<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/NCT04416100</url>
  </required_header>
  <id_info>
    <org_study_id>20200429-2255</org_study_id>
    <nct_id>NCT04416100</nct_id>
  </id_info>
  <brief_title>Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (COVID-19)</brief_title>
  <acronym>CovILD</acronym>
  <official_title>Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University Innsbruck</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University Innsbruck</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, currently poses&#xD;
      a global economic, social, political and medical challenge. The virus originated in December&#xD;
      2019 in Wuhan, China, and has spread rapidly around the world. Currently, European countries,&#xD;
      including Austria, are severely affected.The most common computed tomographic changes in&#xD;
      acute lung injury include bilateral and subpleural milk glass opacity, consolidation in lower&#xD;
      lobes, or both. In the intermediate phase of the infection (4-14 days after the onset of&#xD;
      symptoms) a so-called &quot;crazy paving&quot; may occur. The most prominent radiological changes occur&#xD;
      around day 10, followed by gradual resolution, which begins two weeks after the onset of&#xD;
      symptoms.&#xD;
&#xD;
      Given the phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, the similar clinical&#xD;
      course in severe cases and overlapping CT patterns in the acute setting, persistent&#xD;
      radiological and pulmonary functional changes in survivors are conceivable. It is also&#xD;
      conceivable that a proportion of survivors will develop progressive ILD, either due to viral&#xD;
      or ventilator-induced alveolar damage, or both.&#xD;
&#xD;
      Here, the investigators intend to investigate COVID-19 survivors through clinical&#xD;
      examinations, functional lung examinations, HR-CT scans, and by determining the&#xD;
      &quot;immunofibrotic&quot; pattern in peripheral mononuclear cells (PBMCs) 1, 3, and 6 months after&#xD;
      discharge.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, currently poses&#xD;
      a global economic, social, political and medical challenge. The virus originated in December&#xD;
      2019 in Wuhan, China, and has spread rapidly around the world. Currently, European countries,&#xD;
      including Austria, are severely affected. In January 2020, the World Health Organisation&#xD;
      declared a &quot;Public Health Event of International Concern&quot; and since 11 March 2020 COVID-19&#xD;
      has been classified as a pandemic. Overall mortality rates vary widely, ranging from 0.5 to&#xD;
      7%. These highly depend on the stringency of the tests in a particular region and the age of&#xD;
      the patients with higher mortality rates in older people. The majority of patients show only&#xD;
      mild symptoms with fever and/or cough, and it is even believed that there is a significant&#xD;
      proportion of untested asymptomatic carriers that can transmit the virus to other people. 26&#xD;
      to 33% of in-patients have been admitted to intensive care due to a severe lung disease. Of&#xD;
      these, 2.5 to 10% required invasive mechanical ventilation and 15 to 22% of these patients&#xD;
      died in hospital, indicating the potential risk to public health. As a result, the current&#xD;
      global death toll from COVID-19 already exceeds 37,000 people on 31 March 2020.&#xD;
&#xD;
      In the SARS-CoV-1 outbreak of 2003, clinical course was characterized by fever, myalgia and&#xD;
      other systemic symptoms, which generally improved after a few days, followed by a second&#xD;
      phase with recurrence of fever, oxygen saturation and imaging progression of pneumonia,&#xD;
      similar to that experienced by severely affected patients in the current pandemic.&#xD;
      Importantly, a significant number of patients infected with SARS-CoV-1 suffered acute&#xD;
      respiratory failure (ARDS) requiring invasive ventilatory support. The pulmonary pathology of&#xD;
      fatal SARS cases was dominated by diffuse alveolar damage (DAD), epithelial cell&#xD;
      proliferation, an increase in macrophages in the lung and extensive consolidation, but&#xD;
      features of bronchiolitis obliterans and organizing pneumonia were also noted. In addition,&#xD;
      survivors of severe SARS-CoV-1 infection showed significant functional and radiological&#xD;
      changes in the lungs even 6 months after infection.&#xD;
&#xD;
      In the current SARS-CoV-2 pandemic, the most common computed tomographic changes in acute&#xD;
      lung injury include bilateral and subpleural milk glass opacity, consolidation in lower&#xD;
      lobes, or both. In the intermediate phase of the infection (4-14 days after the onset of&#xD;
      symptoms) a so-called &quot;crazy paving&quot; may occur. The most prominent radiological changes occur&#xD;
      around day 10, followed by gradual resolution, which begins two weeks after the onset of&#xD;
      symptoms.&#xD;
&#xD;
      Given the phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, the similar clinical&#xD;
      course in severe cases and overlapping CT patterns in the acute setting, persistent&#xD;
      radiological and pulmonary functional changes in survivors are conceivable. It is also&#xD;
      conceivable that a proportion of survivors will develop progressive ILD, either due to viral&#xD;
      or ventilator-induced alveolar damage, or both.&#xD;
&#xD;
      Here, the investigators intend to investigate COVID-19 survivors through clinical&#xD;
      examinations, functional lung examinations, HR-CT scans, and by determining the&#xD;
      &quot;immunofibrotic&quot; pattern in peripheral mononuclear cells (PBMCs) 1, 3, and 6 months after&#xD;
      discharge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 29, 2020</start_date>
  <completion_date type="Anticipated">April 28, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 28, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 1 month after discharge or diagnosis of COVID-19 disease by the use of HR-CT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 3 months after discharge or diagnosis of COVID-19 disease by the use of HR-CT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 6 months after discharge or diagnosis of COVID-19 disease by the use of HR-CT</description>
  </primary_outcome>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Covid-19</condition>
  <condition>Pulmonary Fibrosis</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pulmonary function tests</intervention_name>
    <description>Spirometry or plethysmography, measurement of diffusion capacity</description>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Imaging</intervention_name>
    <description>HRCT and echocardiography as scheduled within routine clinical examinations</description>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>Standard laboratory test as part of routine clinical examination and collection of peripheral blood for immunofibrotic phenotyping</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Collection of peripheral blood will be done in the context of a routine blood draw in all&#xD;
      study participants (in addition for immunofibrotic phenotyping) at our study centre at&#xD;
      indicated time-points.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        COVID-19 patients discharged from hospital or outpatients referred to our Outpatient&#xD;
        Department of Pneumology at the University Hospital of Innsbruck because of persistent&#xD;
        respiratory symptoms in recovery phase will be followed up. Diagnosis of COVID-19 must have&#xD;
        been ensured by nasopharyngeal and oropharyngeal swabs.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female and male patients ≥ 18 years.&#xD;
&#xD;
          -  Confirmed infection with SARS-CoV-2 according to the definition of the Austrian&#xD;
             Federal Ministry of Social Affairs, Health, Care and Consumer Protection&#xD;
&#xD;
          -  Signed and dated declaration of consent by the patient according to ICH-GCP&#xD;
             Guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female and male patients &lt; 18 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Declaration of consent by the patient according to ICH-GCP Guidelines not signed&#xD;
&#xD;
          -  Incapacitated patients&#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>Ivan Tancevski, Doz. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University Innsbruck, Department Internal Medicine II</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Judith Löffler-Ragg, Prof. Dr.</last_name>
    <phone>+43-512-504-81413</phone>
    <email>judith.loeffler@i-med.ac.at</email>
  </overall_contact>
  <location>
    <facility>
      <name>Medical University of Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Judith Löffler-Ragg, Prof. Dr.</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>November 30, 2020</last_update_submitted>
  <last_update_submitted_qc>November 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2020</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>COVID-19</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</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/NCT04416100
org study id: 20200429-2255
nct id: NCT04416100
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, currently poses
      a global economic, social, political and medical challenge. The virus originated in December
      2019 in Wuhan, China, and has spread rapidly around the world. Currently, European countries,
      including Austria, are severely affected.The most common computed tomographic changes in
      acute lung injury include bilateral and subpleural milk glass opacity, consolidation in lower
      lobes, or both. In the intermediate phase of the infection (4-14 days after the onset of
      symptoms) a so-called "crazy paving" may occur. The most prominent radiological changes occur
      around day 10, followed by gradual resolution, which begins two weeks after the onset of
      symptoms.

      Given the phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, the similar clinical
      course in severe cases and overlapping CT patterns in the acute setting, persistent
      radiological and pulmonary functional changes in survivors are conceivable. It is also
      conceivable that a proportion of survivors will develop progressive ILD, either due to viral
      or ventilator-induced alveolar damage, or both.

      Here, the investigators intend to investigate COVID-19 survivors through clinical
      examinations, functional lung examinations, HR-CT scans, and by determining the
      "immunofibrotic" pattern in peripheral mononuclear cells (PBMCs) 1, 3, and 6 months after
      discharge.
COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, currently poses
      a global economic, social, political and medical challenge. The virus originated in December
      2019 in Wuhan, China, and has spread rapidly around the world. Currently, European countries,
      including Austria, are severely affected. In January 2020, the World Health Organisation
      declared a "Public Health Event of International Concern" and since 11 March 2020 COVID-19
      has been classified as a pandemic. Overall mortality rates vary widely, ranging from 0.5 to
      7%. These highly depend on the stringency of the tests in a particular region and the age of
      the patients with higher mortality rates in older people. The majority of patients show only
      mild symptoms with fever and/or cough, and it is even believed that there is a significant
      proportion of untested asymptomatic carriers that can transmit the virus to other people. 26
      to 33% of in-patients have been admitted to intensive care due to a severe lung disease. Of
      these, 2.5 to 10% required invasive mechanical ventilation and 15 to 22% of these patients
      died in hospital, indicating the potential risk to public health. As a result, the current
      global death toll from COVID-19 already exceeds 37,000 people on 31 March 2020.

      In the SARS-CoV-1 outbreak of 2003, clinical course was characterized by fever, myalgia and
      other systemic symptoms, which generally improved after a few days, followed by a second
      phase with recurrence of fever, oxygen saturation and imaging progression of pneumonia,
      similar to that experienced by severely affected patients in the current pandemic.
      Importantly, a significant number of patients infected with SARS-CoV-1 suffered acute
      respiratory failure (ARDS) requiring invasive ventilatory support. The pulmonary pathology of
      fatal SARS cases was dominated by diffuse alveolar damage (DAD), epithelial cell
      proliferation, an increase in macrophages in the lung and extensive consolidation, but
      features of bronchiolitis obliterans and organizing pneumonia were also noted. In addition,
      survivors of severe SARS-CoV-1 infection showed significant functional and radiological
      changes in the lungs even 6 months after infection.

      In the current SARS-CoV-2 pandemic, the most common computed tomographic changes in acute
      lung injury include bilateral and subpleural milk glass opacity, consolidation in lower
      lobes, or both. In the intermediate phase of the infection (4-14 days after the onset of
      symptoms) a so-called "crazy paving" may occur. The most prominent radiological changes occur
      around day 10, followed by gradual resolution, which begins two weeks after the onset of
      symptoms.

      Given the phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, the similar clinical
      course in severe cases and overlapping CT patterns in the acute setting, persistent
      radiological and pulmonary functional changes in survivors are conceivable. It is also
      conceivable that a proportion of survivors will develop progressive ILD, either due to viral
      or ventilator-induced alveolar damage, or both.

      Here, the investigators intend to investigate COVID-19 survivors through clinical
      examinations, functional lung examinations, HR-CT scans, and by determining the
      "immunofibrotic" pattern in peripheral mononuclear cells (PBMCs) 1, 3, and 6 months after
      discharge.
observational model: Cohort
time perspective: Prospective
measure: Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 1 month
time frame: 1 month
description: Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 1 month after discharge or diagnosis of COVID-19 disease by the use of HR-CT.
measure: Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 3 months
time frame: 3 months
description: Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 3 months after discharge or diagnosis of COVID-19 disease by the use of HR-CT
measure: Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 6 months
time frame: 6 months
description: Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 6 months after discharge or diagnosis of COVID-19 disease by the use of HR-CT
intervention type: Diagnostic Test
intervention name: Pulmonary function tests
description: Spirometry or plethysmography, measurement of diffusion capacity
intervention type: Diagnostic Test
intervention name: Imaging
description: HRCT and echocardiography as scheduled within routine clinical examinations
intervention type: Biological
intervention name: Blood sampling
description: Standard laboratory test as part of routine clinical examination and collection of peripheral blood for immunofibrotic phenotyping
Collection of peripheral blood will be done in the context of a routine blood draw in all
      study participants (in addition for immunofibrotic phenotyping) at our study centre at
      indicated time-points.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ivan Tancevski, Doz. Dr.
role: Principal Investigator
affiliation: Medical University Innsbruck, Department Internal Medicine II
last name: Judith Löffler-Ragg, Prof. Dr.
phone: +43-512-504-81413
email: judith.loeffler@i-med.ac.at
facility: 
status: Recruiting
contact: 
country: Austria
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Lung Diseases
mesh term: Pulmonary Fibrosis
mesh term: Lung Diseases, Interstitial
sharing ipd: No