<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/NCT01667666</url>
  </required_header>
  <id_info>
    <org_study_id>COMIRB #11-0706</org_study_id>
    <nct_id>NCT01667666</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Nebulized Hypertonic Saline to Attenuate Post-Traumatic Acute Lung Injury</brief_title>
  <official_title>A Clinical Study to Determine if Nebulized Hypertonic Saline Attenuates Acute Lung Injury Following Trauma and Hemorrhagic Shock</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Denver Health and Hospital Authority</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Denver Health and Hospital Authority</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the use of nebulized hypertonic saline (aerosolized salt water) as a&#xD;
      preventive treatment for post-traumatic acute lung injury (ALI). Both animal and human&#xD;
      research indicate that aerosolized salt water might help reduce harmful inflammation with&#xD;
      minimal risks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite over 40 years of investigation, acute lung injury (ALI) remains a leading cause of&#xD;
      morbidity in critically ill patients, and a disease for which there is no effective&#xD;
      pharmacologic therapy. Our group and others have focused on the anti-inflammatory effects of&#xD;
      intravenous hypertonic saline (HTS) acting on the injured endothelium with promising results&#xD;
      experimentally, but failed to confirm the benefit clinically. Recent work, however, has shown&#xD;
      that inhaled or nebulized HTS targeted at the epithelium is safe and effective in treating&#xD;
      cystic fibrosis, COPD, and neonatal bronchiolitis. Recognizing the central role of the&#xD;
      pulmonary epithelium in ALI, nebulization has the advantage of achieving high concentrations&#xD;
      of the therapy without producing systemic side effects. Thus, we hypothesize that nebulized&#xD;
      hypertonic saline will attenuate acute lung injury following trauma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low enrollment and loss of funding&#xD;
  </why_stopped>
  <start_date type="Actual">May 2012</start_date>
  <completion_date type="Actual">November 6, 2018</completion_date>
  <primary_completion_date type="Actual">November 6, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in the respiratory parameters</measure>
    <time_frame>baseline and every 6 hours for 36 hours</time_frame>
    <description>For intubated patients - A decrease greater than 20% in PaO2/FiO2 (P/F) ratios will trigger DSMB review. For not intubated patients - a) the need to increase FiO2 by 10% (approximate 4 liter/minute increase) to maintain a peripheral oxygen saturation (SaO2) of 90% during nebulizer treatment; b) evidence of respiratory distress (as documented in the chart by the patient's attending) during nebulizer treatment; and c) respiratory insufficiency requiring intubation and mechanical ventilation at any point will trigger DSMB review.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>death within 28 days</measure>
    <time_frame>28 days or discharge</time_frame>
    <description>If the rate of death within 28 days for this patient population is less than 50% the expected rate for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lung dysfunction scores</measure>
    <time_frame>baseline and 28 days or discharge</time_frame>
    <description>Denver lung MOF score will be measure daily until discharge or 28 days, which ever is first. For every 5 patients, if the rate of lung dysfunction for this patient population is less than 50% the expected rate based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ventilator-free days (VFD)</measure>
    <time_frame>baseline and 28 days or discharge</time_frame>
    <description>Ventilator free days will be tracked with 28 days as a reference. If the number of VFDs for this patient population is greater than one standard deviation of the predicted value for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MOF scores (Denver MOF score)</measure>
    <time_frame>28 days or discharge</time_frame>
    <description>Denver MOF score will be recorded daily until discharge or 28 days, which ever is sooner. for every 5 patients, if the rate of MOF for this patient population is greater than one standard deviation of the predicted value for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Acute Lung Injury</condition>
  <condition>Adult Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>Nebulized HTS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The first 5 patients will receive 3% Nebulized hypertonic saline, the second 5 patients will receive 4.5% Nebulized hypertonic saline, the third group 6% Nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% Nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nebulized hypertonic saline</intervention_name>
    <description>The first 5 patients will receive 3% hypertonic saline in a nebulizer, the second 5 patients will receive 4.5% nebulized hypertonic saline, the third group 6% nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.</description>
    <arm_group_label>Nebulized HTS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult 18 ≤ age ≤ 65&#xD;
&#xD;
          -  trauma with a 9 ≤ NISS ≤ 36&#xD;
&#xD;
          -  ≤10 units of RBC in the first 6 hours (as this is a major risk factor for ARDS and MOF&#xD;
             in this population)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Direct or indirect lung injury&#xD;
&#xD;
          -  Elevated intracranial pressure requiring treatment, including but not limited to&#xD;
             mannitol, intravenous hypertonic saline, and ventricular drainage&#xD;
&#xD;
          -  History of severe chronic respiratory disease&#xD;
&#xD;
          -  Child-Pugh Class C liver failure&#xD;
&#xD;
          -  Prisoners&#xD;
&#xD;
          -  Pregnant women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ernest E Moore, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Denver Health and Hospital Authority</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Denver Health Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>January 4, 2019</last_update_submitted>
  <last_update_submitted_qc>January 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Denver Health and Hospital Authority</investigator_affiliation>
    <investigator_full_name>Ernest E. Moore, MD</investigator_full_name>
    <investigator_title>Professor of Surgery</investigator_title>
  </responsible_party>
  <keyword>trauma</keyword>
  <keyword>acute lung injury</keyword>
  <keyword>adult respiratory distress syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Wounds and Injuries</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/NCT01667666
org study id: COMIRB #11-0706
nct id: NCT01667666
lead sponsor: 
collaborator: 
has dmc: Yes
This study evaluates the use of nebulized hypertonic saline (aerosolized salt water) as a
      preventive treatment for post-traumatic acute lung injury (ALI). Both animal and human
      research indicate that aerosolized salt water might help reduce harmful inflammation with
      minimal risks.
Despite over 40 years of investigation, acute lung injury (ALI) remains a leading cause of
      morbidity in critically ill patients, and a disease for which there is no effective
      pharmacologic therapy. Our group and others have focused on the anti-inflammatory effects of
      intravenous hypertonic saline (HTS) acting on the injured endothelium with promising results
      experimentally, but failed to confirm the benefit clinically. Recent work, however, has shown
      that inhaled or nebulized HTS targeted at the epithelium is safe and effective in treating
      cystic fibrosis, COPD, and neonatal bronchiolitis. Recognizing the central role of the
      pulmonary epithelium in ALI, nebulization has the advantage of achieving high concentrations
      of the therapy without producing systemic side effects. Thus, we hypothesize that nebulized
      hypertonic saline will attenuate acute lung injury following trauma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: change in the respiratory parameters
time frame: baseline and every 6 hours for 36 hours
description: For intubated patients - A decrease greater than 20% in PaO2/FiO2 (P/F) ratios will trigger DSMB review. For not intubated patients - a) the need to increase FiO2 by 10% (approximate 4 liter/minute increase) to maintain a peripheral oxygen saturation (SaO2) of 90% during nebulizer treatment; b) evidence of respiratory distress (as documented in the chart by the patient's attending) during nebulizer treatment; and c) respiratory insufficiency requiring intubation and mechanical ventilation at any point will trigger DSMB review.
measure: death within 28 days
time frame: 28 days or discharge
description: If the rate of death within 28 days for this patient population is less than 50% the expected rate for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.
measure: lung dysfunction scores
time frame: baseline and 28 days or discharge
description: Denver lung MOF score will be measure daily until discharge or 28 days, which ever is first. For every 5 patients, if the rate of lung dysfunction for this patient population is less than 50% the expected rate based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.
measure: ventilator-free days (VFD)
time frame: baseline and 28 days or discharge
description: Ventilator free days will be tracked with 28 days as a reference. If the number of VFDs for this patient population is greater than one standard deviation of the predicted value for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.
measure: MOF scores (Denver MOF score)
time frame: 28 days or discharge
description: Denver MOF score will be recorded daily until discharge or 28 days, which ever is sooner. for every 5 patients, if the rate of MOF for this patient population is greater than one standard deviation of the predicted value for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered
arm group label: Nebulized HTS
arm group type: Experimental
description: The first 5 patients will receive 3% Nebulized hypertonic saline, the second 5 patients will receive 4.5% Nebulized hypertonic saline, the third group 6% Nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% Nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.
intervention type: Drug
intervention name: Nebulized hypertonic saline
description: The first 5 patients will receive 3% hypertonic saline in a nebulizer, the second 5 patients will receive 4.5% nebulized hypertonic saline, the third group 6% nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.
arm group label: Nebulized HTS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ernest E Moore, MD
role: Principal Investigator
affiliation: Denver Health and Hospital Authority
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Denver Health and Hospital Authority
investigator full name: Ernest E. Moore, MD
investigator title: Professor of Surgery
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Lung Injury
mesh term: Acute Lung Injury
mesh term: Wounds and Injuries