<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/NCT04453670</url>
  </required_header>
  <id_info>
    <org_study_id>Obs2020</org_study_id>
    <nct_id>NCT04453670</nct_id>
  </id_info>
  <brief_title>Neuropathology in Adults Intensive Care Unit Patients With COVID 19</brief_title>
  <official_title>A Prospective Observational Autopsy Study of Neuropathology in Adults Intensive Care Unit Patients With COVID 19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Versailles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Versailles</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>
      This is a single center observational autopsy study, conducted during the first wave of the&#xD;
      coronavirus disease (COVID-19) pandemic in France. The main objective is to evaluate brain&#xD;
      damages in patients who died from COVID-19 to inform the cause of death. Investigations&#xD;
      include macroscopic and histology examinations, and virology analyses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Setting: academic center designed as a referral center for patients with COVID-19 Design:&#xD;
      single center observational autopsy study Participants: intensive care unit (ICU) adults who&#xD;
      died from confirmed COVID-19 during the first wave of the pandemic in France.&#xD;
&#xD;
      Oversight: As per legal health authority requirement only patients with suspected or&#xD;
      confirmed severe acute respiratory syndrome (SARS)- related to coronavirus 2 infection were&#xD;
      admitted to the ICU. The department of pathology and forensic medicine is allowed by legal&#xD;
      authority to perform autopsy of non-survivors from COVID-19 to inform the cause of death as&#xD;
      per ministerial decree of July 12 2017 and March 28, 2020. In this context, of autopsy for&#xD;
      medical purpose and public interest there is no requirement for institutional review board&#xD;
      submission. However, consent from patients legal representative or closest relatives is&#xD;
      required for autopsy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 10, 2020</start_date>
  <completion_date type="Actual">May 15, 2020</completion_date>
  <primary_completion_date type="Actual">May 11, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>detection of severe acute respiratory syndrome related to coronavirus-2 in brain tissues</measure>
    <time_frame>From death up to five days</time_frame>
    <description>Specimens treatments Genome detection by real-time reverse transcriptase-polymerase chain reaction and viral culture Next generation sequencing Specimen RNA pre-treatment and evaluation MinION sequencing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>quantification of inflammation, necrosis and hemorrhage in different brain areas</measure>
    <time_frame>From death up to five days</time_frame>
    <description>The left hemisphere will be fixed in 10% buffered formalin. Multiple fresh samples will be acquired from different areas of the right hemisphere for freezing. For each frozen sample, a mirror sample of formalin-fixed paraffin-embedded tissue will be taken from the left hemisphere. Samples were fixed with 3.6% glutaraldehyde and embedded in plastic for electron microscopy. Paraffin sections cut to 3-µm thickness will be stained with hematoxylin and eosin stain. Immunohistochemistry will be performed with Clusters of Differentiation 3,4, 20, 68, 138, and glial fibrillary acid protein antibodies on automated immunostainer. Slides will be scanned and analyzed. Electron microscopy will be performed and images will be acquired.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">7</enrollment>
  <condition>COVID 19</condition>
  <arm_group>
    <arm_group_label>COVID-19 non-survivors</arm_group_label>
    <description>ICU adults who died from severe COVID-19 and in whom autopsy could be performed</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>autopsy</intervention_name>
    <description>autopsy</description>
    <arm_group_label>COVID-19 non-survivors</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      plasma cerebrospinal fluid brain parenchyma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive patients admitted to the ICU for severe COVID-19 and who died during their&#xD;
        ICU stay and for whom family consent was obtained for performing autopsy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults&#xD;
&#xD;
          -  admitted to the ICU&#xD;
&#xD;
          -  confirmed COVID-19&#xD;
&#xD;
          -  died during ICU stay&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  refusal from patient's legal representative or closest relative&#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>djillali annane</last_name>
    <role>Study Chair</role>
    <affiliation>University Versailles SQY Unversité Paris Saclay</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Raymond Poincaré</name>
      <address>
        <city>Garches</city>
        <zip>92380</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>June 30, 2020</last_update_submitted>
  <last_update_submitted_qc>June 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Versailles</investigator_affiliation>
    <investigator_full_name>Djillali Annane</investigator_full_name>
    <investigator_title>Professor in intensive care medicine</investigator_title>
  </responsible_party>
  <keyword>autopsy</keyword>
  <keyword>coronavirus</keyword>
  <keyword>brain</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>all individual patient data will be available upon request to the study official and after signing a data sharing agreement immediately after publication in a peer-reviewed journal</ipd_description>
  </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/NCT04453670
org study id: Obs2020
nct id: NCT04453670
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a single center observational autopsy study, conducted during the first wave of the
      coronavirus disease (COVID-19) pandemic in France. The main objective is to evaluate brain
      damages in patients who died from COVID-19 to inform the cause of death. Investigations
      include macroscopic and histology examinations, and virology analyses.
Setting: academic center designed as a referral center for patients with COVID-19 Design:
      single center observational autopsy study Participants: intensive care unit (ICU) adults who
      died from confirmed COVID-19 during the first wave of the pandemic in France.

      Oversight: As per legal health authority requirement only patients with suspected or
      confirmed severe acute respiratory syndrome (SARS)- related to coronavirus 2 infection were
      admitted to the ICU. The department of pathology and forensic medicine is allowed by legal
      authority to perform autopsy of non-survivors from COVID-19 to inform the cause of death as
      per ministerial decree of July 12 2017 and March 28, 2020. In this context, of autopsy for
      medical purpose and public interest there is no requirement for institutional review board
      submission. However, consent from patients legal representative or closest relatives is
      required for autopsy.
observational model: Case-Only
time perspective: Prospective
measure: detection of severe acute respiratory syndrome related to coronavirus-2 in brain tissues
time frame: From death up to five days
description: Specimens treatments Genome detection by real-time reverse transcriptase-polymerase chain reaction and viral culture Next generation sequencing Specimen RNA pre-treatment and evaluation MinION sequencing
measure: quantification of inflammation, necrosis and hemorrhage in different brain areas
time frame: From death up to five days
description: The left hemisphere will be fixed in 10% buffered formalin. Multiple fresh samples will be acquired from different areas of the right hemisphere for freezing. For each frozen sample, a mirror sample of formalin-fixed paraffin-embedded tissue will be taken from the left hemisphere. Samples were fixed with 3.6% glutaraldehyde and embedded in plastic for electron microscopy. Paraffin sections cut to 3-µm thickness will be stained with hematoxylin and eosin stain. Immunohistochemistry will be performed with Clusters of Differentiation 3,4, 20, 68, 138, and glial fibrillary acid protein antibodies on automated immunostainer. Slides will be scanned and analyzed. Electron microscopy will be performed and images will be acquired.
arm group label: COVID-19 non-survivors
description: ICU adults who died from severe COVID-19 and in whom autopsy could be performed
intervention type: Procedure
intervention name: autopsy
description: autopsy
arm group label: COVID-19 non-survivors
plasma cerebrospinal fluid brain parenchyma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: djillali annane
role: Study Chair
affiliation: University Versailles SQY Unversité Paris Saclay
facility: 
country: France
responsible party type: Principal Investigator
investigator affiliation: University of Versailles
investigator full name: Djillali Annane
investigator title: Professor in intensive care medicine
mesh term: COVID-19
sharing ipd: Undecided
ipd description: all individual patient data will be available upon request to the study official and after signing a data sharing agreement immediately after publication in a peer-reviewed journal