 | 99 / 437 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
None listed