<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/NCT03288311</url>
  </required_header>
  <id_info>
    <org_study_id>170650</org_study_id>
    <nct_id>NCT03288311</nct_id>
  </id_info>
  <brief_title>Protocolized Post-Extubation Respiratory Support Study</brief_title>
  <acronym>PROPER</acronym>
  <official_title>Protocolized Post-Extubation Respiratory Support (PROPER) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</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>
      Invasive mechanical ventilation is common in the medical intensive care unit, and the period&#xD;
      of time following extubation remains high risk as 11 to 15% of patients require reintubation&#xD;
      after their first extubation. Reintubation is associated with increased rates of nosocomial&#xD;
      infection and is an independent predictor of mortality. Non-invasive ventilation and high&#xD;
      flow nasal cannula are the only therapies that have been shown to reduce the rate of&#xD;
      reintubation. Recent clinical trials suggest that all patients might benefit from some form&#xD;
      of post-extubation respiratory support, but use of these therapies in usual care remains low.&#xD;
      PROPER is a cluster-randomized, multiple-crossover trial comparing a respiratory therapist&#xD;
      driven protocol to provide post-extubation respiratory support to all patients, compared to&#xD;
      usual care. The trial will enroll patients undergoing extubation in the Medical ICU at&#xD;
      Vanderbilt from October 2017 until March 2019. The primary outcome will be reintubation&#xD;
      within 96 hours.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PROPER is a prospective, pragmatic, cluster-randomized, multiple-crossover trial comparing a&#xD;
      respiratory therapist driven protocol for post-extubation respiratory support to usual care.&#xD;
      The primary outcome will be reintubation by 96 hours. All adults (age 18 or older) who&#xD;
      receive at least 12 hours of mechanical ventilation and are extubated in the Vanderbilt&#xD;
      Medical ICU will be enrolled in the trial. The ICU will be divided into 2 clusters, based on&#xD;
      the geographic areas covered by the two respiratory therapist dedicated to that ICU. The&#xD;
      study will occur in three month blocks. One cluster will be randomized to receive&#xD;
      protocolized post-extubation respiratory support (as prescribed by a protocol and delivered&#xD;
      by a respiratory therapist), while the other cluster receives usual care, which can include&#xD;
      post-extubation respiratory support when requested by the clinical team. At the end of three&#xD;
      months, the clusters will cross-over, such that each cluster will spend half of the study&#xD;
      receiving protocolized post-extubation respiratory and half of the study receiving usual&#xD;
      care. It is anticipated that approximately 630 patients will be enrolled from the medical ICU&#xD;
      during the 18 month study period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">April 28, 2019</completion_date>
  <primary_completion_date type="Actual">March 31, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reintubation</measure>
    <time_frame>within 96 hours of extubation</time_frame>
    <description>Any placement of an endotracheal tube for any indication within 96 hours of extubation, censored at the first of hospital discharge or 96 hours after extubation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause in-hospital death</measure>
    <time_frame>from extubation to discharge or 28 days post-extubation</time_frame>
    <description>All cause mortality, censored at the first of hospital discharge or 28 days after extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU-free days</measure>
    <time_frame>from extubation to discharge or 28 days post-extubation</time_frame>
    <description>number of days alive from final ICU transfer until study day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator-free days</measure>
    <time_frame>from extubation to discharge or 28 days post-extubation</time_frame>
    <description>number of days alive from final invasive mechanical ventilation until study day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reintubation</measure>
    <time_frame>from extubation to discharge or 28 days post-extubation</time_frame>
    <description>Time from extubation to reintubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Indication for re-intubation</measure>
    <time_frame>within 96 hours of extubation</time_frame>
    <description>Proportion of patients in each group with respiratory vs non-respiratory indications for reintubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laryngeal edema requiring reintubation</measure>
    <time_frame>within 96 hours of extubation</time_frame>
    <description>Proportion of patients in each group with laryngeal edema as the indication for reintubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delirium</measure>
    <time_frame>within 96 hours of extubation</time_frame>
    <description>As defined by CAM-ICU score and reported by bedside nurse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Agitation</measure>
    <time_frame>within 96 hours of extubation</time_frame>
    <description>As defined by RAS score and reported by bedside nurse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lowest S/F ratio</measure>
    <time_frame>between 0-6 hours, 6-12 hours, and 12-24 hours after extubation</time_frame>
    <description>Lowest ratio of O2 saturation to concentration inhaled oxygen (FIO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Highest respiratory rate</measure>
    <time_frame>between 0-6 hours, 6-12 hours, and 12-24 hours after extubation</time_frame>
    <description>Highest respiratory rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of HFNC or NIV beyond 24 hours post-extubation</measure>
    <time_frame>from extubation to 96 hours post-extubation</time_frame>
    <description>Use of non-invasive ventilation or high flow nasal cannula beyond 24 hours post-extubation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">751</enrollment>
  <condition>Mechanical Ventilation Complication</condition>
  <condition>Acute Respiratory Failure</condition>
  <condition>Intubation Complication</condition>
  <arm_group>
    <arm_group_label>Protocolized Post-extubation Respiratory Support</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Protocolized post-extubation respiratory support</intervention_name>
    <description>Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning</description>
    <arm_group_label>Protocolized Post-extubation Respiratory Support</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Usual Care</intervention_name>
    <description>Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team.</description>
    <arm_group_label>Usual Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient is located in a participating unit&#xD;
&#xD;
          2. Patient undergoing extubation from mechanical ventilation&#xD;
&#xD;
          3. Patient has been receiving mechanical ventilation for at least 12 hours&#xD;
&#xD;
          4. Age ≥ 18 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient is receiving ventilation via a tracheostomy&#xD;
&#xD;
          2. Patient is being extubated to comfort measures or has &quot;Do Not Reintubate&quot; order in&#xD;
             place at the time of extubation&#xD;
&#xD;
          3. Patient has required reintubation after a prior attempt at extubation during this&#xD;
             hospitalization&#xD;
&#xD;
          4. Unplanned or self-extubation, where immediate reintubation is deemed necessary by the&#xD;
             clinical team&#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_official>
    <last_name>Todd W Rice, MD, MSc</last_name>
    <role>Study Chair</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>February 21, 2020</last_update_submitted>
  <last_update_submitted_qc>February 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Jonathan Casey</investigator_full_name>
    <investigator_title>Pulmonary and Critical Care Medicine Research Fellow</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data will be available following publication of the primary trial results</ipd_time_frame>
    <ipd_access_criteria>Data dictionary will be available upon requests. Requests for deidentified patient-level data will be reviewed by the trial steering committee. Sharing of deidentified data will require approval of proposed secondary analysis and a signed data use agreement.</ipd_access_criteria>
  </patient_data>
  <pending_results>
    <submitted>February 3, 2022</submitted>
    <returned>April 8, 2022</returned>
    <submitted>August 4, 2022</submitted>
    <returned>August 5, 2022</returned>
  </pending_results>
  <!-- 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/NCT03288311
org study id: 170650
nct id: NCT03288311
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Invasive mechanical ventilation is common in the medical intensive care unit, and the period
      of time following extubation remains high risk as 11 to 15% of patients require reintubation
      after their first extubation. Reintubation is associated with increased rates of nosocomial
      infection and is an independent predictor of mortality. Non-invasive ventilation and high
      flow nasal cannula are the only therapies that have been shown to reduce the rate of
      reintubation. Recent clinical trials suggest that all patients might benefit from some form
      of post-extubation respiratory support, but use of these therapies in usual care remains low.
      PROPER is a cluster-randomized, multiple-crossover trial comparing a respiratory therapist
      driven protocol to provide post-extubation respiratory support to all patients, compared to
      usual care. The trial will enroll patients undergoing extubation in the Medical ICU at
      Vanderbilt from October 2017 until March 2019. The primary outcome will be reintubation
      within 96 hours.
PROPER is a prospective, pragmatic, cluster-randomized, multiple-crossover trial comparing a
      respiratory therapist driven protocol for post-extubation respiratory support to usual care.
      The primary outcome will be reintubation by 96 hours. All adults (age 18 or older) who
      receive at least 12 hours of mechanical ventilation and are extubated in the Vanderbilt
      Medical ICU will be enrolled in the trial. The ICU will be divided into 2 clusters, based on
      the geographic areas covered by the two respiratory therapist dedicated to that ICU. The
      study will occur in three month blocks. One cluster will be randomized to receive
      protocolized post-extubation respiratory support (as prescribed by a protocol and delivered
      by a respiratory therapist), while the other cluster receives usual care, which can include
      post-extubation respiratory support when requested by the clinical team. At the end of three
      months, the clusters will cross-over, such that each cluster will spend half of the study
      receiving protocolized post-extubation respiratory and half of the study receiving usual
      care. It is anticipated that approximately 630 patients will be enrolled from the medical ICU
      during the 18 month study period.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Reintubation
time frame: within 96 hours of extubation
description: Any placement of an endotracheal tube for any indication within 96 hours of extubation, censored at the first of hospital discharge or 96 hours after extubation
measure: All-cause in-hospital death
time frame: from extubation to discharge or 28 days post-extubation
description: All cause mortality, censored at the first of hospital discharge or 28 days after extubation
measure: ICU-free days
time frame: from extubation to discharge or 28 days post-extubation
description: number of days alive from final ICU transfer until study day 28
measure: Ventilator-free days
time frame: from extubation to discharge or 28 days post-extubation
description: number of days alive from final invasive mechanical ventilation until study day 28
measure: Time to reintubation
time frame: from extubation to discharge or 28 days post-extubation
description: Time from extubation to reintubation
measure: Indication for re-intubation
time frame: within 96 hours of extubation
description: Proportion of patients in each group with respiratory vs non-respiratory indications for reintubation
measure: Laryngeal edema requiring reintubation
time frame: within 96 hours of extubation
description: Proportion of patients in each group with laryngeal edema as the indication for reintubation
measure: Delirium
time frame: within 96 hours of extubation
description: As defined by CAM-ICU score and reported by bedside nurse
measure: Agitation
time frame: within 96 hours of extubation
description: As defined by RAS score and reported by bedside nurse
measure: Lowest S/F ratio
time frame: between 0-6 hours, 6-12 hours, and 12-24 hours after extubation
description: Lowest ratio of O2 saturation to concentration inhaled oxygen (FIO2)
measure: Highest respiratory rate
time frame: between 0-6 hours, 6-12 hours, and 12-24 hours after extubation
description: Highest respiratory rate
measure: Use of HFNC or NIV beyond 24 hours post-extubation
time frame: from extubation to 96 hours post-extubation
description: Use of non-invasive ventilation or high flow nasal cannula beyond 24 hours post-extubation
arm group label: Protocolized Post-extubation Respiratory Support
arm group type: Active Comparator
description: Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning
arm group label: Usual Care
arm group type: Active Comparator
description: Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team.
intervention type: Other
intervention name: Protocolized post-extubation respiratory support
description: Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning
arm group label: Protocolized Post-extubation Respiratory Support
intervention type: Other
intervention name: Usual Care
description: Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team.
arm group label: Usual Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Todd W Rice, MD, MSc
role: Study Chair
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Jonathan Casey
investigator title: Pulmonary and Critical Care Medicine Research Fellow
mesh term: Respiratory Insufficiency
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data will be available following publication of the primary trial results
ipd access criteria: Data dictionary will be available upon requests. Requests for deidentified patient-level data will be reviewed by the trial steering committee. Sharing of deidentified data will require approval of proposed secondary analysis and a signed data use agreement.
submitted: February 3, 2022
returned: April 8, 2022
submitted: August 4, 2022
returned: August 5, 2022