<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/NCT04453527</url>
  </required_header>
  <id_info>
    <org_study_id>PHT/2020/37</org_study_id>
    <nct_id>NCT04453527</nct_id>
  </id_info>
  <brief_title>The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Covid-19</brief_title>
  <official_title>The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Coronavirus Disease 2019</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Portsmouth Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Akari Therapuetics</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Portsmouth Hospitals NHS Trust</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>
      COVID-19 is a new disease and therefore it is still not clear exactly how the virus affects&#xD;
      the body and why people are affected so differently. It causes infection in the lungs and the&#xD;
      virus can then attack blood vessels in the lungs and other organs to spark off an&#xD;
      inflammatory process that can make a person very ill. It also can cause damage within tiny&#xD;
      blood vessels that makes a person's blood thicken up and stop flow in vital organs. The&#xD;
      investigators believe complement (which is a chemical in the body which can be harmful in&#xD;
      excess) orchestrates the inflammation and thickening of the blood that can make a person&#xD;
      sick. The investigators now need to know which of these complement chemicals are elevated in&#xD;
      COVID-19 and compare to healthy volunteers, and assess whether the levels are higher in&#xD;
      people with severe lung disease. The investigators believe that if levels are increased there&#xD;
      are special treatments that can counteract them and potentially be an effective treatment for&#xD;
      COVID-19.&#xD;
&#xD;
      In this study the investigators will measure different parts of the inflammation process to&#xD;
      better understand what may be causing severe disease and to see if there may be benefits from&#xD;
      a new treatment to reduce inflammation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an observational cross-sectional and cohort study to assess whether there is&#xD;
      evidence of increased complement activation and/or LTB4 levels and other parameters of&#xD;
      inflammation and a pro-coagulative state in adult patients hospitalised with COVID-19&#xD;
      compared to healthy controls and also whether these measures differ with increasing severity&#xD;
      of respiratory failure.&#xD;
&#xD;
      Blood samples (serum and plasma) will be obtained from each participant at the time of&#xD;
      recruitment into the trial, to assess the profile of complement activation, cytokines/&#xD;
      chemokines, leukotrienes (specifically leukotriene B4) and markers of coagulation and&#xD;
      inflammation in patients with COVID-19.&#xD;
&#xD;
      Participants within the cohort study will be recruited at the point of admission or as close&#xD;
      to it as possible. Baseline sampling will be performed at time of recruitment. There will be&#xD;
      up to 2 additional sampling points (with not more than one sample per day) if there is any&#xD;
      worsening of the participants respiratory failure (i.e. deteriorating from mild to moderate&#xD;
      or moderate to severe disease).&#xD;
&#xD;
      Patients just admitted to hospital will be asked to consent for both the case control and the&#xD;
      cohort study&#xD;
&#xD;
      Data will be collected at baseline for all participants and then again at each further&#xD;
      sampling point for the participants within the cohort study.&#xD;
&#xD;
      Patient status will be measured at 14 days from the last point of sampling.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 28, 2020</start_date>
  <completion_date type="Actual">May 30, 2021</completion_date>
  <primary_completion_date type="Actual">May 30, 2021</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>Complement Activation</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>C5a, C5, C3, sC5b9, Bb concentration from serum</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Leukotrienes Measure</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>LTB4 concentration from plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Coagulation Measure</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>Level of platelets, INR, APTS, D-Dimer, Fibrinogen, thrombin antithrombin complex (TAT), from citrate plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hyperinflammation Measure</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>• CRP, Ferritin, PCT, LDH, Troponin, ALT from plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cell Count</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>Total White Blood Cell count (including lymphocytes, monocytes and neutrophils)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cytokines and Chemokine Measure</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>Level of • Pro-inflammatory - IL-1α, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-17, GCSF, GMCSF, IFN γ, IP10, MCP-1, MIP1α, TNFα and anti inflammatory IL-4, IL-10, IL-13, IL-22, TGF-α from plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Endothelial dysfunction measures:</measure>
    <time_frame>14 days sampling time period</time_frame>
    <description>VEGF, tissue factor and PAI-1, from plasma</description>
  </primary_outcome>
  <enrollment type="Actual">72</enrollment>
  <condition>Coronavirus</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants with Covid 19 and Healthy Volunteers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - 1. Adults ≥18 years old requiring hospital admission for COVID-19&#xD;
&#xD;
        2. COVID-19 confirmed by either*:&#xD;
&#xD;
          -  A positive swab (using RT-PCR)&#xD;
&#xD;
          -  OR based on a high level of clinical probability confirmed by the presence of typical&#xD;
             symptoms and compatible radiological findings on imaging with no alternative cause for&#xD;
             these findings identified by the treating physician.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Renal replacement therapy on ITU&#xD;
&#xD;
             2. Significant trauma (including an acute fracture or significant head injury)&#xD;
&#xD;
             3. Massive transfusion of blood products&#xD;
&#xD;
             4. Confirmed bacteraemia with pathogenic organism on blood cultures or other severe&#xD;
             bacterial infections (including abscess/empyema) which persist despite broad-spectrum&#xD;
             antibiotics and are thought to be significantly contributing to the patient's symptoms&#xD;
             and clinical state. Recruitment will not be delayed however pending a negative&#xD;
             culture.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Portsmouth Hospitals NHS Trust</name>
      <address>
        <city>Portsmouth</city>
        <zip>PO6 3LY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 25, 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>April 6, 2023</last_update_submitted>
  <last_update_submitted_qc>April 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</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>Coronavirus Infections</mesh_term>
    <mesh_term>Inflammation</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/NCT04453527
org study id: PHT/2020/37
nct id: NCT04453527
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
COVID-19 is a new disease and therefore it is still not clear exactly how the virus affects
      the body and why people are affected so differently. It causes infection in the lungs and the
      virus can then attack blood vessels in the lungs and other organs to spark off an
      inflammatory process that can make a person very ill. It also can cause damage within tiny
      blood vessels that makes a person's blood thicken up and stop flow in vital organs. The
      investigators believe complement (which is a chemical in the body which can be harmful in
      excess) orchestrates the inflammation and thickening of the blood that can make a person
      sick. The investigators now need to know which of these complement chemicals are elevated in
      COVID-19 and compare to healthy volunteers, and assess whether the levels are higher in
      people with severe lung disease. The investigators believe that if levels are increased there
      are special treatments that can counteract them and potentially be an effective treatment for
      COVID-19.

      In this study the investigators will measure different parts of the inflammation process to
      better understand what may be causing severe disease and to see if there may be benefits from
      a new treatment to reduce inflammation
This study is an observational cross-sectional and cohort study to assess whether there is
      evidence of increased complement activation and/or LTB4 levels and other parameters of
      inflammation and a pro-coagulative state in adult patients hospitalised with COVID-19
      compared to healthy controls and also whether these measures differ with increasing severity
      of respiratory failure.

      Blood samples (serum and plasma) will be obtained from each participant at the time of
      recruitment into the trial, to assess the profile of complement activation, cytokines/
      chemokines, leukotrienes (specifically leukotriene B4) and markers of coagulation and
      inflammation in patients with COVID-19.

      Participants within the cohort study will be recruited at the point of admission or as close
      to it as possible. Baseline sampling will be performed at time of recruitment. There will be
      up to 2 additional sampling points (with not more than one sample per day) if there is any
      worsening of the participants respiratory failure (i.e. deteriorating from mild to moderate
      or moderate to severe disease).

      Patients just admitted to hospital will be asked to consent for both the case control and the
      cohort study

      Data will be collected at baseline for all participants and then again at each further
      sampling point for the participants within the cohort study.

      Patient status will be measured at 14 days from the last point of sampling.
observational model: Cohort
time perspective: Prospective
measure: Complement Activation
time frame: 14 days sampling time period
description: C5a, C5, C3, sC5b9, Bb concentration from serum
measure: Leukotrienes Measure
time frame: 14 days sampling time period
description: LTB4 concentration from plasma
measure: Coagulation Measure
time frame: 14 days sampling time period
description: Level of platelets, INR, APTS, D-Dimer, Fibrinogen, thrombin antithrombin complex (TAT), from citrate plasma
measure: Hyperinflammation Measure
time frame: 14 days sampling time period
description: • CRP, Ferritin, PCT, LDH, Troponin, ALT from plasma
measure: Cell Count
time frame: 14 days sampling time period
description: Total White Blood Cell count (including lymphocytes, monocytes and neutrophils)
measure: Cytokines and Chemokine Measure
time frame: 14 days sampling time period
description: Level of • Pro-inflammatory - IL-1α, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-17, GCSF, GMCSF, IFN γ, IP10, MCP-1, MIP1α, TNFα and anti inflammatory IL-4, IL-10, IL-13, IL-22, TGF-α from plasma
measure: Endothelial dysfunction measures:
time frame: 14 days sampling time period
description: VEGF, tissue factor and PAI-1, from plasma
Blood sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Coronavirus Infections
mesh term: Inflammation
sharing ipd: No