<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/NCT03781531</url>
  </required_header>
  <id_info>
    <org_study_id>dnr2017/260-31/4</org_study_id>
    <nct_id>NCT03781531</nct_id>
  </id_info>
  <brief_title>Identification of Novel Biomarkers to Aid in the Detection of Occult Cancer in Patients With Venous Thromboembolism</brief_title>
  <official_title>Identification of Novel Biomarkers to Aid in the Detection of Occult Cancer in Patients With Venous Thromboembolism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danderyd Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Danderyd Hospital</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>
      Venous thromboembolism is a common and serious complication in cancer, and is associated with&#xD;
      a substantially increased morbidity and mortality. Furthermore, VTE may be the earliest sign&#xD;
      of cancer. Recent studies, however, fail to show a clinical benefit of extended cancer&#xD;
      screening in this patient population. Better risk prediction models are therefore warranted&#xD;
      to identify VTE patients who would benefit from a rapid and extensive cancer screening.&#xD;
      Inflammation and hypercoagulability are considered hallmarks of cancer, and emerging light is&#xD;
      being shed on the potential of various markers of inflammation and coagulation in cancer&#xD;
      diagnostics and prognostics. Among the inflammatory and thrombotic processes linked to cancer&#xD;
      is the neutrophil release of web-like nuclear chromatin (DNA and histones), referred to as&#xD;
      neutrophil extracellular traps (NETs). Driven by the tumor environment, NETs have recently&#xD;
      been shown to play a central role in tumor progression, metastasis, and tumor-associated&#xD;
      thrombosis.&#xD;
&#xD;
      The investigators hypothesize that an enhanced inflammatory state may be predictive of an&#xD;
      underlying cancer in patients presenting with VTE. The present study is an ongoing&#xD;
      prospective study with the primary aim to investigate the diagnostic potential of markers of&#xD;
      inflammation, including markers of NETs, in detecting occult cancer in patients presenting&#xD;
      with VTE. Secondary aims are to include other biomarkers of cancer, and to assess whether any&#xD;
      or a combination of these biomarkers may be prognostic of occult cancer, recurrent thrombotic&#xD;
      events, mortality, or cancer disease progression in VTE patients with an underlying&#xD;
      malignancy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>Cancer</measure>
    <time_frame>Within 2 years from study inclusion</time_frame>
    <description>Patients diagnosed with VTE will be referred for a limited cancer screening according to current guidelines. Cancer diagnosis - if not present at inclusion - will be obtained during a two-year follow-up from hospital records and/or the Swedish cancer registry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrent thrombotic event</measure>
    <time_frame>Within 2 years from study inclusion</time_frame>
    <description>Recurrent thrombotic event (arterial or venous thrombosis) will be obtained during a two-year follow-up from hospital records and/or the Swedish national patient registry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>Within 2 years from study inclusion</time_frame>
    <description>All-cause mortality will be obtained during a two-year follow-up from hospital records and/or the Swedish death registry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cancer progression among enrolled patients with a cancer diagnosis at study inclusion</measure>
    <time_frame>Within 2 years from study inclusion</time_frame>
    <description>Patients with cancer progression will be identified during a two-year follow-up from hospital records and/or the Swedish cancer registry</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Cancer</condition>
  <condition>Venous Thromboembolism</condition>
  <arm_group>
    <arm_group_label>Venous thromboembolism</arm_group_label>
    <description>Patients presenting with venous thromboembolism (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or pulmonary embolism) as detected by ultrasonography, phlebography, computer tomography, or angiography</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Consecutive patients age &gt;18 years with objectively confirmed venous thromboembolism&#xD;
        (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or&#xD;
        pulmonary embolism) diagnosed &lt; 2 days.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Venous thromboembolism (thrombosis in the deep venous system of upper or lower&#xD;
             extremities or iliac veins and/or pulmonary embolism) as detected by ultrasonography,&#xD;
             phlebography, computer tomography, or angiography;&#xD;
&#xD;
          -  &gt; 18 years or older;&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &gt; 2 days after VTE diagnosis;&#xD;
&#xD;
          -  No blood withdrawal at baseline&#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>Charlotte Thålin, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Håkan Wallén, M.D., Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Charlotte Thålin, M.D., Ph.D.</last_name>
    <phone>+46709565120</phone>
    <email>charlotte.thalin@sll.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Håkan Wallén, M.D., Prof.</last_name>
    <phone>+46707374935</phone>
    <email>hakan.wallen@ki.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Danderyd Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>18350</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Charlotte Thålin, M.D., Ph.D.</last_name>
      <phone>+46709565120</phone>
      <email>charlotte.thalin@sll.se</email>
    </contact>
    <contact_backup>
      <last_name>Lena Gabrielsson</last_name>
      <phone>+46737121286</phone>
      <email>lena.gabrielsson@sll.se</email>
    </contact_backup>
    <investigator>
      <last_name>Charlotte Thålin, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Håkan Wallén, M.D., Prof.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Södersjukhuset</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mårten Söderberg, M.D., Ph.D.</last_name>
      <phone>+4686160000</phone>
      <email>marten.soderberg@sll.se</email>
    </contact>
    <investigator>
      <last_name>Charlotte Thålin, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Håkan Wallén, M.D., Prof.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>December 18, 2018</last_update_submitted>
  <last_update_submitted_qc>December 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Occult cancer</keyword>
  <keyword>Venous thromboembolism</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Early diagnosis</keyword>
  <keyword>Neutrophil extracellular traps</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</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/NCT03781531
org study id: dnr2017/260-31/4
nct id: NCT03781531
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Venous thromboembolism is a common and serious complication in cancer, and is associated with
      a substantially increased morbidity and mortality. Furthermore, VTE may be the earliest sign
      of cancer. Recent studies, however, fail to show a clinical benefit of extended cancer
      screening in this patient population. Better risk prediction models are therefore warranted
      to identify VTE patients who would benefit from a rapid and extensive cancer screening.
      Inflammation and hypercoagulability are considered hallmarks of cancer, and emerging light is
      being shed on the potential of various markers of inflammation and coagulation in cancer
      diagnostics and prognostics. Among the inflammatory and thrombotic processes linked to cancer
      is the neutrophil release of web-like nuclear chromatin (DNA and histones), referred to as
      neutrophil extracellular traps (NETs). Driven by the tumor environment, NETs have recently
      been shown to play a central role in tumor progression, metastasis, and tumor-associated
      thrombosis.

      The investigators hypothesize that an enhanced inflammatory state may be predictive of an
      underlying cancer in patients presenting with VTE. The present study is an ongoing
      prospective study with the primary aim to investigate the diagnostic potential of markers of
      inflammation, including markers of NETs, in detecting occult cancer in patients presenting
      with VTE. Secondary aims are to include other biomarkers of cancer, and to assess whether any
      or a combination of these biomarkers may be prognostic of occult cancer, recurrent thrombotic
      events, mortality, or cancer disease progression in VTE patients with an underlying
      malignancy.
observational model: Cohort
time perspective: Prospective
measure: Cancer
time frame: Within 2 years from study inclusion
description: Patients diagnosed with VTE will be referred for a limited cancer screening according to current guidelines. Cancer diagnosis - if not present at inclusion - will be obtained during a two-year follow-up from hospital records and/or the Swedish cancer registry
measure: Recurrent thrombotic event
time frame: Within 2 years from study inclusion
description: Recurrent thrombotic event (arterial or venous thrombosis) will be obtained during a two-year follow-up from hospital records and/or the Swedish national patient registry
measure: All-cause mortality
time frame: Within 2 years from study inclusion
description: All-cause mortality will be obtained during a two-year follow-up from hospital records and/or the Swedish death registry
measure: Cancer progression among enrolled patients with a cancer diagnosis at study inclusion
time frame: Within 2 years from study inclusion
description: Patients with cancer progression will be identified during a two-year follow-up from hospital records and/or the Swedish cancer registry
arm group label: Venous thromboembolism
description: Patients presenting with venous thromboembolism (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or pulmonary embolism) as detected by ultrasonography, phlebography, computer tomography, or angiography
Blood samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charlotte Thålin, M.D., Ph.D.
role: Principal Investigator
affiliation: Karolinska Institutet
last name: Håkan Wallén, M.D., Prof.
role: Principal Investigator
affiliation: Karolinska Institutet
last name: Charlotte Thålin, M.D., Ph.D.
phone: +46709565120
email: charlotte.thalin@sll.se
last name: Håkan Wallén, M.D., Prof.
phone: +46707374935
email: hakan.wallen@ki.se
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Sweden
responsible party type: Sponsor
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
sharing ipd: Undecided