<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/NCT04438187</url>
  </required_header>
  <id_info>
    <org_study_id>145059</org_study_id>
    <nct_id>NCT04438187</nct_id>
  </id_info>
  <brief_title>Trial of Antimicrobial Restraint in Presumed Pneumonia</brief_title>
  <acronym>TARPP</acronym>
  <official_title>Trial of Antimicrobial Restraint in Presumed Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Kansas Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Western Michigan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kansas Medical Center</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>
      The objective of this cluster-randomized crossover study is to determine the effect of&#xD;
      delaying antimicrobial initiation until objective microbiologic data is obtained in patients&#xD;
      with presumed ICU-acquired pneumonia without septic shock.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will involve 8 centers is to determine the effect of delaying antimicrobial&#xD;
      initiation until objective microbiologic data is obtained in patients with presumed&#xD;
      ICU-acquired pneumonia without septic shock. The study team will compare two sequential&#xD;
      4-month periods in each unit, one 'aggressive' antimicrobial initiation period and one&#xD;
      'conservative' antimicrobial initiation period.&#xD;
&#xD;
      This study will serve the following specific aims:&#xD;
&#xD;
      Specific Aim 1: To determine feasibility of a larger multicenter study of the same design as&#xD;
      well as assess protocol adherence across multiple centers.&#xD;
&#xD;
      Specific Aim 2: Prospectively determine the all-cause, in-hospital mortality for all patients&#xD;
      with suspected pneumonia who were treated under either an aggressive or conservative&#xD;
      antimicrobial initiation protocol.&#xD;
&#xD;
      Specific Aim 3: Prospectively determine antimicrobial initiation rates, total days of&#xD;
      antimicrobial administration, hospital and ICU length of stay, and ventilator-free alive days&#xD;
      for patients treated under each protocol.&#xD;
&#xD;
      Specific Aim 4: To survey physicians that participated in the study to assess their feelings&#xD;
      about the study including level of comfort starting antimicrobials aggressively, level of&#xD;
      comfort withholding antimicrobials until definitive evidence of infection, perceived protocol&#xD;
      adherence, perceived importance of the study, and willingness to participate in other studies&#xD;
      of its kind (to be performed after closure of the clinical portion of the study).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2021</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">January 6, 2022</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 will be a pragmatic, before-and-after, cluster-randomized, protocol crossover study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>protocol adherence</measure>
    <time_frame>by time of culture finalization or 1 week</time_frame>
    <description>as a pilot study the primary outcome will be protocol adherence as defined by using the criteria below:&#xD;
Aggressive Protocol:&#xD;
Failure to send appropriate culture before initiation of antimicrobials in the absence of septic shock&#xD;
Failure to stop antimicrobials in the absence of pneumonia or other documented infection after 72 hours.&#xD;
Conservative Protocol:&#xD;
Failure to send appropriate culture&#xD;
Initiation of antimicrobials (in the absence of septic shock, new onset or worsening organ dysfunction, or other indicated source of infection) without any objective evidence of pneumonia.&#xD;
Failure to initiate antimicrobials in the setting of objective evidence of pneumonia.&#xD;
Failure to stop antimicrobials in the absence of other documented infection if final cultures return as negative.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>until hospital discharge or 1 year</time_frame>
    <description>All-cause, by treatment protocol assignment (intent-to-treat), ICU mortality, pneumonia-related</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of antimicrobials administered</measure>
    <time_frame>until hospital discharge or 1 year</time_frame>
    <description>includes empiric, therapeutic, prophylactic, and perioperative antimicrobials</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator-free alive days</measure>
    <time_frame>until hospital discharge or 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>Until discharge from ICU or 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>until hospital discharge or 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">186</enrollment>
  <condition>Healthcare-Associated Pneumonia</condition>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Aggressive Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>If an intubated patient is suspected of having an ICU-acquired HAP/VAP during the aggressive period, antimicrobials should be initiated immediately after quantitative or semi-quantitative endobronchial cultures are sent regardless of clinical status. This will include patients who, as determined by the attending intensivist, are in sepsis or septic shock. If, after 72 hours, cultures and other clinical data do not point to a pneumonia, the antimicrobials should be stopped in the absence of another source of infection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conservative Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>If a patient is suspected of having an ICU-acquired HAP/VAP during the conservative period, quantitative or semi-quantitative endobronchial cultures should be sent. If the patient is in septic shock persistent hypotension requiring vasoactive medications to maintain mean arterial pressure (MAP) ≥65 mm HG or persistent lactic acidosis (&gt;2 mmol/L) despite adequate resuscitation) antimicrobials will be initiated immediately. If the patient has new onset organ dysfunction that is presumed to be due to infection (sepsis) then antimicrobials will be initiated at the discretion of the attending intensivist. In the absence of septic shock or sepsis (intensivist discretion), antimicrobials will not be initiated unless objective evidence of pneumonia is present or another documented source of infection is identified mandating treatment with antimicrobials.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>antimicrobial initiation</intervention_name>
    <description>antimicrobial initiation based on protocol assignment.</description>
    <arm_group_label>Aggressive Arm</arm_group_label>
    <arm_group_label>Conservative Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Intubated patients admitted to a surgical or trauma intensive care unit that have had&#xD;
             an appropriate quantitative or semi-quantitative endobronchial sputum culture sent ≥48&#xD;
             hours into their ICU admission&#xD;
&#xD;
          -  Primary pathology managed by surgical specialty&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-intubated patients.&#xD;
&#xD;
          -  Intubated patients with concern for active infection that is not suspected to be&#xD;
             pneumonia (i.e. intra-abdominal infection, skin and soft tissue infection, urinary&#xD;
             tract infection, etc.)&#xD;
&#xD;
          -  Primary disease not surgical or traumatic in nature&#xD;
&#xD;
          -  Primary diagnosis of burns&#xD;
&#xD;
          -  Incarcerated status&#xD;
&#xD;
          -  Pregnant status or delivery during this hospitalization.&#xD;
&#xD;
          -  On active immunosuppressive medications (or taking as a home medication prior to&#xD;
             arrival)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Guidry</last_name>
    <role>Principal Investigator</role>
    <affiliation>KU Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>KU Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>November 15, 2022</last_update_submitted>
  <last_update_submitted_qc>November 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2022</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>Pneumonia</mesh_term>
    <mesh_term>Healthcare-Associated Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Infective Agents</mesh_term>
    <mesh_term>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>aggregated study results</ipd_description>
  </patient_data>
  <!-- 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/NCT04438187
org study id: 145059
nct id: NCT04438187
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this cluster-randomized crossover study is to determine the effect of
      delaying antimicrobial initiation until objective microbiologic data is obtained in patients
      with presumed ICU-acquired pneumonia without septic shock.
This study will involve 8 centers is to determine the effect of delaying antimicrobial
      initiation until objective microbiologic data is obtained in patients with presumed
      ICU-acquired pneumonia without septic shock. The study team will compare two sequential
      4-month periods in each unit, one 'aggressive' antimicrobial initiation period and one
      'conservative' antimicrobial initiation period.

      This study will serve the following specific aims:

      Specific Aim 1: To determine feasibility of a larger multicenter study of the same design as
      well as assess protocol adherence across multiple centers.

      Specific Aim 2: Prospectively determine the all-cause, in-hospital mortality for all patients
      with suspected pneumonia who were treated under either an aggressive or conservative
      antimicrobial initiation protocol.

      Specific Aim 3: Prospectively determine antimicrobial initiation rates, total days of
      antimicrobial administration, hospital and ICU length of stay, and ventilator-free alive days
      for patients treated under each protocol.

      Specific Aim 4: To survey physicians that participated in the study to assess their feelings
      about the study including level of comfort starting antimicrobials aggressively, level of
      comfort withholding antimicrobials until definitive evidence of infection, perceived protocol
      adherence, perceived importance of the study, and willingness to participate in other studies
      of its kind (to be performed after closure of the clinical portion of the study).
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This will be a pragmatic, before-and-after, cluster-randomized, protocol crossover study.
primary purpose: Treatment
masking: None (Open Label)
measure: protocol adherence
time frame: by time of culture finalization or 1 week
description: as a pilot study the primary outcome will be protocol adherence as defined by using the criteria below:
Aggressive Protocol:
Failure to send appropriate culture before initiation of antimicrobials in the absence of septic shock
Failure to stop antimicrobials in the absence of pneumonia or other documented infection after 72 hours.
Conservative Protocol:
Failure to send appropriate culture
Initiation of antimicrobials (in the absence of septic shock, new onset or worsening organ dysfunction, or other indicated source of infection) without any objective evidence of pneumonia.
Failure to initiate antimicrobials in the setting of objective evidence of pneumonia.
Failure to stop antimicrobials in the absence of other documented infection if final cultures return as negative.
measure: In-hospital mortality
time frame: until hospital discharge or 1 year
description: All-cause, by treatment protocol assignment (intent-to-treat), ICU mortality, pneumonia-related
measure: Days of antimicrobials administered
time frame: until hospital discharge or 1 year
description: includes empiric, therapeutic, prophylactic, and perioperative antimicrobials
measure: Ventilator-free alive days
time frame: until hospital discharge or 1 year
measure: ICU length of stay
time frame: Until discharge from ICU or 1 year
measure: Hospital length of stay
time frame: until hospital discharge or 1 year
arm group label: Aggressive Arm
arm group type: Other
description: If an intubated patient is suspected of having an ICU-acquired HAP/VAP during the aggressive period, antimicrobials should be initiated immediately after quantitative or semi-quantitative endobronchial cultures are sent regardless of clinical status. This will include patients who, as determined by the attending intensivist, are in sepsis or septic shock. If, after 72 hours, cultures and other clinical data do not point to a pneumonia, the antimicrobials should be stopped in the absence of another source of infection.
arm group label: Conservative Arm
arm group type: Other
description: If a patient is suspected of having an ICU-acquired HAP/VAP during the conservative period, quantitative or semi-quantitative endobronchial cultures should be sent. If the patient is in septic shock persistent hypotension requiring vasoactive medications to maintain mean arterial pressure (MAP) ≥65 mm HG or persistent lactic acidosis (>2 mmol/L) despite adequate resuscitation) antimicrobials will be initiated immediately. If the patient has new onset organ dysfunction that is presumed to be due to infection (sepsis) then antimicrobials will be initiated at the discretion of the attending intensivist. In the absence of septic shock or sepsis (intensivist discretion), antimicrobials will not be initiated unless objective evidence of pneumonia is present or another documented source of infection is identified mandating treatment with antimicrobials.
intervention type: Other
intervention name: antimicrobial initiation
description: antimicrobial initiation based on protocol assignment.
arm group label: Aggressive Arm
arm group label: Conservative Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Christopher Guidry
role: Principal Investigator
affiliation: KU Medical Center
facility: 
country: United States
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responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Healthcare-Associated Pneumonia
mesh term: Anti-Infective Agents
mesh term: Anti-Bacterial Agents
sharing ipd: No
ipd description: aggregated study results