<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/NCT03812666</url>
  </required_header>
  <id_info>
    <org_study_id>247991</org_study_id>
    <secondary_id>2018/288</secondary_id>
    <nct_id>NCT03812666</nct_id>
  </id_info>
  <brief_title>Search for Biomarkers of Infection and Inflammation in Patients With Acute Stroke.</brief_title>
  <acronym>IBIS</acronym>
  <official_title>Inflammatory Biomarkers In Stroke - Discovery Phase</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jakob Ström</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Örebro University, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Region Örebro County</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>
      This study will look for new biomarkers of infection and evaluate current biomarkers of&#xD;
      infection in stroke patients. Patients with acute stroke will be monitored with daily blood&#xD;
      samples for seven days and by clinical examination to detect infections for 10 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Stroke is one of the leading causes of death globally, and infections after stroke&#xD;
      contribute to a large part of the stroke-related mortality. The current study, which has a&#xD;
      prospective, observational design, constitutes the second phase out of four in the&#xD;
      Inflammatory Biomarkers In Stroke (IBIS) project, of which the overall goal is to enable&#xD;
      early treatment of post-stroke infections.&#xD;
&#xD;
      Aim: To develop a combined clinical and molecular biological signature for early detection of&#xD;
      pneumonia in patients with stroke.&#xD;
&#xD;
      Design: Prospective nested case control study&#xD;
&#xD;
      Methods:Patients (n=200) with acute stroke will be monitored with clinical examinations for&#xD;
      ten days and by daily blood samples for seven days. When cases of pneumonia have been&#xD;
      established, samples and examination results from days preceding overt pneumonia will be&#xD;
      compared to samples from similar patients that did not develop pneumonia.&#xD;
&#xD;
      Outcome: Using proteomic and metabolomic methods, novel markers of upcoming pneumonia after&#xD;
      stroke will be sought. Such laboratory markers will be combined with current biomarkers (such&#xD;
      as C-reactive protein and procalcitonin) and data from clinical examinations, with the aim of&#xD;
      constructing a biological signature that enables early detection of pneumonia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Novel biomarkers of pneumonia</measure>
    <time_frame>The day before pneumonia onset.</time_frame>
    <description>The study will analyze a broad expanse of potential biomarkers, including known markers of infection such as c-reactive protein, procalcitonin and increased respiratory frequency as well as novel markers that will be pursued using proteomic and metabolomic methods. Those that are significantly associated with upcoming pneumonia will be selected. Biomarkers will be evaluated by the area under the curve for the receiver operating characteristic (AUC-ROC).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>A combined clinical and molecular biological signature for early detection of pneumonia</measure>
    <time_frame>The day before pneumonia onset.</time_frame>
    <description>By combining novel (found using proteomic and metabolomic methods) and current biomarkers (such as c-reactive protein, procalcitonin and increased respiratory frequency) with data from clinical examinations, a biological signature that enables early detection of pneumonia will be constructed.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Stroke, Acute</condition>
  <condition>Pneumonia, Bacterial</condition>
  <arm_group>
    <arm_group_label>Severe stroke</arm_group_label>
    <description>Patients with severe (defined as NIHSS score of &gt; 10) acute stroke, either ischemic or hemorrhagic. (n= 150)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderately stroke</arm_group_label>
    <description>Patients with moderately severe (defined as NIHSS score of &gt; 5 but &lt; 11) acute stroke, either ischemic or hemorrhagic. (n= 25)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mild stroke</arm_group_label>
    <description>Patients with mild (defined as NIHSS score of &lt;6) acute stroke, either ischemic or hemorrhagic. (n= 25)</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Daily blood samples for 7 days as well as a 90-day follow-up blood sample will be stored in a&#xD;
      biobank for later analysis&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Eligible patients admitted to Örebro University hospital will be consecutively offered&#xD;
        enrollement. The sample is weighted to include more patients with severe stroke (defined as&#xD;
        NIHSS ≥ 11) than with moderate (NIHSS ≤10 and ≥ 6) or mild (NIHSS ≤5) stroke. The purpose&#xD;
        of this is to ensure that a high proportion of participants will contract pneumonia since&#xD;
        patients with a more severe stroke have a higher risk of pneumonia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Symptoms and radiology consistent with acute cerebral infarction or atraumatic&#xD;
             intracerebral hemorrhage.&#xD;
&#xD;
          -  National Institutes of Health Stroke Scale (NIHSS) ≤5; mild stroke (n=25), NIHSS ≤10&#xD;
             and ≥ 6; moderate stroke (n=25) or NIHSS ≥ 11; severe stroke (n=150)&#xD;
&#xD;
          -  Onset of symptoms less than 48 hours before first study blood sampling.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptoms and radiology consistent with acute cerebral infarction but full reversal of&#xD;
             symptoms within 24 hours of onset. (i.e. transient ischemic attack, TIA)&#xD;
&#xD;
          -  Hemoglobin less than 90 g/l.&#xD;
&#xD;
          -  Ongoing inflammatory disease, such as rheumatoid arthritis or active inflammatory&#xD;
             bowel disease.&#xD;
&#xD;
          -  Inability to undergo MRI scan (only patients with NIHSS ≤10 will be excluded by this&#xD;
             criteria)&#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>Jakob Ström, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Region Örebro County</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Örebro University Hospital</name>
      <address>
        <city>Örebro</city>
        <state>Örebro Län</state>
        <zip>701 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>November 2, 2022</last_update_submitted>
  <last_update_submitted_qc>November 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Region Örebro County</investigator_affiliation>
    <investigator_full_name>Jakob Ström</investigator_full_name>
    <investigator_title>Jakob Ström, MD, PhD, resident of neurology and Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Stroke</keyword>
  <keyword>Pneumonia</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Bacterial</mesh_term>
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03812666
org study id: 247991
secondary id: 2018/288
nct id: NCT03812666
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will look for new biomarkers of infection and evaluate current biomarkers of
      infection in stroke patients. Patients with acute stroke will be monitored with daily blood
      samples for seven days and by clinical examination to detect infections for 10 days.
Rationale: Stroke is one of the leading causes of death globally, and infections after stroke
      contribute to a large part of the stroke-related mortality. The current study, which has a
      prospective, observational design, constitutes the second phase out of four in the
      Inflammatory Biomarkers In Stroke (IBIS) project, of which the overall goal is to enable
      early treatment of post-stroke infections.

      Aim: To develop a combined clinical and molecular biological signature for early detection of
      pneumonia in patients with stroke.

      Design: Prospective nested case control study

      Methods:Patients (n=200) with acute stroke will be monitored with clinical examinations for
      ten days and by daily blood samples for seven days. When cases of pneumonia have been
      established, samples and examination results from days preceding overt pneumonia will be
      compared to samples from similar patients that did not develop pneumonia.

      Outcome: Using proteomic and metabolomic methods, novel markers of upcoming pneumonia after
      stroke will be sought. Such laboratory markers will be combined with current biomarkers (such
      as C-reactive protein and procalcitonin) and data from clinical examinations, with the aim of
      constructing a biological signature that enables early detection of pneumonia.
observational model: Case-Control
time perspective: Prospective
measure: Novel biomarkers of pneumonia
time frame: The day before pneumonia onset.
description: The study will analyze a broad expanse of potential biomarkers, including known markers of infection such as c-reactive protein, procalcitonin and increased respiratory frequency as well as novel markers that will be pursued using proteomic and metabolomic methods. Those that are significantly associated with upcoming pneumonia will be selected. Biomarkers will be evaluated by the area under the curve for the receiver operating characteristic (AUC-ROC).
measure: A combined clinical and molecular biological signature for early detection of pneumonia
time frame: The day before pneumonia onset.
description: By combining novel (found using proteomic and metabolomic methods) and current biomarkers (such as c-reactive protein, procalcitonin and increased respiratory frequency) with data from clinical examinations, a biological signature that enables early detection of pneumonia will be constructed.
arm group label: Severe stroke
description: Patients with severe (defined as NIHSS score of > 10) acute stroke, either ischemic or hemorrhagic. (n= 150)
arm group label: Moderately stroke
description: Patients with moderately severe (defined as NIHSS score of > 5 but < 11) acute stroke, either ischemic or hemorrhagic. (n= 25)
arm group label: Mild stroke
description: Patients with mild (defined as NIHSS score of <6) acute stroke, either ischemic or hemorrhagic. (n= 25)
Daily blood samples for 7 days as well as a 90-day follow-up blood sample will be stored in a
      biobank for later analysis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jakob Ström, MD, PhD
role: Principal Investigator
affiliation: Region Örebro County
facility: 
country: Sweden
responsible party type: Sponsor-Investigator
investigator affiliation: Region Örebro County
investigator full name: Jakob Ström
investigator title: Jakob Ström, MD, PhD, resident of neurology and Associate Professor
mesh term: Pneumonia
mesh term: Pneumonia, Bacterial
mesh term: Stroke
sharing ipd: Undecided