<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/NCT04503057</url>
  </required_header>
  <id_info>
    <org_study_id>PEx ARDS</org_study_id>
    <nct_id>NCT04503057</nct_id>
  </id_info>
  <brief_title>Exhaled Breath Particles as a Clinical Indicator for Lung Injury and Acute Respiratory Distress Syndrome (ARDS)</brief_title>
  <official_title>Exhaled Breath Particles as a Clinical Indicator for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) in Coronavirus (Covid-19) Positive and Negative Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lund University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lund University Hospital</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>
      Acute Respiratory Distress Syndrome (ARDS) reflects the hallmark of the critical course of&#xD;
      coronavirus (COVID19). The investigators have recently shown that Exhaled Breath Particles&#xD;
      (EBP) measured as particle flow rate (PFR) from the airways could be used as a noninvasive&#xD;
      real-time early detection method for primary graft dysfunction (which bears a&#xD;
      pathophysiological resemblance to ARDS) in lung transplant patients. The investigators have&#xD;
      also previously demonstrated the utility of PFR in early detection and monitoring of ARDS in&#xD;
      a large animal model. PFR has been shown to be elevated prior to the cytokine storm which&#xD;
      classically occurs in ARDS. Early detection of ALI and ARDS is intimately linked to a&#xD;
      patient's chance of survival as early treatment consisting of the preparation for intensive&#xD;
      care, prone positioning and protective mechanical ventilation can be implemented early in the&#xD;
      process. In the present study the investigators aim to use real-time PFR as an early detector&#xD;
      for COVID19-induced ARDS. The investigators will also collect EBPs onto a membrane for&#xD;
      subsequent molecular analysis. Previous studies have shown that most of those proteins found&#xD;
      in bronchoalveolar lavage (BAL) can also be detected in EBPs deposited on membranes. The&#xD;
      investigators therefore also aim to be able to diagnose COVID19 by analyzing EBPs using&#xD;
      Polymerase Chain Reaction (PCR) with the same specificity as PCR from BAL, with the added&#xD;
      benefit of being able to identify protein biomarkers for early detection of ARDS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      EBP will be measured on 100 patients who are coronavirus (COVID-19) positive as indicated by&#xD;
      PCR tests. Measurement will be done on daily basis from the time the patient is admitted to&#xD;
      the hospital as an inpatient until either discharge or transition to ICU care. The initiation&#xD;
      of mechanical ventilation in ICU patients will facilitate the tracking of EBP patterns over&#xD;
      the course of disease in each patient. EBP measurements will also be done on 100 patients&#xD;
      without COVID19 infection who have normal lung function as a control cohort.&#xD;
&#xD;
      The study will involve measurements on patients who have been placed on mechanical&#xD;
      ventilation in the ICU. The purpose of utilizing PFR will be to reduce the need for invasive&#xD;
      diagnostic tests such as bronchoscopy and for hospital transportation associated with tests&#xD;
      such as CT scans. This will ultimately serve to not only decrease the risk of infecting other&#xD;
      patients and staff in the hospital environment, but also to facilitate careful monitoring of&#xD;
      these critical patients by measuring the extent of lung injury over time. In addition to PFR,&#xD;
      EBP will be collected and measured on a daily basis to track the EBP patterns on patients in&#xD;
      mechanical ventilation. Pre-clinical studies have shown that EBP can measure the extent of&#xD;
      lung injury over time (onset of ARDS and recovery (unpublished data))&#xD;
&#xD;
      Measurements are also planned for patients who are on mechanical ventilation on&#xD;
      extracorporeal membrane oxygenation (ECMO) support as well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2024</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>12 Months</target_duration>
  <primary_outcome>
    <measure>Concentration of COVID-19 through PCR testing of EBPs</measure>
    <time_frame>12-36 months</time_frame>
    <description>Real Time-PCR will be used to detect the presence of COVID-19 on membranes on which EBP have been collected to determine the efficacy of using the collection device for non-invasive detection of infection.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Protein concentration in EBP</measure>
    <time_frame>12-36 months</time_frame>
    <description>Proteins will be measured in the samples of EBPs collected on the membrane for the purpose of identifying protein biomarkers of disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Particle flow rate (particles per minute) in exhaled air</measure>
    <time_frame>12-36 months</time_frame>
    <description>The investigators have recently shown that Exhaled Breath Particles (EBP) measured as particle flow rate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR has been shown to increase before the cytokine storm which is a hallmark of ARDS. Early detection of ALI and ARDS is crucial for increasing a patient's chance of survival as it allows for early treatment, such as preparing for intensive care, prone positioning and protective mechanical ventilation settings. In the present study the investigators aim to use real-time PFR as an early detector for COVID-19-induced ARDS.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Covid19</condition>
  <condition>ARDS, Human</condition>
  <condition>ALI</condition>
  <arm_group>
    <arm_group_label>COVID-19 positive</arm_group_label>
    <description>COVID-19-positive patients with pulmonary infection, ALI or ARDS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COVID-19 negative</arm_group_label>
    <description>COVID-19-negative patients with pulmonary infection, ALI or ARDS</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples, broncho alveolar lavage sample, exhaled breath particles&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with pulmonary infection, ALI or ARDS. Patients on mechanical ventilation. Normal&#xD;
        breathing patients. Patients on ECMO support.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of ALI&#xD;
&#xD;
          -  Clinical diagnosis of ARDS&#xD;
&#xD;
          -  COVID-19 infection as measured by a positive PCR test&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Severe neurological disease&#xD;
&#xD;
          -  Drug abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandra Lindstedt Ingemansson, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Region Skåne, Lund University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sandra Lindstedt Ingemansson, MD, PhD</last_name>
    <phone>+46737220580</phone>
    <email>sandra.lindstedt_ingemansson@med.lu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Leif Pierre, PhD</last_name>
    <phone>+467073096605</phone>
    <email>leif.pierre@skane.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Region Skåne</name>
      <address>
        <city>Lund</city>
        <state>Skåne Län</state>
        <zip>22460</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra Lindstedt Ingemansson, MD, PhD</last_name>
      <phone>0737220580</phone>
      <email>sandra.lindstedt_ingemansson@med.lu.se</email>
    </contact>
    <contact_backup>
      <last_name>Leif Pierre, PhD</last_name>
      <phone>+46703096605</phone>
      <email>leif.pierre@skane.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <reference>
    <citation>Broberg E, Andreasson J, Fakhro M, Olin AC, Wagner D, Hyllen S, Lindstedt S. Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients. ERJ Open Res. 2020 Feb 10;6(1):00198-2019. doi: 10.1183/23120541.00198-2019. eCollection 2020 Jan.</citation>
    <PMID>32055633</PMID>
  </reference>
  <reference>
    <citation>Stenlo M, Hyllen S, Silva IAN, Bolukbas DA, Pierre L, Hallgren O, Wagner DE, Lindstedt S. Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2020 Mar 1;318(3):L510-L517. doi: 10.1152/ajplung.00524.2019. Epub 2020 Jan 29.</citation>
    <PMID>31994907</PMID>
  </reference>
  <reference>
    <citation>Broberg E, Hyllen S, Algotsson L, Wagner DE, Lindstedt S. Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction. Exp Clin Transplant. 2019 Dec;17(6):803-812. doi: 10.6002/ect.2019.0187. Epub 2019 Oct 11.</citation>
    <PMID>31615381</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Exhaled Breath Particles</keyword>
  <keyword>Particles in Exhaled Air (PExA)</keyword>
  <keyword>COVID-19</keyword>
  <keyword>ARDS</keyword>
  <keyword>ALI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Lung Injury</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/NCT04503057
org study id: PEx ARDS
nct id: NCT04503057
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Acute Respiratory Distress Syndrome (ARDS) reflects the hallmark of the critical course of
      coronavirus (COVID19). The investigators have recently shown that Exhaled Breath Particles
      (EBP) measured as particle flow rate (PFR) from the airways could be used as a noninvasive
      real-time early detection method for primary graft dysfunction (which bears a
      pathophysiological resemblance to ARDS) in lung transplant patients. The investigators have
      also previously demonstrated the utility of PFR in early detection and monitoring of ARDS in
      a large animal model. PFR has been shown to be elevated prior to the cytokine storm which
      classically occurs in ARDS. Early detection of ALI and ARDS is intimately linked to a
      patient's chance of survival as early treatment consisting of the preparation for intensive
      care, prone positioning and protective mechanical ventilation can be implemented early in the
      process. In the present study the investigators aim to use real-time PFR as an early detector
      for COVID19-induced ARDS. The investigators will also collect EBPs onto a membrane for
      subsequent molecular analysis. Previous studies have shown that most of those proteins found
      in bronchoalveolar lavage (BAL) can also be detected in EBPs deposited on membranes. The
      investigators therefore also aim to be able to diagnose COVID19 by analyzing EBPs using
      Polymerase Chain Reaction (PCR) with the same specificity as PCR from BAL, with the added
      benefit of being able to identify protein biomarkers for early detection of ARDS.
EBP will be measured on 100 patients who are coronavirus (COVID-19) positive as indicated by
      PCR tests. Measurement will be done on daily basis from the time the patient is admitted to
      the hospital as an inpatient until either discharge or transition to ICU care. The initiation
      of mechanical ventilation in ICU patients will facilitate the tracking of EBP patterns over
      the course of disease in each patient. EBP measurements will also be done on 100 patients
      without COVID19 infection who have normal lung function as a control cohort.

      The study will involve measurements on patients who have been placed on mechanical
      ventilation in the ICU. The purpose of utilizing PFR will be to reduce the need for invasive
      diagnostic tests such as bronchoscopy and for hospital transportation associated with tests
      such as CT scans. This will ultimately serve to not only decrease the risk of infecting other
      patients and staff in the hospital environment, but also to facilitate careful monitoring of
      these critical patients by measuring the extent of lung injury over time. In addition to PFR,
      EBP will be collected and measured on a daily basis to track the EBP patterns on patients in
      mechanical ventilation. Pre-clinical studies have shown that EBP can measure the extent of
      lung injury over time (onset of ARDS and recovery (unpublished data))

      Measurements are also planned for patients who are on mechanical ventilation on
      extracorporeal membrane oxygenation (ECMO) support as well.
observational model: Case-Control
time perspective: Prospective
measure: Concentration of COVID-19 through PCR testing of EBPs
time frame: 12-36 months
description: Real Time-PCR will be used to detect the presence of COVID-19 on membranes on which EBP have been collected to determine the efficacy of using the collection device for non-invasive detection of infection.
measure: Protein concentration in EBP
time frame: 12-36 months
description: Proteins will be measured in the samples of EBPs collected on the membrane for the purpose of identifying protein biomarkers of disease.
measure: Particle flow rate (particles per minute) in exhaled air
time frame: 12-36 months
description: The investigators have recently shown that Exhaled Breath Particles (EBP) measured as particle flow rate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR has been shown to increase before the cytokine storm which is a hallmark of ARDS. Early detection of ALI and ARDS is crucial for increasing a patient's chance of survival as it allows for early treatment, such as preparing for intensive care, prone positioning and protective mechanical ventilation settings. In the present study the investigators aim to use real-time PFR as an early detector for COVID-19-induced ARDS.
arm group label: COVID-19 positive
description: COVID-19-positive patients with pulmonary infection, ALI or ARDS
arm group label: COVID-19 negative
description: COVID-19-negative patients with pulmonary infection, ALI or ARDS
Blood samples, broncho alveolar lavage sample, exhaled breath particles
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: 90 Years
healthy volunteers: No
last name: Sandra Lindstedt Ingemansson, MD, PhD
role: Principal Investigator
affiliation: Region Skåne, Lund University
last name: Sandra Lindstedt Ingemansson, MD, PhD
phone: +46737220580
email: sandra.lindstedt_ingemansson@med.lu.se
last name: Leif Pierre, PhD
phone: +467073096605
email: leif.pierre@skane.se
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
citation: Broberg E, Andreasson J, Fakhro M, Olin AC, Wagner D, Hyllen S, Lindstedt S. Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients. ERJ Open Res. 2020 Feb 10;6(1):00198-2019. doi: 10.1183/23120541.00198-2019. eCollection 2020 Jan.
PMID: 32055633
citation: Stenlo M, Hyllen S, Silva IAN, Bolukbas DA, Pierre L, Hallgren O, Wagner DE, Lindstedt S. Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2020 Mar 1;318(3):L510-L517. doi: 10.1152/ajplung.00524.2019. Epub 2020 Jan 29.
PMID: 31994907
citation: Broberg E, Hyllen S, Algotsson L, Wagner DE, Lindstedt S. Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction. Exp Clin Transplant. 2019 Dec;17(6):803-812. doi: 10.6002/ect.2019.0187. Epub 2019 Oct 11.
PMID: 31615381
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Lung Injury
sharing ipd: No