Rapid Identification and Phenotypic Susceptibility Testing for Gram-Negative Bacteremia (RAPIDS-GN)

Rapid Identification and Phenotypic Susceptibility Testing for Gram-Negative Bacteremia (RAPIDS-GN)

RAPIDS-GN is a multi-center, prospective, randomized, controlled trial to evaluate the following strategies for patients with confirmed gram-negative bacillus bacteremia (GNB):

1. Standard culture and antimicrobial susceptibility testing (AST); or
2. Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)

Study Overview

• Status: Completed
• Conditions: Gram-negative Bacteremia
• Intervention / Treatment: Device: Standard Culture and AST; Device: Accelerate PhenoTest™ BC Kit

Detailed Description

RAPIDS-GN is a multi-center, prospective, randomized, controlled trial to evaluate the following strategies for patients with confirmed gram-negative bacillus bacteremia (GNB):

1. Standard culture and antimicrobial susceptibility testing (AST); or
2. Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)

Patient specimens with positive blood culture with Gram stain showing GNB identified during local laboratory business hours will be enrolled by the Microbiology Laboratory Technologist if they do not meet any exclusion criteria. Subject specimens will be randomized 1:1 to standard culture and AST or Rapid identification and AST using the FDA approved Accelerate Pheno TM System. Both groups will receive standard antimicrobial stewardship (AS). The primary service, including the prescribing provider, will be unaware of group assignment at the time of randomization, so initial antibiotic choice will not be affected by group assignment. Once rapid results become available and/or AS interventions are made, treating providers may become aware of group assignment.

The goal of this study is to determine the impact of rapid bacterial identification and phenotypic antimicrobial susceptibility testing (AST) on antimicrobial usage and clinical outcomes.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90049
      • University of California, Los Angeles
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Positive blood culture with Gram stain showing GNB identified during local laboratory business hours.

Exclusion Criteria:

• Identification of GNB outside of local laboratory business hours (e.g. whenever laboratories are staffed to perform both rapid testing and routine testing)
• Positive blood culture for GNB at the same institution within prior 7 days (if known at the time of randomization).
• Deceased at the time of randomization.
• GNB plus gram-positive organism, gram-negative cocci, and/or yeast detected on Gram stain
• Previous enrollment in this study
• No Minnesota research authorization (Rochester site only)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard blood culture and AST; Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Device: Standard Culture and AST; Standard culture and antimicrobial susceptibility testing (AST)
Active Comparator: Rapid organism identification and AST; Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.	Device: Accelerate PhenoTest™ BC Kit; Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hours to First Antibiotic Modification	Mean hours until first modification of antibiotic therapy within 72 hours post randomization	72 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects Who Experienced Mortality Within 30 Days of Randomization	Subjects who experienced mortality within 30 days of randomization	Within 30 days of randomization
Length of Stay in the Hospital	Length of stay in the hospital after randomization, up to 30 days, for patients alive at 30 days. Length of stay will be date of discharge minus date of randomization.	Within 30 days of randomization
ICU Status Through 72 Hours Post-randomization	ICU status through 72 hours post-randomization	Within 72 hours of randomization
Time to First Antibiotic Escalation	Mean hours to first antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route.	Within 72 hours of randomization
Time to First Gram-negative Antibiotic Escalation	Mean hours to first gram-negative antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route.	Within 72 hours of randomization
Time to First Gram-positive Antibiotic Escalation	Mean hours to first gram-positive antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route.	Within 72 hours of randomization
Time to First Antibiotic De-escalation	Mean hours to first antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug.	Within 72 hours of randomization
Time to First Gram-negative Antibiotic De-escalation	Mean hours to first gram-negative antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug.	Within 72 hours of randomization
Time to First Gram-positive Antibiotic De-escalation	Mean hours to first gram-positive antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug.	Within 72 hours of randomization
Number of Hospital-onset Clostridium Difficile Infections	Acquisition of hospital-onset Clostridium difficile within 30 days, as defined by the National Healthcare Safety Network (NHSN), normalized to 10,000 patient-days.	Within 30 days of randomization
Number of New Hospital-acquired Infections (HAIs) and/or Multidrug Resistant Organisms (MDROs), Normalized to 10,000 Patient-days.	Acquisition of new hospital-acquired infections (HAIs) and/or multidrug resistant organisms (MDROs) within 30 days during index hospitalization identified on routine clinical or surveillance samples. Cultures that will be tracked include the following, from any specimen source, unless otherwise indicated: Methicillin-resistant Staphylococcus aureus; Vancomycin-resistant Enterococcus; 3rd generation cephalosporin non-susceptible Enterobacteriaceae; Carbapenem-resistant Enterobacteriaceae, as defined by the Centers for Disease Control and Prevention (CDC): resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate possesses a carbapenemase; Multidrug-resistant Pseudomonas aeruginosa (resistant to aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems); Carbapenem-resistant Acinetobacter; Candida species (isolated from blood cultures only)	Within 30 days of randomization

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Vanderbilt University
• Investigators: Study Chair: Ritu Banerjee, MD, PhD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Banerjee R, Komarow L, Virk A, Rajapakse N, Schuetz AN, Dylla B, Earley M, Lok J, Kohner P, Ihde S, Cole N, Hines L, Reed K, Garner OB, Chandrasekaran S, de St Maurice A, Kanatani M, Curello J, Arias R, Swearingen W, Doernberg SB, Patel R. Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN. Clin Infect Dis. 2021 Jul 1;73(1):e39-e46. doi: 10.1093/cid/ciaa528.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Actual): November 3, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): November 26, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: ICU; Intensive Care Unit; Antimicrobial stewardship; Critically ill; Gram-negative Bacteremia; Rapid identification; Rapid susceptibility; Accelerate PhenoTest™ BC Kit; Accelerate Pheno™ System (AXDX); Antimicrobial use
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia; Disease Susceptibility
• Other Study ID Numbers: Pro00075768; 5UM1AI104681 (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: Yes