<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/NCT04422626</url>
  </required_header>
  <id_info>
    <org_study_id>20802-5/2020/EÜIG</org_study_id>
    <nct_id>NCT04422626</nct_id>
  </id_info>
  <brief_title>Data Analysis of the Cytokine Adsorption Treatment on Coronavirus Disease-19 (COVID-19) Patients With Respiratory Failure</brief_title>
  <acronym>CYTOAID</acronym>
  <official_title>Data Collection on the Application of Cytokine Adsorption Therapy on Patients With Acute Respiratory Failure Caused by COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pecs</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pecs</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>
      Severe sepsis and septic shock are some of the leading causes of mortality in intensive care&#xD;
      unit (ICU) admitted COVID-19 patients. The main cause of early mortality is the uncontrolled&#xD;
      release of inflammatory mediators leading to cardiovascular failure. CytoSorb, a recently&#xD;
      developed, highly biocompatible hemadsorption device has been tested, which can selectively&#xD;
      remove inflammatory mediators from the circulation. This device is currently commercially&#xD;
      available, and in Europe, it has been approved for clinical use. Based on experience to date,&#xD;
      this adsorption technique may influence the immune function; removing inflammatory mediators&#xD;
      from the blood may improve organ functions and even increase the chances of survival. CYTOAID&#xD;
      is an observational, non-interventional study to assess the effectiveness of early cytokine&#xD;
      adsorption therapy in critically ill patients who have been admitted to the ICU because of&#xD;
      COVID-19 infection. Data on the applied therapy on COVID-19 patients in ICU will be collected&#xD;
      and analyzed. The patient's examination and therapy will be applied according to the current&#xD;
      regulations at the clinics and the current professional standards. The study does not require&#xD;
      any additional examination or intervention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the early phase of sepsis, the activation of innate immunity plays a significant role.&#xD;
      Immune cells enhance the production of pro-inflammatory mediators. These pro-inflammatory&#xD;
      mediators are responsible for the development of immune response and the intensification of&#xD;
      the inflammatory processes. To counteract this, anti-inflammatory mediators limit and&#xD;
      alleviate inflammation. Critically ill septic patients with higher levels of both anti- and&#xD;
      proinflammatory mediators are at higher risk for death. The main cause for early mortality is&#xD;
      the uncontrolled release of inflammatory mediators leading to cardiovascular failure, while&#xD;
      in the late phase of the disease, secondary infections and the subsequent multiorgan failure&#xD;
      dominate due to the exhaustion of the immune functions and the subsequent insufficient&#xD;
      protective mechanisms. Therefore, it has been suggested that the outcomes of severe sepsis&#xD;
      can be improved by attenuating the inflammatory processes. A recently developed, highly&#xD;
      biocompatible hemadsorption device has been tested that can selectively remove inflammatory&#xD;
      mediators from the circulation. This device is currently commercially available, and in&#xD;
      Europe, it has been approved for clinical use. Based on experience to date, this adsorption&#xD;
      technique may influence the immune function; removing inflammatory mediators from the blood&#xD;
      may improve organ functions and even increase the chances of survival.&#xD;
&#xD;
      During the study, data will be collected exclusively; the application of CytoSorb therapy&#xD;
      will be considered by the current physician always on an individual basis. Data will be&#xD;
      recorded during hospitalization (using the documentations of the ICU) and immediately after&#xD;
      discharge.&#xD;
&#xD;
      This study is suitable for recording every step of medical care from the diagnosis of&#xD;
      SARS-CoV-2 infection. To investigate the biomarkers and the genetic background that&#xD;
      potentially play a role in the infection, biological samples will be also collected - by&#xD;
      already indicated interventions during standard care, i.e. without additional intervention.&#xD;
&#xD;
      This study aims to describe cytokine adsorption therapy (CytoSorb) in general and to detect&#xD;
      its most important features. The study would also like to assess the safety and&#xD;
      cost-effectiveness of the therapy, evaluate specific interventions required during the&#xD;
      treatment, and to assess the outcomes of the disease. This study can provide important data&#xD;
      and expand our knowledge about COVID-19 and its treatment, as well as improve the outcomes of&#xD;
      the disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The human resources required to start enrollment were not available anymore.&#xD;
  </why_stopped>
  <start_date type="Anticipated">February 1, 2022</start_date>
  <completion_date type="Anticipated">December 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 1, 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>Change in the partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio after CytoSorb therapy</measure>
    <time_frame>24 months</time_frame>
    <description>Change in the PaO2/FiO2 ratio after CytoSorb therapy as compared to baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in inflammatory biomarker levels during treatment</measure>
    <time_frame>24 months</time_frame>
    <description>Change in white blood cell count and c-reactive protein levels during treatment compared to the baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in organ function</measure>
    <time_frame>24 months</time_frame>
    <description>measured by sequential organ failure assessment (SOFA/sub-SOFA) score during treatment assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of stay in ICU</measure>
    <time_frame>24 months</time_frame>
    <description>given in days, assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of hospital stay</measure>
    <time_frame>24 months</time_frame>
    <description>given in days, assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>24 months</time_frame>
    <description>given in days, assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of vasopressor therapy</measure>
    <time_frame>24 months</time_frame>
    <description>given in days, assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of renal replacement therapy</measure>
    <time_frame>24 months</time_frame>
    <description>given in days, assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of critical illness polyneuropathy and/or myopathy</measure>
    <time_frame>24 months</time_frame>
    <description>assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>need for extracorporeal membrane oxygenation (ECMO)</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients progressing to the need for ECMO assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cost calculation</measure>
    <time_frame>24 months</time_frame>
    <description>The financial demand of the treatment of COVID-19 infection spent on each patient will be calculated by a healthcare economist after the trial is completed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>device-related adverse and serious adverse events</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients with device-related adverse and serious adverse events assessed by the treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients, who died during their hospital stay, assessed by the treating physician</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>SARS-CoV-2</condition>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Critically ill COVID-19 patients, who receive CytoSorb therapy</arm_group_label>
    <description>Patients in ICU due to critical COVID-19 infection, who receive early (within the first 24 hours, but no later than 48 hours after intubation) CytoSorb therapy on consultant's discretion.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Three tubes (less than 25 ml) of blood and 2 ml of saliva will be collected to detect&#xD;
      different antibodies, just in case if the physician already ordered blood test. Additional&#xD;
      puncture won't be carried out.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All adult patients admitted to ICUs requiring mechanical ventilation with proven COVID-19&#xD;
        infection and treated with CytoSorb.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  confirmed COVID-19 infection&#xD;
&#xD;
          -  ICU admission&#xD;
&#xD;
          -  Mechanical ventilation due to COVID-19 pulmonary complications&#xD;
&#xD;
          -  Moderate to severe acute respiratory distress syndrome (ARDS)&#xD;
&#xD;
          -  CytoSorb therapy indicated by the attending medical team preferably within the first&#xD;
             24 hours, but no later than 48 hours after intubation&#xD;
&#xD;
          -  Informed consent for data collection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unlikely survival for 24 hours according to the attending physician&#xD;
&#xD;
          -  Acute onset of hemato-oncological illness&#xD;
&#xD;
          -  Patient already on ECMO&#xD;
&#xD;
          -  Immunosuppression: on chronic systemic steroid therapy (&gt;10 mg prednisolon/day);&#xD;
             immunosuppressive agents (i.e.: methotrexate, azathioprine, cyclosporin, tacrolimus,&#xD;
             cyclophosphamide)&#xD;
&#xD;
          -  Patients with transplanted vital organs&#xD;
&#xD;
          -  Thrombocytopenia (&lt;20,000/uL)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Péter Hegyi, MD, PhD, DSc</last_name>
    <role>Study Chair</role>
    <affiliation>Insitute for Translational Medicine, University of Pécs, HU</affiliation>
  </overall_official>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 6, 2020</study_first_submitted>
  <study_first_submitted_qc>June 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CytoSorb</keyword>
  <keyword>COVID-19</keyword>
  <keyword>acute respiratory failure</keyword>
  <keyword>cytokine</keyword>
  <keyword>Intensive care unit</keyword>
  <keyword>Sars-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Insufficiency</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/NCT04422626
org study id: 20802-5/2020/EÜIG
nct id: NCT04422626
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Severe sepsis and septic shock are some of the leading causes of mortality in intensive care
      unit (ICU) admitted COVID-19 patients. The main cause of early mortality is the uncontrolled
      release of inflammatory mediators leading to cardiovascular failure. CytoSorb, a recently
      developed, highly biocompatible hemadsorption device has been tested, which can selectively
      remove inflammatory mediators from the circulation. This device is currently commercially
      available, and in Europe, it has been approved for clinical use. Based on experience to date,
      this adsorption technique may influence the immune function; removing inflammatory mediators
      from the blood may improve organ functions and even increase the chances of survival. CYTOAID
      is an observational, non-interventional study to assess the effectiveness of early cytokine
      adsorption therapy in critically ill patients who have been admitted to the ICU because of
      COVID-19 infection. Data on the applied therapy on COVID-19 patients in ICU will be collected
      and analyzed. The patient's examination and therapy will be applied according to the current
      regulations at the clinics and the current professional standards. The study does not require
      any additional examination or intervention.
In the early phase of sepsis, the activation of innate immunity plays a significant role.
      Immune cells enhance the production of pro-inflammatory mediators. These pro-inflammatory
      mediators are responsible for the development of immune response and the intensification of
      the inflammatory processes. To counteract this, anti-inflammatory mediators limit and
      alleviate inflammation. Critically ill septic patients with higher levels of both anti- and
      proinflammatory mediators are at higher risk for death. The main cause for early mortality is
      the uncontrolled release of inflammatory mediators leading to cardiovascular failure, while
      in the late phase of the disease, secondary infections and the subsequent multiorgan failure
      dominate due to the exhaustion of the immune functions and the subsequent insufficient
      protective mechanisms. Therefore, it has been suggested that the outcomes of severe sepsis
      can be improved by attenuating the inflammatory processes. A recently developed, highly
      biocompatible hemadsorption device has been tested that can selectively remove inflammatory
      mediators from the circulation. This device is currently commercially available, and in
      Europe, it has been approved for clinical use. Based on experience to date, this adsorption
      technique may influence the immune function; removing inflammatory mediators from the blood
      may improve organ functions and even increase the chances of survival.

      During the study, data will be collected exclusively; the application of CytoSorb therapy
      will be considered by the current physician always on an individual basis. Data will be
      recorded during hospitalization (using the documentations of the ICU) and immediately after
      discharge.

      This study is suitable for recording every step of medical care from the diagnosis of
      SARS-CoV-2 infection. To investigate the biomarkers and the genetic background that
      potentially play a role in the infection, biological samples will be also collected - by
      already indicated interventions during standard care, i.e. without additional intervention.

      This study aims to describe cytokine adsorption therapy (CytoSorb) in general and to detect
      its most important features. The study would also like to assess the safety and
      cost-effectiveness of the therapy, evaluate specific interventions required during the
      treatment, and to assess the outcomes of the disease. This study can provide important data
      and expand our knowledge about COVID-19 and its treatment, as well as improve the outcomes of
      the disease.
observational model: Cohort
time perspective: Prospective
measure: Change in the partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio after CytoSorb therapy
time frame: 24 months
description: Change in the PaO2/FiO2 ratio after CytoSorb therapy as compared to baseline
measure: Change in inflammatory biomarker levels during treatment
time frame: 24 months
description: Change in white blood cell count and c-reactive protein levels during treatment compared to the baseline
measure: change in organ function
time frame: 24 months
description: measured by sequential organ failure assessment (SOFA/sub-SOFA) score during treatment assessed by the treating physician
measure: length of stay in ICU
time frame: 24 months
description: given in days, assessed by the treating physician
measure: length of hospital stay
time frame: 24 months
description: given in days, assessed by the treating physician
measure: Duration of mechanical ventilation
time frame: 24 months
description: given in days, assessed by the treating physician
measure: Duration of vasopressor therapy
time frame: 24 months
description: given in days, assessed by the treating physician
measure: Duration of renal replacement therapy
time frame: 24 months
description: given in days, assessed by the treating physician
measure: Occurrence of critical illness polyneuropathy and/or myopathy
time frame: 24 months
description: assessed by the treating physician
measure: need for extracorporeal membrane oxygenation (ECMO)
time frame: 24 months
description: Number of patients progressing to the need for ECMO assessed by the treating physician
measure: cost calculation
time frame: 24 months
description: The financial demand of the treatment of COVID-19 infection spent on each patient will be calculated by a healthcare economist after the trial is completed.
measure: device-related adverse and serious adverse events
time frame: 24 months
description: Number of patients with device-related adverse and serious adverse events assessed by the treating physician
measure: In-hospital mortality
time frame: 24 months
description: Number of patients, who died during their hospital stay, assessed by the treating physician
arm group label: Critically ill COVID-19 patients, who receive CytoSorb therapy
description: Patients in ICU due to critical COVID-19 infection, who receive early (within the first 24 hours, but no later than 48 hours after intubation) CytoSorb therapy on consultant's discretion.
Three tubes (less than 25 ml) of blood and 2 ml of saliva will be collected to detect
      different antibodies, just in case if the physician already ordered blood test. Additional
      puncture won't be carried out.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Péter Hegyi, MD, PhD, DSc
role: Study Chair
affiliation: Insitute for Translational Medicine, University of Pécs, HU
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Insufficiency
sharing ipd: No