<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/NCT03788772</url>
  </required_header>
  <id_info>
    <org_study_id>APHP180016</org_study_id>
    <secondary_id>2018-A01934-51</secondary_id>
    <nct_id>NCT03788772</nct_id>
  </id_info>
  <brief_title>Systems Analysis of Antigen Presenting Cells in Human Sepsis</brief_title>
  <acronym>DENDRISEPSIS</acronym>
  <official_title>Systems Analysis of Antigen Presenting Cells in Human Sepsis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      Sepsis is a common life-threatening inflammatory response to infection and is the leading&#xD;
      cause of death in the intensive care unit. Septic patients exhibit a complex&#xD;
      immunosuppressive response affecting both innate and adaptive components of immunity, with a&#xD;
      possible link to nosocomial infections. However, the molecular and cellular mechanisms&#xD;
      resulting in secondary immunosuppression remain poorly understood, but may involve the&#xD;
      antigen-presenting cells (APC, including dendritic cells and monocytes/macrophages) that link&#xD;
      innate and adaptive immunity. Furthermore, the increasing phenotypic and functional&#xD;
      heterogeneity of APC subsets raise the question of their respective role in sepsis. We&#xD;
      propose to address the pathophysiologal role of APC using systems biology approaches in human&#xD;
      sepsis.&#xD;
&#xD;
      The objective is to go from low- to high-resolution analysis of APC subset diversity and&#xD;
      underlying molecular and functional features in sepsis. The global objective will be reached&#xD;
      through:&#xD;
&#xD;
        1. Systematic description and phenotypic analysis of circulating APC subsets in sepsis&#xD;
&#xD;
        2. Association of APC subsets distribution, phenotype and function with severe sepsis&#xD;
           physiopathology and relevant clinical outcomes (ICU-acquired infections and death)&#xD;
&#xD;
        3. High-resolution molecular profiling of circulating APC subsets using population level&#xD;
           and single cell RNAseq.&#xD;
&#xD;
      To this aim, the investigator designed a prospective interventional study in order to collect&#xD;
      blood samples at significant time points in patients with sepsis or septic shock (the&#xD;
      population of interest) and relevant control subjects, either critically ill patients with&#xD;
      non-septic acute circulatory failure or age-matched healthy subjects. The study's&#xD;
      intervention is limited to additional blood samples. The risks and constraints are related to&#xD;
      additional blood samples (maximum 120mL), which will be performed either from an arterial&#xD;
      catheter when present in ICU patients, or from a venous puncture for patients without&#xD;
      arterial catheters and for healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 15, 2019</start_date>
  <completion_date type="Anticipated">July 15, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 15, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ICU-acquired infections (nosocomial infections)</measure>
    <time_frame>up to 3 months after the inclusion</time_frame>
    <description>Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-hospital death</measure>
    <time_frame>up to 3 months after the inclusion</time_frame>
    <description>date of death</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Sepsis</condition>
  <condition>Acute Circulatory Failure</condition>
  <arm_group>
    <arm_group_label>Adults patients hospitalized in ICU</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adult patients hospitalized in the intensive care unit (ICU) for severe infections (sepsis and septic shock) or or non-septic shock (cardiogenic or hemorrhagic shock)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Multiple blood sampling</intervention_name>
    <description>ICU septic and non-septic patients will be subjected to repeated blood samples at the following time-points: ICU admission, day 4/5, ICU and hospital discharge, 3 months. Patients exhibiting ICU-acquired infection will also be sampled at the time of diagnosis (up to 6 additional blood samples of 20 mL within 3 months = 120mL)</description>
    <arm_group_label>Adults patients hospitalized in ICU</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Simple blood sampling</intervention_name>
    <description>Healthy controls (blood donors and patients undergoing elective cataract surgery) will be subjected to one single blood sample of 20 mL.</description>
    <arm_group_label>Adults patients hospitalized in ICU</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ICU patients with severe infections (Sepsis-3 definitions):&#xD;
&#xD;
             clinically or microbiologically documented infection and organ dysfunction graded as&#xD;
             follows:&#xD;
&#xD;
               -  Sepsis: increase in the Sequential Organ Failure Assessment (SOFA) score of 2&#xD;
                  points or more.&#xD;
&#xD;
               -  Septic shock: vasopressor requirement to maintain a mean arterial pressure ≥&#xD;
                  65mmHg and serum lactate level &gt; 2 mmol/L in the absence of hypovolemia&#xD;
&#xD;
          2. ICU patients with non-septic acute circulatory failure:&#xD;
&#xD;
               -  Cardiogenic shock: left ventricle systolic dysfunction (echocardiographic left&#xD;
                  ventricular ejection fraction &lt; 45%) and the need of vasopressor (norepinephrine&#xD;
                  at any dose and inotropic support (dobutamine ≥ 5 µg/kg/min or epinephrine at any&#xD;
                  dose) in the absence of patent infection.&#xD;
&#xD;
               -  Severe hemorrhage: hypotension with acute blood loss requiring transfusion of at&#xD;
                  least four packed red cells within 24h and vasopressor support by norepinephrine&#xD;
                  or epinephrine at any dose.&#xD;
&#xD;
          3. Healthy controls:&#xD;
&#xD;
               -  Blood donors&#xD;
&#xD;
               -  Patients undergoing elective cataract surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. All ICU patients&#xD;
&#xD;
               -  hematological malignancy (or significant history of bone marrow disease),&#xD;
&#xD;
               -  HIV infection at any stage,&#xD;
&#xD;
               -  any immunosuppressive drugs including corticosteroids ≥ 0.5 mg/kg equivalent&#xD;
                  prednisone per day for more 7 days,&#xD;
&#xD;
               -  anticancer chemotherapy or chemotherapy received during the last three months&#xD;
                  before inclusion&#xD;
&#xD;
               -  bone marrow or solid organ transplantation,&#xD;
&#xD;
               -  leucopenia (&lt;1000/mm3) excepted if due to sepsis,&#xD;
&#xD;
               -  pregnancy&#xD;
&#xD;
               -  do-not-resuscitate order at ICU admission&#xD;
&#xD;
               -  patients under legal protection regimen.&#xD;
&#xD;
          2. Healthy controls&#xD;
&#xD;
               -  history of inflammatory disease&#xD;
&#xD;
               -  hematological malignancy (or significant history of bone marrow disease),&#xD;
&#xD;
               -  HIV infection at any stage,&#xD;
&#xD;
               -  any immunosuppressive drugs including corticosteroids ≥ 0.5 mg/kg equivalent&#xD;
                  prednisone per day for more 7 days,&#xD;
&#xD;
               -  anticancer chemotherapy or immunotherapy received during the last three months&#xD;
                  before inclusion&#xD;
&#xD;
               -  bone marrow or solid organ transplantation,&#xD;
&#xD;
               -  pregnancy&#xD;
&#xD;
               -  infectious symptoms within the previous month&#xD;
&#xD;
               -  subjects under legal protection regimen&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frédéric PENE, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vassili SOUMELIS, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Frédéric PENE, MD PhD</last_name>
    <phone>+33 1 58 41 46 77</phone>
    <email>frederic.pene@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cochin Hospital, AP-HP</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frédéric PENE, MD PhD</last_name>
      <phone>+33 1 58 41 46 77</phone>
      <email>frederic.pene@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>December 2, 2019</last_update_submitted>
  <last_update_submitted_qc>December 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dendritic cell</keyword>
  <keyword>sepsis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Shock</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/NCT03788772
org study id: APHP180016
secondary id: 2018-A01934-51
nct id: NCT03788772
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Sepsis is a common life-threatening inflammatory response to infection and is the leading
      cause of death in the intensive care unit. Septic patients exhibit a complex
      immunosuppressive response affecting both innate and adaptive components of immunity, with a
      possible link to nosocomial infections. However, the molecular and cellular mechanisms
      resulting in secondary immunosuppression remain poorly understood, but may involve the
      antigen-presenting cells (APC, including dendritic cells and monocytes/macrophages) that link
      innate and adaptive immunity. Furthermore, the increasing phenotypic and functional
      heterogeneity of APC subsets raise the question of their respective role in sepsis. We
      propose to address the pathophysiologal role of APC using systems biology approaches in human
      sepsis.

      The objective is to go from low- to high-resolution analysis of APC subset diversity and
      underlying molecular and functional features in sepsis. The global objective will be reached
      through:

        1. Systematic description and phenotypic analysis of circulating APC subsets in sepsis

        2. Association of APC subsets distribution, phenotype and function with severe sepsis
           physiopathology and relevant clinical outcomes (ICU-acquired infections and death)

        3. High-resolution molecular profiling of circulating APC subsets using population level
           and single cell RNAseq.

      To this aim, the investigator designed a prospective interventional study in order to collect
      blood samples at significant time points in patients with sepsis or septic shock (the
      population of interest) and relevant control subjects, either critically ill patients with
      non-septic acute circulatory failure or age-matched healthy subjects. The study's
      intervention is limited to additional blood samples. The risks and constraints are related to
      additional blood samples (maximum 120mL), which will be performed either from an arterial
      catheter when present in ICU patients, or from a venous puncture for patients without
      arterial catheters and for healthy volunteers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: ICU-acquired infections (nosocomial infections)
time frame: up to 3 months after the inclusion
description: Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU
measure: In-hospital death
time frame: up to 3 months after the inclusion
description: date of death
arm group label: Adults patients hospitalized in ICU
arm group type: Experimental
description: Adult patients hospitalized in the intensive care unit (ICU) for severe infections (sepsis and septic shock) or or non-septic shock (cardiogenic or hemorrhagic shock)
intervention type: Other
intervention name: Multiple blood sampling
description: ICU septic and non-septic patients will be subjected to repeated blood samples at the following time-points: ICU admission, day 4/5, ICU and hospital discharge, 3 months. Patients exhibiting ICU-acquired infection will also be sampled at the time of diagnosis (up to 6 additional blood samples of 20 mL within 3 months = 120mL)
arm group label: Adults patients hospitalized in ICU
intervention type: Other
intervention name: Simple blood sampling
description: Healthy controls (blood donors and patients undergoing elective cataract surgery) will be subjected to one single blood sample of 20 mL.
arm group label: Adults patients hospitalized in ICU
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Frédéric PENE, MD PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Vassili SOUMELIS, MD PhD
role: Study Director
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Frédéric PENE, MD PhD
phone: +33 1 58 41 46 77
email: frederic.pene@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Shock
sharing ipd: No