xml: <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/NCT05989269</url>
    </required_header>
    <id_info>
      <org_study_id>HP-00100090</org_study_id>
      <nct_id>NCT05989269</nct_id>
    </id_info>
    <brief_title>Diagnostic Stewardship for Ventilator Associated Pneumonia</brief_title>
    <official_title>Diagnostic Stewardship for Ventilator Associated Pneumonia: A Pragmatic Cluster-randomized Crossover Trial of a Hybrid Order-review and Laboratory Reporting Intervention</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Maryland, Baltimore</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Centers for Disease Control and Prevention</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
      <collaborator>
        <agency>George Washington University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Baylor College of Medicine</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Virginia Commonwealth University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Maryland, Baltimore</source>
    <oversight_info>
      <has_dmc>No</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>
        The goal of this pragmatic cluster-randomized crossover trial is to test if less unnecessary&#xD;
        antibiotics are prescribed when the lab reports respiratory culture test results in a&#xD;
        specific way for patients who have respiratory cultures obtained, but do not meet clinical&#xD;
        criteria for ventilator associated pneumonia (VAP). The main question it aims to answer is:&#xD;
        Does a modified culture reporting intervention reduce unnecessary antibiotics for ventilated&#xD;
        patients in the intensive care unit (ICU)? Researchers will compare antibiotic use outcomes&#xD;
        between eligible patients whose test results are communicated using the modified reporting&#xD;
        and those with standard reporting of results.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The specific aims of this project are:&#xD;
  &#xD;
        Specific Aim 1: In a cluster-randomized crossover trial among 6 ICUs across 3 medical&#xD;
        centers, evaluate the impact of a VAP diagnostic stewardship intervention on antibiotic use,&#xD;
        VAP diagnoses, and adverse events.&#xD;
  &#xD;
        Hypothesis: A change in unnecessary antibiotics for VAP and in VAP clinical diagnoses in the&#xD;
        intervention vs. control periods across all sites, without a change in adverse events, is&#xD;
        expected.&#xD;
  &#xD;
        Specific Aim 2: Evaluate overall impact of intervention including clinical and antibiotic&#xD;
        outcomes using the &quot;Desirability of Outcome Ranking (DOOR)/ Response Adjusted for Duration of&#xD;
        Antibiotic Risk (RADAR)&quot; methodology.&#xD;
  &#xD;
        Hypothesis: A change in overall patient outcomes (better DOOR ranking, accounting for&#xD;
        duration of antibiotic use) in the intervention vs. control period is expected.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 14, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 14, 2024</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>Crossover Assignment</intervention_model>
      <intervention_model_description>This is a pragmatic cluster-randomized crossover trial in 6 adult ICUs (1 medical and 1 surgical ICU each at 3 hospitals). ICUs (clusters) will be randomized at the hospital-level (1:1) to a sequence of intervention (6 months) followed by control (6 months), or vice-versa. The study population is ventilated patients with respiratory culture orders but not meeting clinical pneumonia criteria, and organism(s) growing in respiratory culture. A research physician will evaluate likelihood of pneumonia using a standard clinical algorithm, within 24 hours of the order Mon-Fri. If pneumonia criteria are not met AND there is growth of organism(s) (except normal respiratory flora), during the intervention period, the culture report will be modified to reflect the likelihood of asymptomatic colonization instead of reporting bacterial identification. Clinicians may call the lab for identification and susceptibilities if necessary. During the control period, no modification to reporting will occur.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>Single (Care Provider)</masking>
      <masking_description>Ordering care providers will not be aware if the test results are eligible for modified reporting or not.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Proportion of unnecessary antibiotic therapy</measure>
      <time_frame>Respiratory culture collection date through day 28 or patient discharge</time_frame>
      <description>The primary efficacy outcome is change in proportion of unnecessary antibiotic therapy for presumed VAP in the intervention (modified reporting) period compared to control (standard reporting) period.&#xD;
  Antibiotic use for VAP relative to the index respiratory culture will be classified as follows:&#xD;
  Not on empiric antibiotic(s), new antibiotic started based on index respiratory culture result&#xD;
  Not on empiric antibiotic(s), no new antibiotics initiated based on culture result&#xD;
  On empiric antibiotic(s), changed based on index respiratory culture, completed course for VAP&#xD;
  On empiric antibiotic(s), continued without change following index respiratory culture, completed course for VAP&#xD;
  On empiric antibiotic(s), antibiotics discontinued based on culture results&#xD;
  On empiric antibiotics(s), but this was not directed towards VAP Antibiotic use in categories a, c, and d will together be considered &quot;unnecessary antibiotic therapy for VAP treatment&quot;.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Antibiotic consumption</measure>
      <time_frame>Measured over the 6 month control period and the 6 month intervention period</time_frame>
      <description>To understand the impact on antibiotic use in ICU patients, we will measure the duration of antibiotic therapy for study patients, unit-level total antibiotic days of therapy (DOTs) standardized to patient census, and unit-level respiratory antibiotic days of therapy (DOTs) standardized to patient census.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of clinical diagnosis of VAP and tracheobronchitis</measure>
      <time_frame>Measured within the 7 days after the index respiratory culture</time_frame>
      <description>Measurement of this outcome will help understand how modification of reporting would influence the likelihood of a patient receiving a diagnosis of VAP. The clinical diagnosis of VAP is an intermediate outcome that precedes the endpoint of antibiotic use. Because there are no consensus definitions for VAP, we will use the treating clinician's documentation of pneumonia or VAP and treatment for those conditions to capture this outcome. Similarly, clinical diagnosis of tracheobronchitis within 7 days after the index culture will also be recorded.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Antibiotic use outcome sensitivity analysis</measure>
      <time_frame>Measured within the 7 days after the index respiratory culture</time_frame>
      <description>We will perform a sensitivity analysis of the impact on antibiotic use outcomes after excluding patients diagnosed with tracheobronchitis within 7 days of index culture. The hypothesis is that the intervention will have limited impact on those diagnosed and treated for tracheobronchitis, and thus, we may see a larger difference between intervention and control when excluding patients with diagnoses of tracheobronchitis.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Ventilator-free days</measure>
      <time_frame>Measured within the 28 days after the index respiratory culture</time_frame>
      <description>Ventilator-free days is defined as the number of calendar days within 28 days after the index respiratory culture on which the patient was not mechanically ventilated. Any patient dying within 28 days of the index respiratory culture collection will be assigned zero ventilator-free days. Ventilator-free days will be compared between the intervention and control periods for all study ICUs combined, and by hospital.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of provider requests for complete reports</measure>
      <time_frame>Measured during the 6 month intervention period</time_frame>
      <description>Frequency of requests for complete reports in the intervention period - these data are applicable in the intervention period only. This will be a primarily descriptive analysis to help us understand if the intervention worked as intended i.e., how frequently did clinicians still want the full report with organism identification despite the nudge to consider asymptomatic colonization.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Adverse Events</measure>
      <time_frame>Measured within the 7 days after the index respiratory culture</time_frame>
      <description>Death, bacteremia, and septic shock (from any cause) within 7 days of the index culture order will be recorded as potential significant adverse events from a delayed or missed true VAP diagnosis or delay in initiation of appropriate antimicrobial therapy. Two-person adjudication will be used to determine whether the above events were attributed to the intervention, during the intervention period. Rates of these events will be compared between intervention and control periods individually for each event, and as a combined adverse event outcome.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Desirability of Outcome Ranking (DOOR)/Response Adjusted for Duration of Antibiotic Risk (RADAR)</measure>
      <time_frame>Measured within the 28 days after the index respiratory culture</time_frame>
      <description>The clinical outcome of a participant will be ranked from most to least desirable outcome, to obtain a 5-level ordinal outcome. We will conduct a series of pairwise comparisons of each intervention patient to each control patient using two rules: When comparing patients with different overall clinical outcomes, the patient with a better overall clinical outcome based on pre-specified ordered ranks is determined to have the better outcome. When comparing two patients who have the same rank based on overall clinical outcome, the patient with a shorter course of antibiotics has the better outcome. The DOOR/RADAR probability represents the probability that a randomly selected participant who received the intervention (modified reporting) has a better overall outcome than a randomly selected participant who received standard reporting (control), accounting for antibiotic duration of therapy.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">400</enrollment>
    <condition>Ventilator Associated Pneumonia</condition>
    <arm_group>
      <arm_group_label>Control Period</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Laboratory reporting of respiratory cultures will continue per regular or routine laboratory protocols (standard reporting).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intervention</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>The lab will publish a modified report for respiratory cultures which do not meet clinical criteria for pneumonia and have growth of organisms (other than normal respiratory flora). The modified report will include the likelihood of colonization instead of reporting bacterial identification.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Modified lab reporting</intervention_name>
      <description>If appropriateness of culturing i.e., clinical criteria for pneumonia testing does not meet the algorithm AND there is growth of one or more organism(s) that are not considered normal upper respiratory flora, during the intervention period, the result will be modified to reflect the likelihood of asymptomatic colonization.</description>
      <arm_group_label>Intervention</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patient located on ICU unit included in the study&#xD;
  &#xD;
            -  Patient is mechanically ventilated&#xD;
  &#xD;
            -  Patient had respiratory culture sent &gt;48 hours after admission&#xD;
  &#xD;
            -  Patient age ≥ 18 years&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Extra corporeal membrane oxygenation (ECMO) at time of respiratory culture&#xD;
  &#xD;
            -  Heart or lung transplant&#xD;
  &#xD;
            -  Culture rejected by lab per standard lab protocol&#xD;
  &#xD;
            -  Prisoners&#xD;
  &#xD;
            -  Severe immunosuppression as defined by:&#xD;
  &#xD;
            -  &lt;6 months from solid organ transplant (SOT) OR &lt;6 months from treatment for acute&#xD;
               rejection following SOT&#xD;
  &#xD;
            -  Active treatment for lymphoreticular malignancies&#xD;
  &#xD;
            -  Neutropenic &lt; 1000&#xD;
  &#xD;
            -  Receiving lymphodepleting chemotherapy&#xD;
  &#xD;
            -  Allogeneic stem cell transplants &lt;6 months&#xD;
  &#xD;
            -  Autologous stem cell transplants or chimeric antigen receptor T-cell (CAR-T) therapy&#xD;
               &lt;6 months out&#xD;
  &#xD;
            -  Allogeneic stem cell transplant with graft vs host disease (GVHD) or receiving 2 or&#xD;
               more immunosuppressants&#xD;
  &#xD;
            -  Advanced or untreated human immunodeficiency virus (HIV) infection with CD4 &lt; 200&#xD;
  &#xD;
            -  Receiving biologics within 6 months&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Michelle Newman, BSN</last_name>
      <phone>4107060933</phone>
      <email>mnewman@som.umaryland.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Surbhi Leekha, MD</last_name>
      <phone>4107066125</phone>
      <email>sleekha@som.umaryland.edu</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
      <investigator_full_name>Surbhi Leekha</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pneumonia</mesh_term>
      <mesh_term>Pneumonia, Ventilator-Associated</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Statistical Analysis Plan</document_type>
        <document_has_protocol>No</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>Yes</document_has_sap>
        <document_date>August 11, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT05989269/SAP_001.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05989269
  org study id: HP-00100090
  nct id: NCT05989269
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this pragmatic cluster-randomized crossover trial is to test if less unnecessary
        antibiotics are prescribed when the lab reports respiratory culture test results in a
        specific way for patients who have respiratory cultures obtained, but do not meet clinical
        criteria for ventilator associated pneumonia (VAP). The main question it aims to answer is:
        Does a modified culture reporting intervention reduce unnecessary antibiotics for ventilated
        patients in the intensive care unit (ICU)? Researchers will compare antibiotic use outcomes
        between eligible patients whose test results are communicated using the modified reporting
        and those with standard reporting of results.
  The specific aims of this project are:
  
        Specific Aim 1: In a cluster-randomized crossover trial among 6 ICUs across 3 medical
        centers, evaluate the impact of a VAP diagnostic stewardship intervention on antibiotic use,
        VAP diagnoses, and adverse events.
  
        Hypothesis: A change in unnecessary antibiotics for VAP and in VAP clinical diagnoses in the
        intervention vs. control periods across all sites, without a change in adverse events, is
        expected.
  
        Specific Aim 2: Evaluate overall impact of intervention including clinical and antibiotic
        outcomes using the "Desirability of Outcome Ranking (DOOR)/ Response Adjusted for Duration of
        Antibiotic Risk (RADAR)" methodology.
  
        Hypothesis: A change in overall patient outcomes (better DOOR ranking, accounting for
        duration of antibiotic use) in the intervention vs. control period is expected.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: This is a pragmatic cluster-randomized crossover trial in 6 adult ICUs (1 medical and 1 surgical ICU each at 3 hospitals). ICUs (clusters) will be randomized at the hospital-level (1:1) to a sequence of intervention (6 months) followed by control (6 months), or vice-versa. The study population is ventilated patients with respiratory culture orders but not meeting clinical pneumonia criteria, and organism(s) growing in respiratory culture. A research physician will evaluate likelihood of pneumonia using a standard clinical algorithm, within 24 hours of the order Mon-Fri. If pneumonia criteria are not met AND there is growth of organism(s) (except normal respiratory flora), during the intervention period, the culture report will be modified to reflect the likelihood of asymptomatic colonization instead of reporting bacterial identification. Clinicians may call the lab for identification and susceptibilities if necessary. During the control period, no modification to reporting will occur.
  primary purpose: Other
  masking: Single (Care Provider)
  masking description: Ordering care providers will not be aware if the test results are eligible for modified reporting or not.
  measure: Proportion of unnecessary antibiotic therapy
  time frame: Respiratory culture collection date through day 28 or patient discharge
  description: The primary efficacy outcome is change in proportion of unnecessary antibiotic therapy for presumed VAP in the intervention (modified reporting) period compared to control (standard reporting) period.
  Antibiotic use for VAP relative to the index respiratory culture will be classified as follows:
  Not on empiric antibiotic(s), new antibiotic started based on index respiratory culture result
  Not on empiric antibiotic(s), no new antibiotics initiated based on culture result
  On empiric antibiotic(s), changed based on index respiratory culture, completed course for VAP
  On empiric antibiotic(s), continued without change following index respiratory culture, completed course for VAP
  On empiric antibiotic(s), antibiotics discontinued based on culture results
  On empiric antibiotics(s), but this was not directed towards VAP Antibiotic use in categories a, c, and d will together be considered "unnecessary antibiotic therapy for VAP treatment".
  measure: Antibiotic consumption
  time frame: Measured over the 6 month control period and the 6 month intervention period
  description: To understand the impact on antibiotic use in ICU patients, we will measure the duration of antibiotic therapy for study patients, unit-level total antibiotic days of therapy (DOTs) standardized to patient census, and unit-level respiratory antibiotic days of therapy (DOTs) standardized to patient census.
  measure: Frequency of clinical diagnosis of VAP and tracheobronchitis
  time frame: Measured within the 7 days after the index respiratory culture
  description: Measurement of this outcome will help understand how modification of reporting would influence the likelihood of a patient receiving a diagnosis of VAP. The clinical diagnosis of VAP is an intermediate outcome that precedes the endpoint of antibiotic use. Because there are no consensus definitions for VAP, we will use the treating clinician's documentation of pneumonia or VAP and treatment for those conditions to capture this outcome. Similarly, clinical diagnosis of tracheobronchitis within 7 days after the index culture will also be recorded.
  measure: Antibiotic use outcome sensitivity analysis
  time frame: Measured within the 7 days after the index respiratory culture
  description: We will perform a sensitivity analysis of the impact on antibiotic use outcomes after excluding patients diagnosed with tracheobronchitis within 7 days of index culture. The hypothesis is that the intervention will have limited impact on those diagnosed and treated for tracheobronchitis, and thus, we may see a larger difference between intervention and control when excluding patients with diagnoses of tracheobronchitis.
  measure: Number of Ventilator-free days
  time frame: Measured within the 28 days after the index respiratory culture
  description: Ventilator-free days is defined as the number of calendar days within 28 days after the index respiratory culture on which the patient was not mechanically ventilated. Any patient dying within 28 days of the index respiratory culture collection will be assigned zero ventilator-free days. Ventilator-free days will be compared between the intervention and control periods for all study ICUs combined, and by hospital.
  measure: Frequency of provider requests for complete reports
  time frame: Measured during the 6 month intervention period
  description: Frequency of requests for complete reports in the intervention period - these data are applicable in the intervention period only. This will be a primarily descriptive analysis to help us understand if the intervention worked as intended i.e., how frequently did clinicians still want the full report with organism identification despite the nudge to consider asymptomatic colonization.
  measure: Incidence of Adverse Events
  time frame: Measured within the 7 days after the index respiratory culture
  description: Death, bacteremia, and septic shock (from any cause) within 7 days of the index culture order will be recorded as potential significant adverse events from a delayed or missed true VAP diagnosis or delay in initiation of appropriate antimicrobial therapy. Two-person adjudication will be used to determine whether the above events were attributed to the intervention, during the intervention period. Rates of these events will be compared between intervention and control periods individually for each event, and as a combined adverse event outcome.
  measure: Desirability of Outcome Ranking (DOOR)/Response Adjusted for Duration of Antibiotic Risk (RADAR)
  time frame: Measured within the 28 days after the index respiratory culture
  description: The clinical outcome of a participant will be ranked from most to least desirable outcome, to obtain a 5-level ordinal outcome. We will conduct a series of pairwise comparisons of each intervention patient to each control patient using two rules: When comparing patients with different overall clinical outcomes, the patient with a better overall clinical outcome based on pre-specified ordered ranks is determined to have the better outcome. When comparing two patients who have the same rank based on overall clinical outcome, the patient with a shorter course of antibiotics has the better outcome. The DOOR/RADAR probability represents the probability that a randomly selected participant who received the intervention (modified reporting) has a better overall outcome than a randomly selected participant who received standard reporting (control), accounting for antibiotic duration of therapy.
  arm group label: Control Period
  arm group type: No Intervention
  description: Laboratory reporting of respiratory cultures will continue per regular or routine laboratory protocols (standard reporting).
  arm group label: Intervention
  arm group type: Other
  description: The lab will publish a modified report for respiratory cultures which do not meet clinical criteria for pneumonia and have growth of organisms (other than normal respiratory flora). The modified report will include the likelihood of colonization instead of reporting bacterial identification.
  intervention type: Other
  intervention name: Modified lab reporting
  description: If appropriateness of culturing i.e., clinical criteria for pneumonia testing does not meet the algorithm AND there is growth of one or more organism(s) that are not considered normal upper respiratory flora, during the intervention period, the result will be modified to reflect the likelihood of asymptomatic colonization.
  arm group label: Intervention
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Michelle Newman, BSN
  phone: 4107060933
  email: mnewman@som.umaryland.edu
  last name: Surbhi Leekha, MD
  phone: 4107066125
  email: sleekha@som.umaryland.edu
  responsible party type: Principal Investigator
  investigator affiliation: University of Maryland, Baltimore
  investigator full name: Surbhi Leekha
  investigator title: Professor
  mesh term: Pneumonia
  mesh term: Pneumonia, Ventilator-Associated
  sharing ipd: No
  provided document: 