<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/NCT02265198</url>
  </required_header>
  <id_info>
    <org_study_id>BG03-018</org_study_id>
    <nct_id>NCT02265198</nct_id>
  </id_info>
  <brief_title>Relationship of Pulmonary Contusion to Pulmonary Inflammation and Incidence of Acute Respiratory Distress Syndrome</brief_title>
  <official_title>Relationship of Pulmonary Contusion Morphology to Pulmonary Inflammation and Incidence of Acute Respiratory Distress Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pulmonary contusion (PC) is a significant problem after blunt trauma that may often lead to&#xD;
      acute respiratory distress syndrome (ARDS) and in some patients, death. Although the&#xD;
      pathophysiology is incompletely understood, it is clear that there is a biochemical process&#xD;
      involving changes in the inflammatory milieu after contusion which occurs in addition to&#xD;
      simple direct mechanical injury to the lung. The relationship of severity of contusion on&#xD;
      imaging, disturbances in the inflammatory phenotype, and outcome is unknown. This is a&#xD;
      prospective, observational study which will evaluate the size and severity of contusion as&#xD;
      measured on chest computed tomography (CT). Inflammatory mediators will be measured in the&#xD;
      bronchoalveolar lavage (BAL) and in the serum of patients with pulmonary contusion to define&#xD;
      the inflammatory nature of the post-contusion lung. The degree of abnormality within the&#xD;
      inflammatory parameters will be correlated with lung contusion size and subsequent patient&#xD;
      outcomes. These data will be compared to other patient groups: 1) Trauma patients without&#xD;
      chest injury who are mechanically ventilated; 2) Uninjured patients undergoing elective&#xD;
      surgical procedures that will require intubation and mechanical ventilation; 3) Patients in&#xD;
      the Medical ICU who are mechanically ventilated with acute respiratory failure.&#xD;
&#xD;
      The hypothesis tested within this study is resolution of lung injury is dependent upon the&#xD;
      presence of Tregs in the alveolar space.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted at Wake Forest University Baptist Medical Center and will enroll&#xD;
      40 patients in the PC study group, 20 patients in each control group, and 20 MICU patients.&#xD;
      Recruitment will occur over two years. The sample size was determined by identifying the mean&#xD;
      number of patients with PC admitted (38) to WFUBMC per year. Using Whittemore's formula, this&#xD;
      sample size will be adequate to detect a significant odds ratio of 5 (alpha &lt;0.05) with&#xD;
      respect to increase in acute lung injury or ARDS risk in patients with &gt; 20 % total lung&#xD;
      volume contusion with approximately 85% power. The odds ratio for this population in&#xD;
      developing acute lung injury or ARDS in a previous study was 16.666. Eligible subjects for&#xD;
      study group will be patients with PC on admission CT; eligible subjects for control group #1&#xD;
      (CG1) are non-injured patients without PC undergoing a standard general surgical procedure;&#xD;
      eligible subjects for control group #2 (CG2) are non-chest, non-PC trauma patients who are&#xD;
      admitted intubated to the trauma ICU; eligible MICU subjects are patients on mechanical&#xD;
      ventilation admitted to the Medical ICU with acute respiratory failure.&#xD;
&#xD;
      Informed consent for study group, CG2, and the MICU group will generally be obtained from&#xD;
      family members as most patients will be unconscious or sedated. If the patient is alert, the&#xD;
      study will be explained to both the patient and family. Informed consent for CG1 will be&#xD;
      obtained from the patient and family members in Surgery Clinic prior to elective procedures.&#xD;
      An initial blood sample will be obtained on all persons in the study group, CG2, and, if the&#xD;
      patient is ventilated, a BAL will be obtained after signing of the informed consent by the&#xD;
      patient or LAR. Blood samples and pulmonary samples will be obtained on CG1 patients after&#xD;
      obtaining signed informed consent, in the operating theater, after they are sedated and&#xD;
      intubated, though before their elective procedure. Blood and pulmonary samples will be&#xD;
      obtained from MICU subjects after obtaining signed informed consent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Volume of Pulmonary Contusion on CT scan</measure>
    <time_frame>14 days</time_frame>
    <description>Measured volume of pulmonary contusion on CT scan correlates with increase in ventilator free days, ICU days, hospital days, and mortality</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of serum inflammatory mediator levels in BAL fluid</measure>
    <time_frame>14 days</time_frame>
    <description>Volume of serum inflammatory mediator levels correlates with increase in ventilator free days, ICU days, hospital days, and mortality</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Presence of Tregs in BAL fluid</measure>
    <time_frame>14 days</time_frame>
    <description>Measure presence of Tregs in BAL (% or absolute) to determine if positively correlated with reduced lung injury duration (increase in ventilator free days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of activated neutrophils in BAL fluid</measure>
    <time_frame>14 day</time_frame>
    <description>measure neutrophil phenotypes in numbers to determine correlation with vent free days and mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appearance of M2 macrophage phenotypes in BAL fluid</measure>
    <time_frame>14 day</time_frame>
    <description>measure macrophage phenotype (M1 or M2) numbers and percent to determine correlation with vent free days and mortality</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">10</enrollment>
  <condition>Pulmonary Contusion</condition>
  <condition>Respiratory Failure</condition>
  <condition>ARDS</condition>
  <arm_group>
    <arm_group_label>PC Group</arm_group_label>
    <description>patients with Pulmonary Contusion on chest computed tomography (CT)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group 1</arm_group_label>
    <description>Uninjured patients undergoing elective surgical procedures that will require intubation and mechanical ventilation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group 2</arm_group_label>
    <description>Trauma patients without chest injury who are mechanically ventilated</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MICU group</arm_group_label>
    <description>Patients in the Medical ICU who are mechanically ventilated with acute respiratory failure</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bronchial Alveolar Lavage - Supernatant Blood-Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study will be conducted at Wake Forest University Baptist Medical Center and will&#xD;
        enroll 40 patients in the PC study group, 20 patients in each control group, and 20 MICU&#xD;
        patients. Eligible subjects for study group will be patients with PC on admission CT;&#xD;
        eligible subjects for control group #1 (CG1) are normal patients without PC undergoing a&#xD;
        standard general surgical procedure; eligible subjects for control group #2 (CG2) are&#xD;
        non-chest, non-PC trauma patients who are admitted intubated to the trauma ICU; eligible&#xD;
        MICU subjects are patients on mechanical ventilation admitted to the Medical ICU with acute&#xD;
        respiratory failure.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 15 years old&#xD;
&#xD;
          -  Chest trauma patients&#xD;
&#xD;
          -  Medical ICU patients with respiratory failure&#xD;
&#xD;
          -  Elective surgery patients&#xD;
&#xD;
          -  Trauma or surgical ICU patients on ventilators without chest trauma/pulmonary&#xD;
             contusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age 15 years and younger&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Subjects with multiple myeloma, pheochromocytoma, homozygous sickle cell disease, or&#xD;
             thyroid disorders&#xD;
&#xD;
          -  Traumatic brain injury requiring intracranial pressure monitoring&#xD;
&#xD;
          -  Moribund status&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason Hoth, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter E Morris, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wake Forest Baptist Health</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>November 2, 2017</last_update_submitted>
  <last_update_submitted_qc>November 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulmonary Contusion</keyword>
  <keyword>ARDS</keyword>
  <keyword>Respiratory Failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Contusions</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02265198
org study id: BG03-018
nct id: NCT02265198
lead sponsor: 
has dmc: No
Pulmonary contusion (PC) is a significant problem after blunt trauma that may often lead to
      acute respiratory distress syndrome (ARDS) and in some patients, death. Although the
      pathophysiology is incompletely understood, it is clear that there is a biochemical process
      involving changes in the inflammatory milieu after contusion which occurs in addition to
      simple direct mechanical injury to the lung. The relationship of severity of contusion on
      imaging, disturbances in the inflammatory phenotype, and outcome is unknown. This is a
      prospective, observational study which will evaluate the size and severity of contusion as
      measured on chest computed tomography (CT). Inflammatory mediators will be measured in the
      bronchoalveolar lavage (BAL) and in the serum of patients with pulmonary contusion to define
      the inflammatory nature of the post-contusion lung. The degree of abnormality within the
      inflammatory parameters will be correlated with lung contusion size and subsequent patient
      outcomes. These data will be compared to other patient groups: 1) Trauma patients without
      chest injury who are mechanically ventilated; 2) Uninjured patients undergoing elective
      surgical procedures that will require intubation and mechanical ventilation; 3) Patients in
      the Medical ICU who are mechanically ventilated with acute respiratory failure.

      The hypothesis tested within this study is resolution of lung injury is dependent upon the
      presence of Tregs in the alveolar space.
The study will be conducted at Wake Forest University Baptist Medical Center and will enroll
      40 patients in the PC study group, 20 patients in each control group, and 20 MICU patients.
      Recruitment will occur over two years. The sample size was determined by identifying the mean
      number of patients with PC admitted (38) to WFUBMC per year. Using Whittemore's formula, this
      sample size will be adequate to detect a significant odds ratio of 5 (alpha <0.05) with
      respect to increase in acute lung injury or ARDS risk in patients with > 20 % total lung
      volume contusion with approximately 85% power. The odds ratio for this population in
      developing acute lung injury or ARDS in a previous study was 16.666. Eligible subjects for
      study group will be patients with PC on admission CT; eligible subjects for control group #1
      (CG1) are non-injured patients without PC undergoing a standard general surgical procedure;
      eligible subjects for control group #2 (CG2) are non-chest, non-PC trauma patients who are
      admitted intubated to the trauma ICU; eligible MICU subjects are patients on mechanical
      ventilation admitted to the Medical ICU with acute respiratory failure.

      Informed consent for study group, CG2, and the MICU group will generally be obtained from
      family members as most patients will be unconscious or sedated. If the patient is alert, the
      study will be explained to both the patient and family. Informed consent for CG1 will be
      obtained from the patient and family members in Surgery Clinic prior to elective procedures.
      An initial blood sample will be obtained on all persons in the study group, CG2, and, if the
      patient is ventilated, a BAL will be obtained after signing of the informed consent by the
      patient or LAR. Blood samples and pulmonary samples will be obtained on CG1 patients after
      obtaining signed informed consent, in the operating theater, after they are sedated and
      intubated, though before their elective procedure. Blood and pulmonary samples will be
      obtained from MICU subjects after obtaining signed informed consent.
observational model: Case-Control
time perspective: Prospective
measure: Volume of Pulmonary Contusion on CT scan
time frame: 14 days
description: Measured volume of pulmonary contusion on CT scan correlates with increase in ventilator free days, ICU days, hospital days, and mortality
measure: Volume of serum inflammatory mediator levels in BAL fluid
time frame: 14 days
description: Volume of serum inflammatory mediator levels correlates with increase in ventilator free days, ICU days, hospital days, and mortality
measure: Presence of Tregs in BAL fluid
time frame: 14 days
description: Measure presence of Tregs in BAL (% or absolute) to determine if positively correlated with reduced lung injury duration (increase in ventilator free days)
measure: Presence of activated neutrophils in BAL fluid
time frame: 14 day
description: measure neutrophil phenotypes in numbers to determine correlation with vent free days and mortality
measure: Appearance of M2 macrophage phenotypes in BAL fluid
time frame: 14 day
description: measure macrophage phenotype (M1 or M2) numbers and percent to determine correlation with vent free days and mortality
arm group label: PC Group
description: patients with Pulmonary Contusion on chest computed tomography (CT)
arm group label: Control Group 1
description: Uninjured patients undergoing elective surgical procedures that will require intubation and mechanical ventilation
arm group label: Control Group 2
description: Trauma patients without chest injury who are mechanically ventilated
arm group label: MICU group
description: Patients in the Medical ICU who are mechanically ventilated with acute respiratory failure
Bronchial Alveolar Lavage - Supernatant Blood-Serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Jason Hoth, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
last name: Peter E Morris, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Respiratory Insufficiency
mesh term: Acute Lung Injury
mesh term: Inflammation
mesh term: Contusions
sharing ipd: No