<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/NCT02262052</url>
  </required_header>
  <id_info>
    <org_study_id>LeidenU</org_study_id>
    <nct_id>NCT02262052</nct_id>
  </id_info>
  <brief_title>Advanced Diagnostic Management of Suspected Recurrent Ipsilateral DVT With MRDTI</brief_title>
  <acronym>Theia</acronym>
  <official_title>Advanced Diagnostic Management of Suspected Recurrent Ipsilateral Deep Vein Thrombosis of the Leg With Magnetic Resonance Direct Thrombus Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Trombosestichting Nederland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Leiden University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Theia-study is a prospective, multicenter, single-arm management (cohort) study.&#xD;
&#xD;
      Consecutive patients with clinically suspected acute, recurrent, ipsilateral, proximal deep&#xD;
      vein thrombosis (DVT) of the leg, who fulfil all the inclusion criteria and meet none of the&#xD;
      exclusion criteria, are eligible for inclusion and will be managed according to the result of&#xD;
      a magnetic resonance direct thrombus imaging (MRDTI) of the affected leg. The MRDTI is to be&#xD;
      performed and adjudicated within 24 hours of study inclusion. The final treatment decision&#xD;
      will be made based on this ruling of the MRDTI. In case of a positive MRDTI signal, patients&#xD;
      will be treated with therapeutically dosed anticoagulants or modified in patients with a&#xD;
      recurrent DVT on anticoagulant therapy. Patients with a negative MRDTI ruling will be left&#xD;
      untreated, or treatment will be remained unadjusted if they are on anticoagulant treatment at&#xD;
      inclusion. All patients with negative MRDTI will be subjected to a standardized compression&#xD;
      ultrasonography (CUS) within 48 hours after initial presentation. The latter CUS serves as a&#xD;
      reference test in case the patient returns with symptoms of ipsilateral recurrence in the&#xD;
      future, and will not be used for management decisions at baseline. The study flowchart can be&#xD;
      found in Appendix A.&#xD;
&#xD;
      All patients will be followed for three months for the occurrence of acute recurrent venous&#xD;
      thrombo-embolism (VTE). In case of suspected recurrent VTE, objective testing including&#xD;
      either computed tomography pulmonary angiography (CTPA) for PE or CUS for DVT will be&#xD;
      performed. Additionally, in case of a proven ipsilateral recurrent DVT during follow-up,&#xD;
      MRDTI will be repeated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      See below.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 26, 2015</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">March 2019</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>3-month incidence of recurrent VTE in patients with negative MRDTI</measure>
    <time_frame>3-month follow-up</time_frame>
    <description>Primary outcome is subdivided in two main outcomes: 3-month incidence of recurrent VTE in 1) patients with negative MRDTI for both DVT and thrombophlebitis who were not treated with any anticoagulant during follow-up and 2) all patients with negative MRDTI for DVT; these recurrences need to be objectively confirmed by either CT (for acute PE), or CUS with the baseline CUS serving as reference.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>3-month incidence of recurrent VTE in patients with normal D-dimer test and unlikely clinical probability according to the Wells clinical decision rule for DVT</measure>
    <time_frame>3-month follow-up</time_frame>
    <description>the 3-month incidence of recurrent VTE in patients with low probability Wells score and a normal D-dimer test at baseline</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The feasibility of MRDTI in day to day clinical practice</measure>
    <time_frame>First 24 hours after presentation to the emergency ward (post-hoc analysis)</time_frame>
    <description>The feasibility of MRDTI in day to day clinical practice: percentage of eligible patients that had to be excluded due to logistic reasons such as unavailability of MRDTI within 24 hours of presentation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Inter-observer variability of MRDTI</measure>
    <time_frame>After the study has been completed, all MRDTI studies will be re-evaluated (post-hoc analysis)</time_frame>
    <description>The inter-observer variability of MRDTI in daily clinical practice: all MRDTI scans will be review post-hoc by two independent experts to determine the alpha statistic between the readings in clinical practice and that by experts.</description>
  </other_outcome>
  <other_outcome>
    <measure>a formal cost-effectiveness and cost-utility analysis</measure>
    <time_frame>This model will be based on the primary and secondary endpoints, scored after a follow-up period of 3 months (post-hoc analysis)</time_frame>
    <description>A Markov model will be developed to estimate the cost-effectiveness MRDTI versus ultrasonography. The model will follow the patients through the course of disease in a maximum of two three-month cycles, and will include all relevant clinical outcomes and incorporated health states stratified by diagnostic management. Clinical events included in the model are fatal PE, recurrent VTE, major bleeds and clinically relevant non-major. The model includes clinical and cost outcomes, along with incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMBs).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">305</enrollment>
  <condition>Deep Vein Thrombosis</condition>
  <arm_group>
    <arm_group_label>Phase 4 cohort study</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>MRDTI</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRDTI</intervention_name>
    <description>MRDTI is primary diagnostic test for management of suspected ipsilateral DVT</description>
    <arm_group_label>Phase 4 cohort study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability of subject to understand the character and individual consequences of this&#xD;
             study;&#xD;
&#xD;
          2. Signed and dated informed consent of the subject available before the start of any&#xD;
             specific study procedures;&#xD;
&#xD;
          3. Age ≥18 years;&#xD;
&#xD;
          4. Suspected acute recurrent ipsilateral DVT, as defined by a documented prior&#xD;
             objectivated episode of DVT in the same leg as current symptoms originate from&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. General contraindications for MRI: claustrophobia, pregnancy, intracranial vascular&#xD;
             clips, any ferromagnetic implants, presence of a cardiac pacemaker or defibrillator,&#xD;
             metallic splinters in the eye, any trauma or surgery which may have left ferromagnetic&#xD;
             material in the body;&#xD;
&#xD;
          2. CUS-proven acute symptomatic DVT within 6 months before current presentation;&#xD;
&#xD;
          3. Onset of symptoms suggestive of acute recurrent DVT more than 10 days prior to&#xD;
             presentation;&#xD;
&#xD;
          4. Suspected acute PE;&#xD;
&#xD;
          5. Hemodynamic instability at presentation (as a consequence of concurrent acute PE or&#xD;
             otherwise);&#xD;
&#xD;
          6. Medical or psychological condition that would not permit completion of the study or&#xD;
             signing of informed consent, including life expectancy less than 3 months, or&#xD;
             unwillingness to sign informed consent;&#xD;
&#xD;
          7. Non-compliance or inability to adhere to treatment or follow-up visits.&#xD;
&#xD;
          8. Patients with suspected acute, recurrent, ipsilateral DVT on therapeutic anticoagulant&#xD;
             treatment &gt; 48 hours at inclusion*&#xD;
&#xD;
        Note: *From August 2015 onward, patients with suspected acute, recurrent, ipsilateral DVT&#xD;
        on anticoagulant treatment were allowed in the study as they were found to represent a high&#xD;
        proportion (30%) of the screened study population.&#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>F.A. Klok Klok, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Thrombosis and Hemostasis, LUMC, Leiden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>M.V. Huisman, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Thrombosis and Hemostasis, LUMC, Leiden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>L.J.M. Kroft, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Radiology, LUMC, Leiden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RAMBAM Healthcare center</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AMC</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rijnstate</name>
      <address>
        <city>Arnhem</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deventer Ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LUMC</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HAGA</name>
      <address>
        <city>The Hague</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MCH Westeinde</name>
      <address>
        <city>The Hague</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diakonessenhuis Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3582 KE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCU</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ostfold Hospital Trust</name>
      <address>
        <city>Grålum</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Danderyds sjukhus</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Israel</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <results_reference>
    <citation>Tan M, Mol GC, van Rooden CJ, Klok FA, Westerbeek RE, Iglesias Del Sol A, van de Ree MA, de Roos A, Huisman MV. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis. Blood. 2014 Jul 24;124(4):623-7. doi: 10.1182/blood-2014-04-566380. Epub 2014 Jun 13.</citation>
    <PMID>24928859</PMID>
  </results_reference>
  <results_reference>
    <citation>Westerbeek RE, Van Rooden CJ, Tan M, Van Gils AP, Kok S, De Bats MJ, De Roos A, Huisman MV. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg. J Thromb Haemost. 2008 Jul;6(7):1087-92. doi: 10.1111/j.1538-7836.2008.02986.x. Epub 2008 Jul 1.</citation>
    <PMID>18433464</PMID>
  </results_reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>September 4, 2019</last_update_submitted>
  <last_update_submitted_qc>September 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
    <investigator_full_name>Erik Klok</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>Deep vein thrombosis</keyword>
  <keyword>Diagnostic management</keyword>
  <keyword>Recurrent</keyword>
  <keyword>MRI</keyword>
  <keyword>Ipsilateral</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Venous Thrombosis</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/NCT02262052
org study id: LeidenU
nct id: NCT02262052
lead sponsor: 
collaborator: 
has dmc: No
The Theia-study is a prospective, multicenter, single-arm management (cohort) study.

      Consecutive patients with clinically suspected acute, recurrent, ipsilateral, proximal deep
      vein thrombosis (DVT) of the leg, who fulfil all the inclusion criteria and meet none of the
      exclusion criteria, are eligible for inclusion and will be managed according to the result of
      a magnetic resonance direct thrombus imaging (MRDTI) of the affected leg. The MRDTI is to be
      performed and adjudicated within 24 hours of study inclusion. The final treatment decision
      will be made based on this ruling of the MRDTI. In case of a positive MRDTI signal, patients
      will be treated with therapeutically dosed anticoagulants or modified in patients with a
      recurrent DVT on anticoagulant therapy. Patients with a negative MRDTI ruling will be left
      untreated, or treatment will be remained unadjusted if they are on anticoagulant treatment at
      inclusion. All patients with negative MRDTI will be subjected to a standardized compression
      ultrasonography (CUS) within 48 hours after initial presentation. The latter CUS serves as a
      reference test in case the patient returns with symptoms of ipsilateral recurrence in the
      future, and will not be used for management decisions at baseline. The study flowchart can be
      found in Appendix A.

      All patients will be followed for three months for the occurrence of acute recurrent venous
      thrombo-embolism (VTE). In case of suspected recurrent VTE, objective testing including
      either computed tomography pulmonary angiography (CTPA) for PE or CUS for DVT will be
      performed. Additionally, in case of a proven ipsilateral recurrent DVT during follow-up,
      MRDTI will be repeated.
See below.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: 3-month incidence of recurrent VTE in patients with negative MRDTI
time frame: 3-month follow-up
description: Primary outcome is subdivided in two main outcomes: 3-month incidence of recurrent VTE in 1) patients with negative MRDTI for both DVT and thrombophlebitis who were not treated with any anticoagulant during follow-up and 2) all patients with negative MRDTI for DVT; these recurrences need to be objectively confirmed by either CT (for acute PE), or CUS with the baseline CUS serving as reference.
measure: 3-month incidence of recurrent VTE in patients with normal D-dimer test and unlikely clinical probability according to the Wells clinical decision rule for DVT
time frame: 3-month follow-up
description: the 3-month incidence of recurrent VTE in patients with low probability Wells score and a normal D-dimer test at baseline
measure: The feasibility of MRDTI in day to day clinical practice
time frame: First 24 hours after presentation to the emergency ward (post-hoc analysis)
description: The feasibility of MRDTI in day to day clinical practice: percentage of eligible patients that had to be excluded due to logistic reasons such as unavailability of MRDTI within 24 hours of presentation.
measure: Inter-observer variability of MRDTI
time frame: After the study has been completed, all MRDTI studies will be re-evaluated (post-hoc analysis)
description: The inter-observer variability of MRDTI in daily clinical practice: all MRDTI scans will be review post-hoc by two independent experts to determine the alpha statistic between the readings in clinical practice and that by experts.
measure: a formal cost-effectiveness and cost-utility analysis
time frame: This model will be based on the primary and secondary endpoints, scored after a follow-up period of 3 months (post-hoc analysis)
description: A Markov model will be developed to estimate the cost-effectiveness MRDTI versus ultrasonography. The model will follow the patients through the course of disease in a maximum of two three-month cycles, and will include all relevant clinical outcomes and incorporated health states stratified by diagnostic management. Clinical events included in the model are fatal PE, recurrent VTE, major bleeds and clinically relevant non-major. The model includes clinical and cost outcomes, along with incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMBs).
arm group label: Phase 4 cohort study
arm group type: Other
description: MRDTI
intervention type: Other
intervention name: MRDTI
description: MRDTI is primary diagnostic test for management of suspected ipsilateral DVT
arm group label: Phase 4 cohort study
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: F.A. Klok Klok, MD PhD
role: Principal Investigator
affiliation: Department of Thrombosis and Hemostasis, LUMC, Leiden
last name: M.V. Huisman, Prof
role: Principal Investigator
affiliation: Department of Thrombosis and Hemostasis, LUMC, Leiden
last name: L.J.M. Kroft, MD PhD
role: Principal Investigator
affiliation: Department of Radiology, LUMC, Leiden
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Israel
country: Netherlands
country: Norway
country: Sweden
citation: Tan M, Mol GC, van Rooden CJ, Klok FA, Westerbeek RE, Iglesias Del Sol A, van de Ree MA, de Roos A, Huisman MV. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis. Blood. 2014 Jul 24;124(4):623-7. doi: 10.1182/blood-2014-04-566380. Epub 2014 Jun 13.
PMID: 24928859
citation: Westerbeek RE, Van Rooden CJ, Tan M, Van Gils AP, Kok S, De Bats MJ, De Roos A, Huisman MV. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg. J Thromb Haemost. 2008 Jul;6(7):1087-92. doi: 10.1111/j.1538-7836.2008.02986.x. Epub 2008 Jul 1.
PMID: 18433464
responsible party type: Principal Investigator
investigator affiliation: Leiden University Medical Center
investigator full name: Erik Klok
investigator title: Dr
mesh term: Thrombosis
mesh term: Venous Thrombosis