Effect of Direct-from-blood Bacterial Testing on Antibiotic Administration and Clinical Outcomes

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06069206

Collaborator

(none)

500

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Bacterial blood stream infections are common and life-threatening. Bloodstream infections have historically been identified using blood cultures, which often take 24-72 hours to result and are imperfectly sensitive (1-5). Early administration of antimicrobial therapy is a fundamental component of the management of adults presenting to the hospital with a suspected bloodstream infection and/or sepsis (6).

But because blood cultures frequently take 24-72 hours to result, patients are typically treated with empiric, broad spectrum antibiotics (7). In a meta-analysis of sepsis studies, empirical antibiotic therapy was inappropriate for the organism that ultimately grew in culture in almost half of patients (6). Thus, patients are commonly exposed to unnecessary antibiotics without evidence of infection or with evidence of infection requiring narrow antibiotic selection. For example, current guidelines recommend the use of empiric intravenous vancomycin as coverage for a bloodstream infection caused by the bacterial pathogen methicillin-resistant S. aureus (MRSA) (8). Vancomycin requires careful monitoring due to its narrow therapeutic range and high risk of toxicity (9). Administration of vancomycin to patients who do not have MRSA can lead to avoidable adverse drug events and costs, as well as drive antimicrobial resistance.

There has been increasing interest in using rapid diagnostic tests that identify bacteria directly from whole blood samples without relying on growth in culture, referred to as "direct-from-blood" tests, to guide early therapeutic management of patients with suspected bloodstream infections in addition to standard blood cultures (10-12). One such FDA-approved, direct-from-blood test is the T2Bacteria® Panel. This panel's performance as a direct-from blood test for bacterial pathogens has been described in previous studies (13-17). A recent meta-analysis of largely observational studies reported a faster transition to targeted microbial therapy and de-escalation of empirical microbial therapy, as well as a shorter duration of intensive care unit stay and hospital stay for patients who received this direct-from-blood test (17).

We will conduct a pragmatic, randomized clinical trial examining the effect of using the T2Bacteria® Panel direct from-blood testing, compared to using blood cultures alone (standard of care), on antimicrobial receipt and clinical outcomes for adults presenting to the hospital with suspected infection and who have been initiated on empiric therapy with intravenous vancomycin.

Condition or Disease	Intervention/Treatment	Phase
Bloodstream Infection Sepsis Bacterial MRSA Bacteremia Vancomycin	Other: Direct-from-blood testing Other: Usual Care	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

Effect of Direct-from-blood Bacterial Testing on Antibiotic Administration and Clinical Outcomes: A Learning Healthcare Pragmatic Randomized Trial

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Usual Care Patients will receive blood cultures and will not receive direct-from-blood testing.	Other: Usual Care Standard blood cultures.
Active Comparator: Direct-from-blood testing In addition to usual care, patients will receive direct-from-blood testing using the T2Bacteria® Panel.	Other: Direct-from-blood testing Providers will be prompted to order the T2Bacteria® Panel (direct-from-blood testing) and accompanying communications regarding panel results will be delivered.

Arm

Intervention/Treatment

Active Comparator: Usual Care

Patients will receive blood cultures and will not receive direct-from-blood testing.

Other: Usual Care

Standard blood cultures.

Active Comparator: Direct-from-blood testing

In addition to usual care, patients will receive direct-from-blood testing using the T2Bacteria® Panel.

Other: Direct-from-blood testing

Providers will be prompted to order the T2Bacteria® Panel (direct-from-blood testing) and accompanying communications regarding panel results will be delivered.

Outcome Measures

Primary Outcome Measures

Time to last dose of intravenous vancomycin [Baseline to 14 days]
The time between randomization and the start time for the last dose of intravenous vancomycin received by the patient within 14 days of randomization.

Secondary Outcome Measures

Time to last dose of systemic anti-pseudomonal beta-lactam antibiotic [Baseline to 14 days]
The time between randomization and start time of the last dose of systemic anti-pseudomonal beta-lactam antibiotic received by the patient within 14 days of randomization.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient is located in the Emergency Department at Vanderbilt University Hospital
≤ 12 hours from patient presentation to the Emergency Department at Vanderbilt University Hospital
Age ≥ 18 years
Clinician has ordered blood cultures
Clinician has ordered intravenous vancomycin

Exclusion Criteria:

Patient is known to be a prisoner
Patient is known to be pregnant
Patient is known to have received more than one dose of intravenous vancomycin within the previous 14 days
Patient is known to have a positive bacterial culture in the previous 7 days
Patient is known to have an infection for which at least 7 days of intravenous vancomycin would routinely be administered regardless of bacterial testing results (e.g., skin and soft tissue infection, etc.)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Vanderbilt University Medical Center

Investigators

Principal Investigator: Matthew Semler, MD, MSc, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Matthew Semler, MD, MSc, Medical Director, Center for Learning Healthcare; Associate Director, Vanderbilt Medical Intensive Care Unit, Vanderbilt University Medical Center

ClinicalTrials.gov Identifier:

NCT06069206

Other Study ID Numbers:

231229

First Posted:

Oct 5, 2023

Last Update Posted:

Oct 5, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Bacteremia

Sepsis

Study Results

No Results Posted as of Oct 5, 2023