<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/NCT03818269</url>
  </required_header>
  <id_info>
    <org_study_id>DARGENT 2018</org_study_id>
    <nct_id>NCT03818269</nct_id>
  </id_info>
  <brief_title>Study of Subcutaneous Interstitial Pressure During Sepsis</brief_title>
  <acronym>PISEP</acronym>
  <official_title>Study of Subcutaneous Interstitial Pressure During Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire Dijon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire Dijon</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The pathophysiology of sepsis is characterized by the sudden onset of vasodilation and&#xD;
      vascular permeability with capillary leakage. This leakage contributes to the development of&#xD;
      generalized edema which is not clinically detectable below 4 litres but which becomes visible&#xD;
      after a few days. The edema accumulates mainly at the subcutaneous level due to the high&#xD;
      compliance of this tissue. Edema, and therefore hydrosodium overload, testifies to the&#xD;
      severity of the inflammation. However, it could also be harmful in itself (affecting&#xD;
      microcirculation and increasing mortality) as suggested by numerous clinical and experimental&#xD;
      studies.&#xD;
&#xD;
      The transfer of fluids between vascular and interstitial compartments during sepsis therefore&#xD;
      has a central role in the pathophysiology of the disease and associated mortality. These&#xD;
      transfers are mainly controlled at the microvascular level (with constant permeability) by&#xD;
      the difference between capillary (CP) and interstitial (IP) pressures. In healthy subjects,&#xD;
      subcutaneous IP is discreetly negative (-1 mmHg) and varies very little. On the other hand, a&#xD;
      sometimes drastic decrease in IP has been described in various localized and systemic&#xD;
      inflammatory situations. These pressure variations may be explained by the collagen structure&#xD;
      of the interstitial tissue and a change in the three-dimensional conformation of these&#xD;
      macromolecules induced by inflammation mediators. In an animal model of sepsis, a study&#xD;
      showed significantly lower pressure in a group of animals in endotoxic shock. IP has never&#xD;
      been measured in humans during sepsis. The objective of this study is to analyze subcutaneous&#xD;
      IP (SCIP) in patients with septic shock compared with controls in order to evaluate the&#xD;
      direct role of interstitial tissue in the onset of edema during sepsis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 26, 2019</start_date>
  <completion_date type="Actual">August 9, 2022</completion_date>
  <primary_completion_date type="Actual">July 21, 2022</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Value of Initial subcutaneous interstitial pressure</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure the difference between the subcutaneous interstitial pressure of patients in septic shock compared to patients without sepsis</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Patients With Septic Shock</condition>
  <arm_group>
    <arm_group_label>Septic shock</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Subcutaneous pressure measurement</intervention_name>
    <description>Subcutaneous interstitial measurement at D1 and D2</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Septic shock</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Criteria common to both groups:&#xD;
&#xD;
          -  Adult,&#xD;
&#xD;
          -  Admitted within the last 24 hours in intensive care,&#xD;
&#xD;
          -  Under mechanical ventilation with orotracheal intubation,&#xD;
&#xD;
          -  Without clinically detectable edema (in any area)&#xD;
&#xD;
          -  Patient and/or guardian and/or close relative has given written consent&#xD;
&#xD;
        Patients included in the &quot;septic shock&quot; arm:&#xD;
&#xD;
          -  Diagnosis of septic shock as defined by the &quot;Sepsis-3&quot; Consensus Conference (JAMA&#xD;
             2016) (34): documented or highly suspected infection with SOFA ≥ 2, persistent&#xD;
             hypotension after correction of hypovolemia requiring vasopressor administration, and&#xD;
             serum lactate &gt; 2 mmol/l.&#xD;
&#xD;
          -  Vascular filling &lt; 50 ml/kg&#xD;
&#xD;
        Patients included in the control arm:&#xD;
&#xD;
          -  Absence of sepsis and shock from any cause:&#xD;
&#xD;
               -  PAS &gt; 100 mmHg&#xD;
&#xD;
               -  Absence of vasopressors&#xD;
&#xD;
               -  Preserved urine &gt; 0.5 ml/kg/h&#xD;
&#xD;
               -  Normal serum lactate&#xD;
&#xD;
          -  Crystalloid infusions &lt; 50ml/kg over the previous 12 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  not affiliated to national health insurance&#xD;
&#xD;
          -  under court protection&#xD;
&#xD;
          -  pregnant or breastfeeding&#xD;
&#xD;
          -  Clinical disseminated intravascular coagulation (DIC) with hemorrhagic syndrome&#xD;
&#xD;
          -  Admitted after resuscitation for cardiac arrest&#xD;
&#xD;
          -  Presenting cardiogenic shock&#xD;
&#xD;
          -  Presenting acute pancreatitis&#xD;
&#xD;
          -  Severe overall dehydration (clinical signs of dehydration and natremia &gt; 150mmol/l)&#xD;
&#xD;
          -  Presenting metformin intoxication&#xD;
&#xD;
          -  In severe sepsis or septic shock for more than 24 hours,&#xD;
&#xD;
          -  Dying or for whom death seems imminent (within 24 hours),&#xD;
&#xD;
          -  Hypersensitivity to lidocaine and/or prilocaine or local anesthetics of the amide type&#xD;
             or to any of the excipients of EMLAPATCH®&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CHU de DIJON</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCL - Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>November 29, 2022</last_update_submitted>
  <last_update_submitted_qc>November 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2022</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>Shock, Septic</mesh_term>
  </condition_browse>
  <!-- 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/NCT03818269
org study id: DARGENT 2018
nct id: NCT03818269
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The pathophysiology of sepsis is characterized by the sudden onset of vasodilation and
      vascular permeability with capillary leakage. This leakage contributes to the development of
      generalized edema which is not clinically detectable below 4 litres but which becomes visible
      after a few days. The edema accumulates mainly at the subcutaneous level due to the high
      compliance of this tissue. Edema, and therefore hydrosodium overload, testifies to the
      severity of the inflammation. However, it could also be harmful in itself (affecting
      microcirculation and increasing mortality) as suggested by numerous clinical and experimental
      studies.

      The transfer of fluids between vascular and interstitial compartments during sepsis therefore
      has a central role in the pathophysiology of the disease and associated mortality. These
      transfers are mainly controlled at the microvascular level (with constant permeability) by
      the difference between capillary (CP) and interstitial (IP) pressures. In healthy subjects,
      subcutaneous IP is discreetly negative (-1 mmHg) and varies very little. On the other hand, a
      sometimes drastic decrease in IP has been described in various localized and systemic
      inflammatory situations. These pressure variations may be explained by the collagen structure
      of the interstitial tissue and a change in the three-dimensional conformation of these
      macromolecules induced by inflammation mediators. In an animal model of sepsis, a study
      showed significantly lower pressure in a group of animals in endotoxic shock. IP has never
      been measured in humans during sepsis. The objective of this study is to analyze subcutaneous
      IP (SCIP) in patients with septic shock compared with controls in order to evaluate the
      direct role of interstitial tissue in the onset of edema during sepsis.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Value of Initial subcutaneous interstitial pressure
time frame: Day 0
description: Measure the difference between the subcutaneous interstitial pressure of patients in septic shock compared to patients without sepsis
arm group label: Septic shock
arm group type: Other
arm group label: Control
arm group type: Other
intervention type: Procedure
intervention name: Subcutaneous pressure measurement
description: Subcutaneous interstitial measurement at D1 and D2
arm group label: Control
arm group label: Septic shock
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Shock, Septic