<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/NCT03306186</url>
  </required_header>
  <id_info>
    <org_study_id>INTELLIGENCE1</org_study_id>
    <nct_id>NCT03306186</nct_id>
  </id_info>
  <brief_title>Hemospec Device for the Diagnosis of Sepsis</brief_title>
  <acronym>INTELLIGENCE-1</acronym>
  <official_title>Integration of Clinical and Laboratory Information to Generate Technological Advance for the Diagnosis of Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ippokration General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tzanion General Hospital of Piraeus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aghia Olga Konstantopouleion General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Athens</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>
      A diagnostic devise, namely HemoSpec, had been developed that integrates clinical&#xD;
      information, along with information on circulating protein biomarkers and the morphology of&#xD;
      white blood cells to achieve early diagnosis of sepsis. The current study is aiming to&#xD;
      validate and improve performance of HemoSpec for the rapid assessment of the critically ill&#xD;
      patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sepsis is a life-threating organ dysfunction resulting from the dysregulated response of the&#xD;
      host to an infection. It is estimated that 1.5 million people present with sepsis annually in&#xD;
      Northern America and another 1.5 million people in Europe; 30 to 50% of them die making&#xD;
      sepsis the leading cause of death. The key-point in the management of sepsis is the early&#xD;
      resuscitation with broad-spectrum antimicrobials and intravenous fluids, if possible within&#xD;
      the first hour. The great mortality of sepsis indicates that this goal is not easy to be&#xD;
      achieved for two main reasons: the first is the delay in recognition of the septic patients&#xD;
      and the second is the resistance of the implicated pathogen to broad-spectrum antimicrobials.&#xD;
&#xD;
      In an attempt to improve the failure of physicians for early sepsis recognition, several&#xD;
      markers have been developed. Some of them rely on clinical signs of the host and others on&#xD;
      the measurements of circulating biomarkers. Recently, qSOFA (quick SOFA score) has been&#xD;
      introduced to help the early recognition of sepsis in patients who present with infection&#xD;
      outside the Intensive care Unit (ICU) i.e. either in the community or during hospitalization&#xD;
      in the general ward1. However, there are concerns of the sensitivity of qSOFA and many&#xD;
      introduce the need to measure biomarkers in serum. These biomarkers are usually protein&#xD;
      molecules that are over-produced in the host as a result of the interaction with an infective&#xD;
      insult. However, these protein molecules are produced by white blood cells. What is currently&#xD;
      known is that although most of patients present with a similar phenotype, their&#xD;
      pathophysiology is diverse. More precisely, although the majority of patients with sepsis&#xD;
      present with high concentrations of protein molecules like interleukin (IL)-6, C-reactive&#xD;
      protein (CRP) and procalcitonin (PCT) in their blood, in some patients circulating white&#xD;
      blood cells remain over-active and in other patients they are significantly anergic, a&#xD;
      situation often known as sepsis-induced immunoparalysis. Another molecule, called soluble&#xD;
      urokinase plasminogen activator receptor (suPAR), is the shed uPAR receptor on neutrophils&#xD;
      and is released in the circulation as a result of neutrophil activation; concentrations&#xD;
      greater than 12 ng/ml can trace with negative predictive value almost 95% the patient at&#xD;
      great chance of unfavorable outcome. As such, the robust diagnosis of sepsis may rely on a&#xD;
      combination of clinical assessment, measurement of protein biomarkers and validation of the&#xD;
      activity of circulating white blood cells.&#xD;
&#xD;
      One FrameWork 7-funded initiative from seven European countries aims to develop a rapid score&#xD;
      that can integrate all clinical and laboratory information and provide early diagnosis&#xD;
      whether a patient has sepsis or not. The vision of this initiative is to build a device that&#xD;
      is called HemoSpec. With this approach, whole blood coming from patients will be in parallel&#xD;
      analyzed into three aspects: a) absolute white blood cell counting; b) information on the&#xD;
      fluidity and activity of the white blood cells using Raman spectroscopy; and c) measurement&#xD;
      of serum levels of IL-6, CRP, PCT and suPAR. The end result is building a diagnostic&#xD;
      algorithm where clinical information is also taken into consideration.&#xD;
&#xD;
      The project was started in November 2013 and the HemoSpec device is anticipated to be ready&#xD;
      by February 2017. The diagnostic performance of HemoSpec is currently based on preliminary&#xD;
      data coming from 60 patients (20 controls, 20 with systemic inflammatory response syndrome&#xD;
      and 20 with sepsis) hospitalized in Jena University Hospital. The current study is aiming to&#xD;
      validate and improve performance of HemoSpec for the rapid assessment of the critically ill&#xD;
      patient in a larger phase II diagnostic study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 9, 2017</start_date>
  <completion_date type="Actual">March 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 30, 2017</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensitivity of HemoSpec for the diagnosis of sepsis</measure>
    <time_frame>3 days</time_frame>
    <description>The sensitivity of HemoSpec output to diagnose the presence of sepsis compared to the absence of sepsis. HemoSpec output will be considered to provide a satisfactory diagnosis of sepsis if sensitivity for the diagnosis is greater than 85%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic performance for sepsis</measure>
    <time_frame>3 days</time_frame>
    <description>The diagnostic performance of HemoSpec output to diagnose the presence of sepsis compared to the absence of sepsis. The diagnostic performance is composed by the aggregation of specificity, positive predictive value and negative predictive value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognostics performance for sepsis</measure>
    <time_frame>28 days</time_frame>
    <description>The prognostic performance of HemoSpec output to predict unfavorable outcome compared to survivors. The prognostic performance is composed by the aggregation of sensitivity, specificity, positive predictive value and negative predictive value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognostic performance for organ dysfunction</measure>
    <time_frame>28 days</time_frame>
    <description>The prognostic performance of HemoSpec output to predict progression into organ dysfunction. The prognostic performance is composed by the aggregation of sensitivity, specificity, positive predictive value and negative predictive value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic performance over qSOFA</measure>
    <time_frame>3 days</time_frame>
    <description>The aggregation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HemoSpec output to indicate patients with infection among those scoring positive for qSOFA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic performance and microbiology</measure>
    <time_frame>3 days</time_frame>
    <description>The diagnostic performance of HemoSpec output to diagnose the presence of sepsis between patients with microbiologically-proven infection and patients without microbiologically-proven infection. The diagnostic performance is composed by the aggregation of sensitivity, specificity, positive predictive value and negative predictive value.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">183</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>HemoSpec</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Diagnosis of sepsis using HemoSpec device</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>HemoSpec</intervention_name>
    <description>Blood sampling for analysis</description>
    <arm_group_label>HemoSpec</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age above or equal to 18 years old&#xD;
&#xD;
          -  Both genders&#xD;
&#xD;
          -  Written consent provided from patients or their first-degree relatives for patients&#xD;
             unable to consent&#xD;
&#xD;
          -  Patients with acute pancreatitis or post-operative or with clinical signs of infection&#xD;
&#xD;
          -  Considerable risk of death as as indicated by the presence of at least one of the&#xD;
             following: i) sudden alteration of mental status; ii) systolic blood pressure less&#xD;
             than 100 mmHg; and iii) high respiratory rate defined as more than or equal to 22&#xD;
             breaths per minute.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known infection by the human immunodeficiency virus-1;&#xD;
&#xD;
          -  Neutropenia defined as an absolute neutrophil count lower than 1000 neutrophils/mm3&#xD;
             due to reasons other than an infection.&#xD;
&#xD;
          -  Single trauma or multiple injuries&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Evangelos J Giamarellos-Bourboulis, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>National and Kapodistrian University of Athens</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Konstantinos Toutouzas, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National and Kapodistrian University of Athens</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Athanasios Prekates, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tzaneion General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stylianos Karatzas, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ippokration General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christos Mathas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aghia Olga General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>1st Department of Propedeutic Surgery, Ippokration General Hospital</name>
      <address>
        <city>Athens</city>
        <zip>11521</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intensive Care Unit, Ippokration General Hospital</name>
      <address>
        <city>Athens</city>
        <zip>11521</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>4th Department of Internal Medicine, ATTIKON University Hospital</name>
      <address>
        <city>Athens</city>
        <zip>12462</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intensive Care Unit, Aghia Olga Konstantopouleion General Hospital</name>
      <address>
        <city>Athens</city>
        <zip>14232</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intensive Care Unit, Tzanio Hospital of Piraeus</name>
      <address>
        <city>Piraeus</city>
        <zip>18536</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <reference>
    <citation>Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.</citation>
    <PMID>26903338</PMID>
  </reference>
  <reference>
    <citation>Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008 Mar;36(3):941-52. doi: 10.1097/CCM.0B013E318165BABB.</citation>
    <PMID>18431284</PMID>
  </reference>
  <reference>
    <citation>Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, Savva A, Tsangaris I, Dimopoulou I, Mouktaroudi M, Raftogiannis M, Georgitsi M, Linner A, Adamis G, Antonopoulou A, Apostolidou E, Chrisofos M, Katsenos C, Koutelidakis I, Kotzampassi K, Koratzanis G, Koupetori M, Kritselis I, Lymberopoulou K, Mandragos K, Marioli A, Sunden-Cullberg J, Mega A, Prekates A, Routsi C, Gogos C, Treutiger CJ, Armaganidis A, Dimopoulos G. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care. 2012 Aug 8;16(4):R149. doi: 10.1186/cc11463.</citation>
    <PMID>22873681</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <last_update_submitted>May 14, 2018</last_update_submitted>
  <last_update_submitted_qc>May 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Athens</investigator_affiliation>
    <investigator_full_name>Evangelos J. Giamarellos-Bourboulis, M.D.</investigator_full_name>
    <investigator_title>Associate Professor of Internal Medicine</investigator_title>
  </responsible_party>
  <keyword>diagnosis</keyword>
  <keyword>prognosis</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>
  <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/NCT03306186
org study id: INTELLIGENCE1
nct id: NCT03306186
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A diagnostic devise, namely HemoSpec, had been developed that integrates clinical
      information, along with information on circulating protein biomarkers and the morphology of
      white blood cells to achieve early diagnosis of sepsis. The current study is aiming to
      validate and improve performance of HemoSpec for the rapid assessment of the critically ill
      patient.
Sepsis is a life-threating organ dysfunction resulting from the dysregulated response of the
      host to an infection. It is estimated that 1.5 million people present with sepsis annually in
      Northern America and another 1.5 million people in Europe; 30 to 50% of them die making
      sepsis the leading cause of death. The key-point in the management of sepsis is the early
      resuscitation with broad-spectrum antimicrobials and intravenous fluids, if possible within
      the first hour. The great mortality of sepsis indicates that this goal is not easy to be
      achieved for two main reasons: the first is the delay in recognition of the septic patients
      and the second is the resistance of the implicated pathogen to broad-spectrum antimicrobials.

      In an attempt to improve the failure of physicians for early sepsis recognition, several
      markers have been developed. Some of them rely on clinical signs of the host and others on
      the measurements of circulating biomarkers. Recently, qSOFA (quick SOFA score) has been
      introduced to help the early recognition of sepsis in patients who present with infection
      outside the Intensive care Unit (ICU) i.e. either in the community or during hospitalization
      in the general ward1. However, there are concerns of the sensitivity of qSOFA and many
      introduce the need to measure biomarkers in serum. These biomarkers are usually protein
      molecules that are over-produced in the host as a result of the interaction with an infective
      insult. However, these protein molecules are produced by white blood cells. What is currently
      known is that although most of patients present with a similar phenotype, their
      pathophysiology is diverse. More precisely, although the majority of patients with sepsis
      present with high concentrations of protein molecules like interleukin (IL)-6, C-reactive
      protein (CRP) and procalcitonin (PCT) in their blood, in some patients circulating white
      blood cells remain over-active and in other patients they are significantly anergic, a
      situation often known as sepsis-induced immunoparalysis. Another molecule, called soluble
      urokinase plasminogen activator receptor (suPAR), is the shed uPAR receptor on neutrophils
      and is released in the circulation as a result of neutrophil activation; concentrations
      greater than 12 ng/ml can trace with negative predictive value almost 95% the patient at
      great chance of unfavorable outcome. As such, the robust diagnosis of sepsis may rely on a
      combination of clinical assessment, measurement of protein biomarkers and validation of the
      activity of circulating white blood cells.

      One FrameWork 7-funded initiative from seven European countries aims to develop a rapid score
      that can integrate all clinical and laboratory information and provide early diagnosis
      whether a patient has sepsis or not. The vision of this initiative is to build a device that
      is called HemoSpec. With this approach, whole blood coming from patients will be in parallel
      analyzed into three aspects: a) absolute white blood cell counting; b) information on the
      fluidity and activity of the white blood cells using Raman spectroscopy; and c) measurement
      of serum levels of IL-6, CRP, PCT and suPAR. The end result is building a diagnostic
      algorithm where clinical information is also taken into consideration.

      The project was started in November 2013 and the HemoSpec device is anticipated to be ready
      by February 2017. The diagnostic performance of HemoSpec is currently based on preliminary
      data coming from 60 patients (20 controls, 20 with systemic inflammatory response syndrome
      and 20 with sepsis) hospitalized in Jena University Hospital. The current study is aiming to
      validate and improve performance of HemoSpec for the rapid assessment of the critically ill
      patient in a larger phase II diagnostic study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Sensitivity of HemoSpec for the diagnosis of sepsis
time frame: 3 days
description: The sensitivity of HemoSpec output to diagnose the presence of sepsis compared to the absence of sepsis. HemoSpec output will be considered to provide a satisfactory diagnosis of sepsis if sensitivity for the diagnosis is greater than 85%.
measure: Diagnostic performance for sepsis
time frame: 3 days
description: The diagnostic performance of HemoSpec output to diagnose the presence of sepsis compared to the absence of sepsis. The diagnostic performance is composed by the aggregation of specificity, positive predictive value and negative predictive value.
measure: Prognostics performance for sepsis
time frame: 28 days
description: The prognostic performance of HemoSpec output to predict unfavorable outcome compared to survivors. The prognostic performance is composed by the aggregation of sensitivity, specificity, positive predictive value and negative predictive value.
measure: Prognostic performance for organ dysfunction
time frame: 28 days
description: The prognostic performance of HemoSpec output to predict progression into organ dysfunction. The prognostic performance is composed by the aggregation of sensitivity, specificity, positive predictive value and negative predictive value.
measure: Diagnostic performance over qSOFA
time frame: 3 days
description: The aggregation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HemoSpec output to indicate patients with infection among those scoring positive for qSOFA.
measure: Diagnostic performance and microbiology
time frame: 3 days
description: The diagnostic performance of HemoSpec output to diagnose the presence of sepsis between patients with microbiologically-proven infection and patients without microbiologically-proven infection. The diagnostic performance is composed by the aggregation of sensitivity, specificity, positive predictive value and negative predictive value.
arm group label: HemoSpec
arm group type: Experimental
description: Diagnosis of sepsis using HemoSpec device
intervention type: Device
intervention name: HemoSpec
description: Blood sampling for analysis
arm group label: HemoSpec
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Evangelos J Giamarellos-Bourboulis, MD, PhD
role: Study Chair
affiliation: National and Kapodistrian University of Athens
last name: Konstantinos Toutouzas, MD, PhD
role: Principal Investigator
affiliation: National and Kapodistrian University of Athens
last name: Athanasios Prekates, MD, PhD
role: Principal Investigator
affiliation: Tzaneion General Hospital
last name: Stylianos Karatzas, MD, PhD
role: Principal Investigator
affiliation: Ippokration General Hospital
last name: Christos Mathas, MD
role: Principal Investigator
affiliation: Aghia Olga General Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
country: Greece
citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
PMID: 26903338
citation: Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008 Mar;36(3):941-52. doi: 10.1097/CCM.0B013E318165BABB.
PMID: 18431284
citation: Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, Savva A, Tsangaris I, Dimopoulou I, Mouktaroudi M, Raftogiannis M, Georgitsi M, Linner A, Adamis G, Antonopoulou A, Apostolidou E, Chrisofos M, Katsenos C, Koutelidakis I, Kotzampassi K, Koratzanis G, Koupetori M, Kritselis I, Lymberopoulou K, Mandragos K, Marioli A, Sunden-Cullberg J, Mega A, Prekates A, Routsi C, Gogos C, Treutiger CJ, Armaganidis A, Dimopoulos G. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care. 2012 Aug 8;16(4):R149. doi: 10.1186/cc11463.
PMID: 22873681
responsible party type: Principal Investigator
investigator affiliation: University of Athens
investigator full name: Evangelos J. Giamarellos-Bourboulis, M.D.
investigator title: Associate Professor of Internal Medicine
mesh term: Sepsis
mesh term: Toxemia
sharing ipd: No