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CompletedNCT03255759Updated Mar 10, 2021

Actionable Results: Bloodstream Infection Molecular Assay Evaluation

An interventional study of Multiplex molecular diagnostic assay in Bloodstream Infection, sponsored by Foundation for Innovative New Diagnostics, Switzerland. Completed at 1 site in Botswana. Per ClinicalTrials.gov, last updated 2021-03-10.

Sponsored by Foundation for Innovative New Diagnostics, Switzerland · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
312
Allocation
Randomized
Sex
All
01

Study summary

A number of rapid panel-based molecular assays for direct organism identification and resistance characterization in positive blood culture bottles are now commercially available. They have been shown to improve accuracy and decrease the time-to-result, allowing targeted treatment in hospitalized patients with bacteraemia, in high-income countries (HICs). However, these molecular assays are add-on tests performed in addition to conventional testing, increasing the complexity of diagnostic algorithms and costs of patient care. Conventional organism identification includes performing a Gram stain, biochemical identification and phenotypic drug susceptibility testing. The FilmArray Blood Culture Identification (BioFire, USA) is an example of a rapid panel-based molecular assay that combines nesting and multiplexing of PCR (nested multiplex PCR) to detect multiple pathogens simultaneously. There are limited data on how such tests impact patient management, health care costs and how they can better be incorporated into diagnostic algorithms.

The aim of this study is to assess the added value and acceptability of a multiplexed molecular diagnostic assay in the identification of pathogens in patients presenting with bacteremia at hospitals in LMICs, and to assess health care providers' satisfaction with the assay.

Read the detailed description

The study will address the following questions:

  1. What impact can we project if additional diagnostic information were to be provided to clinicians in terms of patient outcomes, costs, and antibiotic use?
  2. What are the workflow constraints on returning diagnostic results to clinicians and/or antibiotic stewardship programs? Overall, the aim is to assess the added value and acceptability of a multiplexed molecular diagnostic assay in the identification of pathogens in patients presenting with bacteremia at hospitals in LMICs and to assess health care providers' satisfaction with the assay.
02

Conditions studied

  • Bloodstream Infection
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • For patients of Princess Marina Hospital: all participants who have a blood culture done as part of routine clinical care that is found to be positive through routine laboratory testing from Monday-Friday 8am-3pm (excluding holidays) will be eligible for inclusion in the study, regardless of age and co-morbidities.
  • For the professionals making use of molecular testing: Attending physicians (paediatricians, internists, and physician trainees [residents, medical officers, interns]) caring for adults and children who are enrolled in the study, Microbiologists and microbiology technologists who have experience operating the BioFire FilmArray and/or traditional blood culture incubation systems at the laboratory.

Exclusion criteria

Exclusion Criteria:

  • For patients of Princess Marina Hospital: Individuals who have previously participated in the study by having a blood culture positive in the week prior will not be eligible to participate again within the 7-day time frame.
  • For professionals making use of molecular testing: Individuals working with patients or laboratory samples at Princess Marina Hospital for less than one month will not be asked to participate.
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
312 participants (actual)

Study arms

  • Active comparator
    Molecular dx arm

    Positive blood cultures are tested using a molecular ID system in addition to the standard of care (biochemical identification)

    Diagnostic Test: Multiplex molecular diagnostic assay

  • No intervention
    Standard of care arm

    Positive blood cultures are treated as per normal lab protocol (biochemical identification)

Interventions

  • Diagnostic testMultiplex molecular diagnostic assay

    To assess the added value and acceptability of a multiplexed molecular diagnostic assay in the identification of pathogens in patients presenting with bacteremia at hospitals in LMICs, and to assess health care providers' satisfaction with the assay.

05

What researchers measure

Primary outcomes

  1. Time from blood collection to definitive treatment initiation (optimal treatment defined as time from blood culture collection to the initiation of a predetermined pathogen-specific antimicrobial therapy)

    The judgment as to whether antimicrobial treatment was effective or optimal will be assessed by two members of the study team (infectious disease specialists and/or microbiologists) blinded to treatment group. A third, blinded, party member will be available to adjudicate unresolved disagreements. The Principal Investigators will not be involved in outcome classification.

    Time frame: 1year

Secondary outcomes

  1. Time from blood collection to initiation of effective antimicrobial therapy (initiation of antimicrobials active against the identified causative pathogen)

    The aim is to understand the reduction in time it takes clinical staff to act upon the result. Faster treatment is associated with reduced mortality.

    Time frame: 1year

  2. Time from blood collection to pathogen identification

    The hypothesis is that faster identification will lead to faster action.

    Time frame: 1year

  3. Proportion of patients with a confirmed diagnosis of bloodstream infection who are started on optimal antimicrobial therapy in the intervention compared to control arm.

    This outcome will inform how the inclusion of a faster diagnosis can support antibiotic stewardship efforts.

    Time frame: 1year

  4. Frequency of discrepant results between molecular identification vs standard of care.

    Current panels are design for common pathogens in the USA and Europe and given that this is the first evaluation in Africa it will advice on the suitability.

    Time frame: 1year

  5. Clinicians' satisfaction with the assay, predominantly in terms of time-to-result and actionable results.

    To inform future projects and help guide implementation efforts.

    Time frame: 2month

  6. Laboratory professional satisfaction with the assay, predominantly in terms of ease of use and workflow.

    To inform future projects and help guide implementation efforts.

    Time frame: 2month

  7. In-hospital mortality.

    Faster treatment is associated with reduced mortaltity and as a secondary outcome we want to assess the difference between standard of care and diagnostic intervention.

    Time frame: 1year

  8. 30-day mortality.

    Faster treatment is associated with reduced mortaltity and as a secondary outcome we want to assess the difference between standard of care and diagnostic intervention.

    Time frame: 1year

06

Study locations

1 site
  • Princess Marina Hospital
    Gaborone, Botswana
07

Registry details

Key details

Study ID
NCT03255759
Lead sponsor
Foundation for Innovative New Diagnostics, Switzerland
Responsible party
Sponsor
First posted
Aug 21, 2017
Start date
May 24, 2018
Primary completion
Mar 31, 2020
Completion
Mar 31, 2020
Last update
Mar 10, 2021

Study contacts

Jeffrey Pernica, MD, FRCPC
principal investigator · McMaster University
David Goldfarb, MD, FRCPC
principal investigator · University of British Columbia

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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