<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/NCT04405544</url>
  </required_header>
  <id_info>
    <org_study_id>NMSC-01-20</org_study_id>
    <nct_id>NCT04405544</nct_id>
  </id_info>
  <brief_title>Determination of Acute Encephalopathy Predictors in Patients With COVID-19</brief_title>
  <official_title>Determination of Acute Encephalopathy Predictors in Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia</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>
      The SARS-CoV-2 infection was detected in December 2019 in Wuhan City, China. The infection&#xD;
      affects all age groups, although childhood is the lowest proportion of those affected.&#xD;
&#xD;
      The main clinical manifestations that require hospitalization of infected patients are SARS&#xD;
      pneumonia, which may require treatment in the intensive care unit (27%) and its progression&#xD;
      into acute respiratory distress syndrome (67%) with life-threatening conditions in almost 25%&#xD;
      of patients diagnosed with &quot;SARS-CoV-2 infection&quot;.&#xD;
&#xD;
      Nervous system damage with SARS-CoV-2 infection has been practically not investigated, but&#xD;
      neurological disorders have been reported in 36% of these patients.&#xD;
&#xD;
      Finally, the mortality rate associated with the new virus is high in patients who require&#xD;
      treatment in intensive care units (62% of cases).&#xD;
&#xD;
      Therefore, we are conducting a prospective study to identify acute encephalopathy predictors&#xD;
      in patients with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, cohort-based, adaptive design study that aims to identify acute&#xD;
      encephalopathy predictors in patients with COVID-19. Patients with community-acquired&#xD;
      pneumonia and confirmed pulmonary tissue infiltration will be enrolled in the study based on&#xD;
      CT data with changes corresponding to the medium and high probability of coronavirus&#xD;
      pneumonia (CO-RADS 4-5) and lesion of at least 25% of one lung.&#xD;
&#xD;
      Each patient will be examined at least twice (2 visits): P1 - on admission to hospital; P2 -&#xD;
      in 10±5 days.&#xD;
&#xD;
      In the further course of the disease patients will be divided into 2 groups (cohorts). Group&#xD;
      1 - patients who have developed acute encephalopathy. Group 2 - patients who at the moment of&#xD;
      discharge have no acute encephalopathy.&#xD;
&#xD;
      The study will collect clinical exam ( including neurological signs), neurophysiological data&#xD;
      (including electroencephalography (EEG) and evoked potential (EP)), comprehensive laboratory&#xD;
      tests, CT-scan and all standards of care to identify predictors of acute encephalopathy.&#xD;
&#xD;
      The study will consist of two phases:&#xD;
&#xD;
        1. The pilot phase - inclusion of the first 60 patients, followed by an interim analysis on&#xD;
           the basis of which will be clarified:&#xD;
&#xD;
             -  sample size;&#xD;
&#xD;
             -  clinical, laboratory and instrumental parameters to be analyzed;&#xD;
&#xD;
             -  terms and frequency of the EEG and EP.&#xD;
&#xD;
        2. The main phase - further patient recruitment and all procedures required by the&#xD;
           protocol.&#xD;
&#xD;
      The intermediate and final analysis will include both patients who have developed acute&#xD;
      encephalopathy (main group) and patients who have not developed acute encephalopathy (control&#xD;
      group).&#xD;
&#xD;
      Acute encephalopathy will be defined as recently stated :&#xD;
&#xD;
        1. The term acute encephalopathy refers to a rapidly developing (over less than 4 weeks,&#xD;
           but usually within hours to a few days) pathobiological process in the brain. This is a&#xD;
           preferred term&#xD;
&#xD;
        2. Acute encephalopathy can lead to a clinical presentation of subsyndromal delirium,&#xD;
           delirium, or in case of a severely decreased level of consciousness, coma; all&#xD;
           representing a change from baseline cognitive status&#xD;
&#xD;
        3. The term delirium refers to a clinical state characterized by a combination of features&#xD;
           defined by diagnostic systems such as the DSM-5.&#xD;
&#xD;
      Delirium according to the DSM-5 is defined if criterium A-E are fulfilled:&#xD;
&#xD;
      A. Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift&#xD;
      attention) and awareness (reduced orientation to the environment).&#xD;
&#xD;
      B. The disturbance develops over a short period of time (usually hours to a few days)&#xD;
      represents a change from baseline attention and awareness, and tends to fluctuate in severity&#xD;
      during the course of the day.&#xD;
&#xD;
      C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language,&#xD;
      visuospatial ability, or perception).&#xD;
&#xD;
      D. The disturbances in criteria A and C are not explained by another pre-existing,&#xD;
      established, or evolving neurocognitive disorder, and do not occur in the context of a&#xD;
      severely reduced level of arousal, such as coma.&#xD;
&#xD;
      E. There is evidence from the history, physical examination, or laboratory findings that the&#xD;
      disturbance is a direct physiologic consequence of another medical condition, substance&#xD;
      intoxication or withdrawal (i.e. because of a drug of abuse medication), or exposure to a&#xD;
      toxin, or is because of multiple etiologies [1].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Actual">October 29, 2020</completion_date>
  <primary_completion_date type="Actual">July 22, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The percentage of patients who have developed encephalopathy</measure>
    <time_frame>10 days</time_frame>
    <description>The percentage of patients who have developed encephalopathy</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Encephalopathy</condition>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Main</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>patients with COVID-19 and Acute Encephalopathy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>patients with COVID-19 without Acute Encephalopathy</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CT-scan</intervention_name>
    <description>chest CT-scan</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Main</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>EEG</intervention_name>
    <description>Electroencephalography</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Main</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>EP</intervention_name>
    <description>Evoked potential</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Main</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pulse oximetry</intervention_name>
    <description>Pulse oximetry</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Main</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood tests</intervention_name>
    <description>Blood tests</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Main</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women aged 18 to 60 years&#xD;
&#xD;
          -  Out-of-hospital pneumonia with confirmed pulmonary tissue infiltration according to CT&#xD;
             with changes corresponding to the average and high probability of coronavirus&#xD;
             pneumonia (4-5 levels by CO-RADS classification) and the loss of more than 25% of one&#xD;
             of the lungs.&#xD;
&#xD;
          -  The patient has read the information sheet and signed the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Negative PCR test for coronavirus infection.&#xD;
&#xD;
          -  The presence in the anamnesis of data for myocardial infarction or stroke.&#xD;
&#xD;
          -  Verified thrombophilia.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Patients with malignant tumors (including anamnesis), including postoperative period&#xD;
             in the background of chemo and/or radiation therapy.&#xD;
&#xD;
          -  Acute stroke.&#xD;
&#xD;
        Dropout Criteria:&#xD;
&#xD;
          -  Patient's refusal to participate further in the study.&#xD;
&#xD;
          -  Negative PCR result for coronavirus infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oleg I Vinogradov, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>N.I. Pirogov National Medical and Surgical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>N.I. Pirogov National Medical and Surgical Center</name>
      <address>
        <city>Moscow</city>
        <zip>105203</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <reference>
    <citation>Slooter AJC, Otte WM, Devlin JW, Arora RC, Bleck TP, Claassen J, Duprey MS, Ely EW, Kaplan PW, Latronico N, Morandi A, Neufeld KJ, Sharshar T, MacLullich AMJ, Stevens RD. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020 May;46(5):1020-1022. doi: 10.1007/s00134-019-05907-4. Epub 2020 Feb 13. No abstract available.</citation>
    <PMID>32055887</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>October 29, 2020</last_update_submitted>
  <last_update_submitted_qc>October 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia</investigator_affiliation>
    <investigator_full_name>Oleg Vinogradov</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</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/NCT04405544
org study id: NMSC-01-20
nct id: NCT04405544
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The SARS-CoV-2 infection was detected in December 2019 in Wuhan City, China. The infection
      affects all age groups, although childhood is the lowest proportion of those affected.

      The main clinical manifestations that require hospitalization of infected patients are SARS
      pneumonia, which may require treatment in the intensive care unit (27%) and its progression
      into acute respiratory distress syndrome (67%) with life-threatening conditions in almost 25%
      of patients diagnosed with "SARS-CoV-2 infection".

      Nervous system damage with SARS-CoV-2 infection has been practically not investigated, but
      neurological disorders have been reported in 36% of these patients.

      Finally, the mortality rate associated with the new virus is high in patients who require
      treatment in intensive care units (62% of cases).

      Therefore, we are conducting a prospective study to identify acute encephalopathy predictors
      in patients with COVID-19.
This is a prospective, cohort-based, adaptive design study that aims to identify acute
      encephalopathy predictors in patients with COVID-19. Patients with community-acquired
      pneumonia and confirmed pulmonary tissue infiltration will be enrolled in the study based on
      CT data with changes corresponding to the medium and high probability of coronavirus
      pneumonia (CO-RADS 4-5) and lesion of at least 25% of one lung.

      Each patient will be examined at least twice (2 visits): P1 - on admission to hospital; P2 -
      in 10±5 days.

      In the further course of the disease patients will be divided into 2 groups (cohorts). Group
      1 - patients who have developed acute encephalopathy. Group 2 - patients who at the moment of
      discharge have no acute encephalopathy.

      The study will collect clinical exam ( including neurological signs), neurophysiological data
      (including electroencephalography (EEG) and evoked potential (EP)), comprehensive laboratory
      tests, CT-scan and all standards of care to identify predictors of acute encephalopathy.

      The study will consist of two phases:

        1. The pilot phase - inclusion of the first 60 patients, followed by an interim analysis on
           the basis of which will be clarified:

             -  sample size;

             -  clinical, laboratory and instrumental parameters to be analyzed;

             -  terms and frequency of the EEG and EP.

        2. The main phase - further patient recruitment and all procedures required by the
           protocol.

      The intermediate and final analysis will include both patients who have developed acute
      encephalopathy (main group) and patients who have not developed acute encephalopathy (control
      group).

      Acute encephalopathy will be defined as recently stated :

        1. The term acute encephalopathy refers to a rapidly developing (over less than 4 weeks,
           but usually within hours to a few days) pathobiological process in the brain. This is a
           preferred term

        2. Acute encephalopathy can lead to a clinical presentation of subsyndromal delirium,
           delirium, or in case of a severely decreased level of consciousness, coma; all
           representing a change from baseline cognitive status

        3. The term delirium refers to a clinical state characterized by a combination of features
           defined by diagnostic systems such as the DSM-5.

      Delirium according to the DSM-5 is defined if criterium A-E are fulfilled:

      A. Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift
      attention) and awareness (reduced orientation to the environment).

      B. The disturbance develops over a short period of time (usually hours to a few days)
      represents a change from baseline attention and awareness, and tends to fluctuate in severity
      during the course of the day.

      C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language,
      visuospatial ability, or perception).

      D. The disturbances in criteria A and C are not explained by another pre-existing,
      established, or evolving neurocognitive disorder, and do not occur in the context of a
      severely reduced level of arousal, such as coma.

      E. There is evidence from the history, physical examination, or laboratory findings that the
      disturbance is a direct physiologic consequence of another medical condition, substance
      intoxication or withdrawal (i.e. because of a drug of abuse medication), or exposure to a
      toxin, or is because of multiple etiologies [1].
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: The percentage of patients who have developed encephalopathy
time frame: 10 days
description: The percentage of patients who have developed encephalopathy
arm group label: Main
arm group type: Other
description: patients with COVID-19 and Acute Encephalopathy
arm group label: Control
arm group type: Other
description: patients with COVID-19 without Acute Encephalopathy
intervention type: Diagnostic Test
intervention name: CT-scan
description: chest CT-scan
arm group label: Control
arm group label: Main
intervention type: Diagnostic Test
intervention name: EEG
description: Electroencephalography
arm group label: Control
arm group label: Main
intervention type: Diagnostic Test
intervention name: EP
description: Evoked potential
arm group label: Control
arm group label: Main
intervention type: Diagnostic Test
intervention name: Pulse oximetry
description: Pulse oximetry
arm group label: Control
arm group label: Main
intervention type: Diagnostic Test
intervention name: Blood tests
description: Blood tests
arm group label: Control
arm group label: Main
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Oleg I Vinogradov, MD, PhD
role: Principal Investigator
affiliation: N.I. Pirogov National Medical and Surgical Center
facility: 
country: Russian Federation
citation: Slooter AJC, Otte WM, Devlin JW, Arora RC, Bleck TP, Claassen J, Duprey MS, Ely EW, Kaplan PW, Latronico N, Morandi A, Neufeld KJ, Sharshar T, MacLullich AMJ, Stevens RD. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020 May;46(5):1020-1022. doi: 10.1007/s00134-019-05907-4. Epub 2020 Feb 13. No abstract available.
PMID: 32055887
responsible party type: Principal Investigator
investigator affiliation: State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia
investigator full name: Oleg Vinogradov
investigator title: MD, PhD
mesh term: Brain Diseases
sharing ipd: No