<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03255759</url>
  </required_header>
  <id_info>
    <org_study_id>08821/1/1</org_study_id>
    <nct_id>NCT03255759</nct_id>
  </id_info>
  <brief_title>Actionable Results: Bloodstream Infection Molecular Assay Evaluation</brief_title>
  <official_title>Assessment of the Use and Impact of a Molecular Identification Assay in the Diagnosis and Management of Bloodstream Infections at in Healthcare Settings in Princess Marina Hospital, Botswana</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Foundation for Innovative New Diagnostics, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Foundation for Innovative New Diagnostics, Switzerland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A number of rapid panel-based molecular assays for direct organism identification and&#xD;
      resistance characterization in positive blood culture bottles are now commercially available.&#xD;
      They have been shown to improve accuracy and decrease the time-to-result, allowing targeted&#xD;
      treatment in hospitalized patients with bacteraemia, in high-income countries (HICs).&#xD;
      However, these molecular assays are add-on tests performed in addition to conventional&#xD;
      testing, increasing the complexity of diagnostic algorithms and costs of patient care.&#xD;
      Conventional organism identification includes performing a Gram stain, biochemical&#xD;
      identification and phenotypic drug susceptibility testing. The FilmArray Blood Culture&#xD;
      Identification (BioFire, USA) is an example of a rapid panel-based molecular assay that&#xD;
      combines nesting and multiplexing of PCR (nested multiplex PCR) to detect multiple pathogens&#xD;
      simultaneously. There are limited data on how such tests impact patient management, health&#xD;
      care costs and how they can better be incorporated into diagnostic algorithms.&#xD;
&#xD;
      The aim of this study is to assess the added value and acceptability of a multiplexed&#xD;
      molecular diagnostic assay in the identification of pathogens in patients presenting with&#xD;
      bacteremia at hospitals in LMICs, and to assess health care providers' satisfaction with the&#xD;
      assay.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will address the following questions:&#xD;
&#xD;
        1. What impact can we project if additional diagnostic information were to be provided to&#xD;
           clinicians in terms of patient outcomes, costs, and antibiotic use?&#xD;
&#xD;
        2. What are the workflow constraints on returning diagnostic results to clinicians and/or&#xD;
           antibiotic stewardship programs? Overall, the aim is to assess the added value and&#xD;
           acceptability of a multiplexed molecular diagnostic assay in the identification of&#xD;
           pathogens in patients presenting with bacteremia at hospitals in LMICs and to assess&#xD;
           health care providers' satisfaction with the assay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 24, 2018</start_date>
  <completion_date type="Actual">March 31, 2020</completion_date>
  <primary_completion_date type="Actual">March 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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)</measure>
    <time_frame>1year</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from blood collection to initiation of effective antimicrobial therapy (initiation of antimicrobials active against the identified causative pathogen)</measure>
    <time_frame>1year</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from blood collection to pathogen identification</measure>
    <time_frame>1year</time_frame>
    <description>The hypothesis is that faster identification will lead to faster action.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with a confirmed diagnosis of bloodstream infection who are started on optimal antimicrobial therapy in the intervention compared to control arm.</measure>
    <time_frame>1year</time_frame>
    <description>This outcome will inform how the inclusion of a faster diagnosis can support antibiotic stewardship efforts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of discrepant results between molecular identification vs standard of care.</measure>
    <time_frame>1year</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinicians' satisfaction with the assay, predominantly in terms of time-to-result and actionable results.</measure>
    <time_frame>2month</time_frame>
    <description>To inform future projects and help guide implementation efforts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory professional satisfaction with the assay, predominantly in terms of ease of use and workflow.</measure>
    <time_frame>2month</time_frame>
    <description>To inform future projects and help guide implementation efforts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality.</measure>
    <time_frame>1year</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day mortality.</measure>
    <time_frame>1year</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">312</enrollment>
  <condition>Bloodstream Infection</condition>
  <arm_group>
    <arm_group_label>Molecular dx arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Positive blood cultures are tested using a molecular ID system in addition to the standard of care (biochemical identification)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Positive blood cultures are treated as per normal lab protocol (biochemical identification)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Multiplex molecular diagnostic assay</intervention_name>
    <description>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.</description>
    <arm_group_label>Molecular dx arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For patients of Princess Marina Hospital: all participants who have a blood culture&#xD;
             done as part of routine clinical care that is found to be positive through routine&#xD;
             laboratory testing from Monday-Friday 8am-3pm (excluding holidays) will be eligible&#xD;
             for inclusion in the study, regardless of age and co-morbidities.&#xD;
&#xD;
          -  For the professionals making use of molecular testing: Attending physicians&#xD;
             (paediatricians, internists, and physician trainees [residents, medical officers,&#xD;
             interns]) caring for adults and children who are enrolled in the study,&#xD;
             Microbiologists and microbiology technologists who have experience operating the&#xD;
             BioFire FilmArray and/or traditional blood culture incubation systems at the&#xD;
             laboratory.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For patients of Princess Marina Hospital: Individuals who have previously participated&#xD;
             in the study by having a blood culture positive in the week prior will not be eligible&#xD;
             to participate again within the 7-day time frame.&#xD;
&#xD;
          -  For professionals making use of molecular testing: Individuals working with patients&#xD;
             or laboratory samples at Princess Marina Hospital for less than one month will not be&#xD;
             asked to participate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey Pernica, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Goldfarb, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Princess Marina Hospital</name>
      <address>
        <city>Gaborone</city>
        <country>Botswana</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Botswana</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>March 9, 2021</last_update_submitted>
  <last_update_submitted_qc>March 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Sepsis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03255759
org study id: 08821/1/1
nct id: NCT03255759
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: 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)
time frame: 1year
description: 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.
measure: Time from blood collection to initiation of effective antimicrobial therapy (initiation of antimicrobials active against the identified causative pathogen)
time frame: 1year
description: 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.
measure: Time from blood collection to pathogen identification
time frame: 1year
description: The hypothesis is that faster identification will lead to faster action.
measure: Proportion of patients with a confirmed diagnosis of bloodstream infection who are started on optimal antimicrobial therapy in the intervention compared to control arm.
time frame: 1year
description: This outcome will inform how the inclusion of a faster diagnosis can support antibiotic stewardship efforts.
measure: Frequency of discrepant results between molecular identification vs standard of care.
time frame: 1year
description: 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.
measure: Clinicians' satisfaction with the assay, predominantly in terms of time-to-result and actionable results.
time frame: 2month
description: To inform future projects and help guide implementation efforts.
measure: Laboratory professional satisfaction with the assay, predominantly in terms of ease of use and workflow.
time frame: 2month
description: To inform future projects and help guide implementation efforts.
measure: In-hospital mortality.
time frame: 1year
description: 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.
measure: 30-day mortality.
time frame: 1year
description: 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.
arm group label: Molecular dx arm
arm group type: Active Comparator
description: Positive blood cultures are tested using a molecular ID system in addition to the standard of care (biochemical identification)
arm group label: Standard of care arm
arm group type: No Intervention
description: Positive blood cultures are treated as per normal lab protocol (biochemical identification)
intervention type: Diagnostic Test
intervention name: Multiplex molecular diagnostic assay
description: 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.
arm group label: Molecular dx arm
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jeffrey Pernica, MD, FRCPC
role: Principal Investigator
affiliation: McMaster University
last name: David Goldfarb, MD, FRCPC
role: Principal Investigator
affiliation: University of British Columbia
facility: 
country: Botswana
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Sepsis