<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/NCT02188992</url>
  </required_header>
  <id_info>
    <org_study_id>2013/0267</org_study_id>
    <nct_id>NCT02188992</nct_id>
  </id_info>
  <brief_title>Early PREdiction of Severe Sepsis I (ExPRES-Sepsis I) Study</brief_title>
  <acronym>ExPRES</acronym>
  <official_title>Early Prediction of Severe Sepsis (ExPRESSepsis) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Technology Strategy Board, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Becton, Dickinson and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Edinburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Between 6 and 16% of patients presenting to hospital emergency departments have infections,&#xD;
      with half of these having signs of systemic inflammation (known as 'sepsis'). A second issue&#xD;
      is that, at time of presentation, it can be difficult to determine who has inflammation as a&#xD;
      result of infection and who does not.&#xD;
&#xD;
      Some of the patients with infections will deteriorate to organ failure ('severe sepsis')&#xD;
      including failure of the heart and blood vessels to maintain normal blood pressure ('septic&#xD;
      shock'). Septic shock as arguably the most dangerous form of severe sepsis is associated with&#xD;
      a significant mortality, which can be reduced by early intervention. However identifying&#xD;
      those patients who are at high risk of deteriorating to septic shock can be difficult on&#xD;
      initial presentation to hospital, and thus these patients risk being 'triaged' to an&#xD;
      inappropriate level of care and/or missing the crucial early interventions which can modify&#xD;
      mortality. Equally failure to identify which patients have underlying infections can lead to&#xD;
      potential inappropriate targeting of antibiotics. Existing clinical and laboratory tests are&#xD;
      often unable to accurately identify those patients with infection, and those who are likely&#xD;
      to deteriorate to severe sepsis and septic shock.&#xD;
&#xD;
      Investigators in this group have recently identified several signatures of immune system&#xD;
      activation which predict those patients who are likely to deteriorate, and which patients&#xD;
      with suspected infection subsequently have this confirmed. Such tests would have major&#xD;
      benefits for the management of patients with early suspected infection and sepsis if they can&#xD;
      be translated into a test usable in everyday clinical practice. This study aims to determine&#xD;
      the prevalence of these markers in a cohort of patients admitted with suspected sepsis, and&#xD;
      their predictive ability for developing established septic shock. From this investigators aim&#xD;
      to derive an optimal test, to be tested in a validation cohort (ExPRES-Sepsis II) which will&#xD;
      be suitable for everyday clinical practice, and thus take the next step towards developing a&#xD;
      market-ready test.&#xD;
&#xD;
      Study hypothesis is:&#xD;
&#xD;
      Measurement of markers of immune activation will allow i) Risk stratification for&#xD;
      deterioration into severe sepsis ii) Risk stratification for death amongst patients&#xD;
      presenting with sepsis iii) Identification of patients with confirmed sepsis&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</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>Development of septic shock</measure>
    <time_frame>Within first 72 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Confirmation of suspected infection</measure>
    <time_frame>within first 72 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospital outcome (lived/died)</measure>
    <time_frame>Within first 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to septic shock onset</measure>
    <time_frame>Within the first 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death from sepsis</measure>
    <time_frame>Within first 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ dysfunction, total and individual organs as determined by SOFA score</measure>
    <time_frame>within first 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>subsequent admission to critical care</measure>
    <time_frame>within first 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in immune activation in those patients who develop any of the events mention in previous outcomes (i.e. septic shock, death, organ dysfunction, admission to critical care)</measure>
    <time_frame>within first 72 hours</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">401</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <description>Patients with sepsis syndrome, without criteria for severe sepsis/septic shock. These patients are recruited from the emergency department.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <description>Patients with community acquired sepsis syndrome REQUIRING critical care admission due to severity of sepsis. These patients are recruited from the critical care areas (ICU/HDU).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <description>Patients without sepsis syndrome. Age and gender matched to cohort 1, and recruited from Emergency Department.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Samples of serum and plasma will be stored frozen.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients in the initial 12 hours following presentation to hospital with suspected sepsis,&#xD;
        i.e. patients with signs of systemic inflammation (i.e. meeting criteria for SIRS) where&#xD;
        the treating clinician takes microbial samples and/or starts empiric antibiotics.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;16 (&gt;18 in England)&#xD;
&#xD;
          -  SIRS criteria met (2 or more of White Cell Count (WCC) &gt;11 or &lt;4, Heart Rate (HR) &gt;90,&#xD;
             Respiratory Rate (RR) &gt;20 or temp &gt;38 or &lt;36oC)&#xD;
&#xD;
          -  Clinical suspicion of sepsis (cultures taken or antibiotics started)&#xD;
&#xD;
          -  Enrolled within 12 hours of hospital admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute pancreatitis&#xD;
&#xD;
          -  Septic shock at time of enrolment&#xD;
&#xD;
          -  Severe organ failure at time of enrolment (immediate requirement for ventilation,&#xD;
             vasopressor or renal replacement therapy)&#xD;
&#xD;
          -  Haematological malignancy&#xD;
&#xD;
          -  Recent chemotherapy (past 2 weeks)&#xD;
&#xD;
          -  Myelodysplastic syndromes&#xD;
&#xD;
          -  Known neutropaenia&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Blood transfusion &gt;4 units in past week&#xD;
&#xD;
          -  Oral Corticosteroids for &gt;24 hours prior to enrolment&#xD;
&#xD;
          -  Decision not for active therapy/ palliative care at admission&#xD;
&#xD;
          -  Lacking in capacity to consent and nearest relative/welfare guardian not available for&#xD;
             consultation and proxy consent (Scotland only)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim S Walsh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NHS Lothian/University of Edinburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Wright, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Newcastle-upon-Tyne Hospitals NHS Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Manu Shankar-Hari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guy's and St Thomas' NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andrew Conway Morris, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Simpson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Newcastle University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alasdair Gray, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NHS Lothian/University of Edinburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Infirmary of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH16 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Thomas' Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Infirmary</name>
      <address>
        <city>Newcastle</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>October 25, 2016</last_update_submitted>
  <last_update_submitted_qc>October 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 26, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>Immune activation</keyword>
  <keyword>Systemic Inflammation</keyword>
  <keyword>Emergency Medicine</keyword>
  <keyword>Critical Care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</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/NCT02188992
org study id: 2013/0267
nct id: NCT02188992
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Between 6 and 16% of patients presenting to hospital emergency departments have infections,
      with half of these having signs of systemic inflammation (known as 'sepsis'). A second issue
      is that, at time of presentation, it can be difficult to determine who has inflammation as a
      result of infection and who does not.

      Some of the patients with infections will deteriorate to organ failure ('severe sepsis')
      including failure of the heart and blood vessels to maintain normal blood pressure ('septic
      shock'). Septic shock as arguably the most dangerous form of severe sepsis is associated with
      a significant mortality, which can be reduced by early intervention. However identifying
      those patients who are at high risk of deteriorating to septic shock can be difficult on
      initial presentation to hospital, and thus these patients risk being 'triaged' to an
      inappropriate level of care and/or missing the crucial early interventions which can modify
      mortality. Equally failure to identify which patients have underlying infections can lead to
      potential inappropriate targeting of antibiotics. Existing clinical and laboratory tests are
      often unable to accurately identify those patients with infection, and those who are likely
      to deteriorate to severe sepsis and septic shock.

      Investigators in this group have recently identified several signatures of immune system
      activation which predict those patients who are likely to deteriorate, and which patients
      with suspected infection subsequently have this confirmed. Such tests would have major
      benefits for the management of patients with early suspected infection and sepsis if they can
      be translated into a test usable in everyday clinical practice. This study aims to determine
      the prevalence of these markers in a cohort of patients admitted with suspected sepsis, and
      their predictive ability for developing established septic shock. From this investigators aim
      to derive an optimal test, to be tested in a validation cohort (ExPRES-Sepsis II) which will
      be suitable for everyday clinical practice, and thus take the next step towards developing a
      market-ready test.

      Study hypothesis is:

      Measurement of markers of immune activation will allow i) Risk stratification for
      deterioration into severe sepsis ii) Risk stratification for death amongst patients
      presenting with sepsis iii) Identification of patients with confirmed sepsis
observational model: Cohort
time perspective: Prospective
measure: Development of septic shock
time frame: Within first 72 hours
measure: Confirmation of suspected infection
time frame: within first 72 hours
measure: Hospital outcome (lived/died)
time frame: Within first 72 hours
measure: Time to septic shock onset
time frame: Within the first 72 hours
measure: Death from sepsis
time frame: Within first 72 hours
measure: Organ dysfunction, total and individual organs as determined by SOFA score
time frame: within first 72 hours
measure: subsequent admission to critical care
time frame: within first 72 hours
measure: Changes in immune activation in those patients who develop any of the events mention in previous outcomes (i.e. septic shock, death, organ dysfunction, admission to critical care)
time frame: within first 72 hours
arm group label: Cohort 1
description: Patients with sepsis syndrome, without criteria for severe sepsis/septic shock. These patients are recruited from the emergency department.
arm group label: Cohort 2
description: Patients with community acquired sepsis syndrome REQUIRING critical care admission due to severity of sepsis. These patients are recruited from the critical care areas (ICU/HDU).
arm group label: Cohort 3
description: Patients without sepsis syndrome. Age and gender matched to cohort 1, and recruited from Emergency Department.
Samples of serum and plasma will be stored frozen.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Tim S Walsh, MD
role: Principal Investigator
affiliation: NHS Lothian/University of Edinburgh
last name: John Wright, MD
role: Principal Investigator
affiliation: Newcastle-upon-Tyne Hospitals NHS Trust
last name: Manu Shankar-Hari, MD
role: Principal Investigator
affiliation: Guy's and St Thomas' NHS Foundation Trust
last name: Andrew Conway Morris, MD
role: Principal Investigator
affiliation: University of Cambridge
last name: John Simpson, MD
role: Principal Investigator
affiliation: Newcastle University
last name: Alasdair Gray, MD
role: Principal Investigator
affiliation: NHS Lothian/University of Edinburgh
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia