<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/NCT01662908</url>
  </required_header>
  <id_info>
    <org_study_id>DU176b-D-U211</org_study_id>
    <nct_id>NCT01662908</nct_id>
  </id_info>
  <brief_title>A Randomized, Open-Label, Parallel-Group, Multi-Center Study for the Evaluation of Efficacy and Safety of Edoxaban Monotherapy Versus Low Molecular Weight (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis</brief_title>
  <acronym>eTRIS</acronym>
  <official_title>A Randomized, Open-Label, Parallel-Group, Multi-Center Study for the Evaluation of Efficacy and Safety of Edoxaban Monotherapy Versus (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis - Edoxaban Thrombus Reduction Imaging Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daiichi Sankyo, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assess the relative change in thrombus volume as determined by two assessments (Baseline and&#xD;
      Day 14-21) with magnetic resonance venography (MRV) in subjects with deep-vein thrombosis&#xD;
      (DVT) treated with either an edoxaban monotherapy regimen or a low molecular weight (LMW)&#xD;
      heparin/warfarin regimen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The classical management of patients with venous thromboembolism (VTE) consists of an initial&#xD;
      treatment of at least five days of a (LMW) heparin followed by long-term treatment with a&#xD;
      vitamin K antagonist (VKA), such as warfarin. The eTRIS study will address the clinically&#xD;
      important question of whether edoxaban monotherapy, without concomitant (LMW) heparin at the&#xD;
      time of treatment initiation is comparable to or better than standard treatment with (LMW)&#xD;
      heparin/warfarin therapy in subjects with acute symptomatic DVT as assessed by the relative&#xD;
      change from baseline in thrombus volume (measured by MRI) at Day 14-21.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relative Change From Baseline in Thrombus Volume Assessed by MRI [Using the Magnetic Resonance Venography (MRV) Method]</measure>
    <time_frame>Baseline to final visit (Day 14-21)</time_frame>
    <description>Thrombus Volume (mm^3) was measured at baseline and between days 14 to 21 using MRI results as determined by Magnetic Resonance Venography (MRV) method, and the relative percentage change from baseline was calculated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Relevant Bleeding</measure>
    <time_frame>Initial dose of study drug up to 3 days after last dose</time_frame>
    <description>Clinically relevant bleeding was defined as major or clinically relevant non-major bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Recurrence of Venous Thromboembolism (VTE)</measure>
    <time_frame>Baseline to final visit (Day 14-21)</time_frame>
    <description>Number of participants with investigator-confirmed recurrent VTE events that start or worsen after the first dose of study drug and prior to the date of the final visit or telephone contact (inclusive)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Major Adverse Cardiovascular Events (MACE)</measure>
    <time_frame>Initial dose of study drug up to 3 days after last dose</time_frame>
    <description>MACE is defined as a composite of non-fatal myocardial infarction (MI), non-fatal stroke, non-fatal systemic embolic event (SEE) and cardiovascular death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Change From Baseline in the Presence or Absence of Thrombus by Vessel</measure>
    <time_frame>Baseline to final visit (Day 14-21)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">85</enrollment>
  <condition>Deep Vein Thrombosis</condition>
  <condition>Venous Thrombosis</condition>
  <arm_group>
    <arm_group_label>edoxaban tosylate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>heparin/warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>edoxaban tosylate</intervention_name>
    <description>edoxaban tosylate (DU-176b), film-coated for oral use, 90 mg once daily (QD) for 10 days (±2 days) followed by 60 mg QD for a total of approximately 90 days of edoxaban treatment</description>
    <arm_group_label>edoxaban tosylate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>enoxaparin/unfractionated heparin</intervention_name>
    <description>enoxaparin - administered by subcutaneous injection;1 mg/kg/ twice daily or 1.5 mg/kg once daily unfractionated heparin - started with 5000 IU bolus intravenous administration, 1300 IU/h continuous infusion, minimum of 5 days of treatment and stopped when target INR (2.0 - 3.0) is achieved.</description>
    <arm_group_label>heparin/warfarin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>warfarin</intervention_name>
    <description>tablet for oral use; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; 90 days treatment.</description>
    <arm_group_label>heparin/warfarin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects older than the minimum legal adult age (country specific)&#xD;
&#xD;
          -  Acute symptomatic proximal DVT involving the popliteal, femoral or iliac veins&#xD;
             confirmed by compression ultrasonography (CUS) or other appropriate imaging techniques&#xD;
             (such as venography or spiral/contrast CT) with symptom onset &lt; or = 1week prior to&#xD;
             randomization&#xD;
&#xD;
          -  Able to provide signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant pulmonary embolism known to the investigator at the time of randomization&#xD;
&#xD;
          -  Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the&#xD;
             current episode of DVT&#xD;
&#xD;
          -  Indication for warfarin other than DVT&#xD;
&#xD;
          -  More than 48 hours pre-treatment with therapeutic dosages of anti-coagulant treatment&#xD;
             [low molecular weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, VKA,&#xD;
             factor Xa inhibitor or other anti coagulant per local labeling] prior to randomization&#xD;
             to treat the current episode&#xD;
&#xD;
          -  Treatment with any investigational drug within 30 days prior to randomization&#xD;
&#xD;
          -  Calculated creatinine clearance (CrCL) &lt; 30 mL/min&#xD;
&#xD;
          -  Significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis)&#xD;
             or alanine aminotransferase (ALT) &gt; or = 2 times the upper limit of normal (ULN), or&#xD;
             total bilirubin (TBL) &gt; or = to 1.5 times the ULN (however subjects whose elevated TBL&#xD;
             is due to known Gilbert's syndrome may be included in the study)&#xD;
&#xD;
          -  Subjects with active cancer for whom long term treatment with (LMW) heparin is&#xD;
             anticipated&#xD;
&#xD;
          -  Life expectancy &lt; 3 months&#xD;
&#xD;
          -  Active bleeding or high risk for bleeding contraindicating treatment with (LMW)&#xD;
             heparin or warfarin&#xD;
&#xD;
          -  Uncontrolled hypertension as judged by the Investigator (e.g., systolic blood pressure&#xD;
             &gt; 170 mmHg or diastolic blood pressure &gt; 100 mmHg despite antihypertensive medications&#xD;
             confirmed by repeat measurement)&#xD;
&#xD;
          -  Women of childbearing potential without proper contraceptive measures (i.e., a method&#xD;
             of contraception with a failure rate &lt; 1 % during the course of the study including&#xD;
             the observational period) and women who are pregnant or breast feeding&#xD;
&#xD;
          -  Any contraindication listed in the local labeling of LMWH, UFH, or warfarin&#xD;
&#xD;
          -  Chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs)&#xD;
             including both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX- 2) inhibitors for &gt;&#xD;
             or = 4 days/week anticipated to continue during the study.&#xD;
&#xD;
          -  Treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet&#xD;
             therapy (any two antiplatelet agents including aspirin plus any other oral or&#xD;
             intravenous [IV] antiplatelet drug) anticipated to continue during the study&#xD;
&#xD;
          -  Treatment with P-gp inhibitors is not permitted at the time of randomization;&#xD;
             subsequent use is permitted, with a dose reduction in the edoxaban monotherapy&#xD;
             treatment arm.&#xD;
&#xD;
          -  Known history of positive Hepatitis B antigen or Hepatitis C antibody&#xD;
&#xD;
          -  Subjects with any condition that, as judged by the investigator, would put the subject&#xD;
             at increased risk of harm if he/she participated in the study; including, but not&#xD;
             limited to, subjects at increased risk of harm if given a gadolinium-based contrast&#xD;
             agent such as gadofosveset trisodium (Ablavar®)&#xD;
&#xD;
          -  Subjects for whom MRI would be contraindicated (e.g., subjects with metal implants) or&#xD;
             for whom the use of a gadolinium-based contrast agent such as gadofosveset trisodium&#xD;
             (Ablavar®) would be contraindicated&#xD;
&#xD;
          -  Subject has previously entered this study or another edoxaban study&#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>Samuel Z Goldhaber, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Dothan</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlantis</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jonesboro</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paducah</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Covington</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Annapolis</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Randallstown</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Butte</city>
        <state>Montana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wilmington</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Maumee</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Camp Hill</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ephrata</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sellersville</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fredericksburg</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Market</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greenfield Park</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>September 28, 2016</results_first_submitted>
  <results_first_submitted_qc>April 5, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 12, 2017</results_first_posted>
  <last_update_submitted>February 8, 2019</last_update_submitted>
  <last_update_submitted_qc>February 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Calcium heparin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Edoxaban</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/daiichi-sankyo/</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>From September 2012 through January 2014, a total of 85 patients were enrolled at 26 centers in North America (US and Canada). One subject was not included in either the full analysis set or the safety analysis set because of major protocol violation - he did not take any dose of study drug.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Edoxaban</title>
          <description>Participants treated with edoxaban</description>
        </group>
        <group group_id="P2">
          <title>Warfarin</title>
          <description>Participants treated with warfarin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="56"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Edoxaban</title>
          <description>Participants treated with edoxaban</description>
        </group>
        <group group_id="B2">
          <title>Warfarin</title>
          <description>Participants treated with warfarin</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="56"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="84"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Relative Change From Baseline in Thrombus Volume Assessed by MRI [Using the Magnetic Resonance Venography (MRV) Method]</title>
        <description>Thrombus Volume (mm^3) was measured at baseline and between days 14 to 21 using MRI results as determined by Magnetic Resonance Venography (MRV) method, and the relative percentage change from baseline was calculated</description>
        <time_frame>Baseline to final visit (Day 14-21)</time_frame>
        <population>Modified intention to treat (mITT), defined as intention to treat minus the one patient who did not take the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>Edoxaban</title>
            <description>Participants treated with edoxaban</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Participants treated with warfarin</description>
          </group>
        </group_list>
        <measure>
          <title>Relative Change From Baseline in Thrombus Volume Assessed by MRI [Using the Magnetic Resonance Venography (MRV) Method]</title>
          <description>Thrombus Volume (mm^3) was measured at baseline and between days 14 to 21 using MRI results as determined by Magnetic Resonance Venography (MRV) method, and the relative percentage change from baseline was calculated</description>
          <population>Modified intention to treat (mITT), defined as intention to treat minus the one patient who did not take the investigational product</population>
          <units>percentage of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-46.6" spread="45.53"/>
                    <measurement group_id="O2" value="-51.4" spread="32.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>8.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.74</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.7</ci_lower_limit>
            <ci_upper_limit>30.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Relevant Bleeding</title>
        <description>Clinically relevant bleeding was defined as major or clinically relevant non-major bleeding</description>
        <time_frame>Initial dose of study drug up to 3 days after last dose</time_frame>
        <population>Adjudicated in the mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Edoxaban</title>
            <description>Participants treated with edoxaban</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Participants treated with warfarin</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Relevant Bleeding</title>
          <description>Clinically relevant bleeding was defined as major or clinically relevant non-major bleeding</description>
          <population>Adjudicated in the mITT population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Recurrence of Venous Thromboembolism (VTE)</title>
        <description>Number of participants with investigator-confirmed recurrent VTE events that start or worsen after the first dose of study drug and prior to the date of the final visit or telephone contact (inclusive)</description>
        <time_frame>Baseline to final visit (Day 14-21)</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Edoxaban</title>
            <description>Participants treated with edoxaban</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Participants treated with warfarin</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Recurrence of Venous Thromboembolism (VTE)</title>
          <description>Number of participants with investigator-confirmed recurrent VTE events that start or worsen after the first dose of study drug and prior to the date of the final visit or telephone contact (inclusive)</description>
          <population>mITT</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Major Adverse Cardiovascular Events (MACE)</title>
        <description>MACE is defined as a composite of non-fatal myocardial infarction (MI), non-fatal stroke, non-fatal systemic embolic event (SEE) and cardiovascular death</description>
        <time_frame>Initial dose of study drug up to 3 days after last dose</time_frame>
        <population>Adjudicated confirmed events in the mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Edoxaban</title>
            <description>Participants treated with edoxaban</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Participants treated with warfarin</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Major Adverse Cardiovascular Events (MACE)</title>
          <description>MACE is defined as a composite of non-fatal myocardial infarction (MI), non-fatal stroke, non-fatal systemic embolic event (SEE) and cardiovascular death</description>
          <population>Adjudicated confirmed events in the mITT population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Change From Baseline in the Presence or Absence of Thrombus by Vessel</title>
        <time_frame>Baseline to final visit (Day 14-21)</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Edoxaban</title>
            <description>Participants treated with edoxaban</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Participants treated with warfarin</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Change From Baseline in the Presence or Absence of Thrombus by Vessel</title>
          <population>mITT</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Edoxaban</title>
          <description>Participants treated with edoxaban</description>
        </group>
        <group group_id="E2">
          <title>Warfarin</title>
          <description>Participants treated with warfarin</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 14.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title vocab="14.0">Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title vocab="14.0">Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title vocab="14.0">Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 14.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypocoagulable state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Atrioventricular block second degree</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Mitral valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title vocab="14.0">Tricuspid valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Diverticulum intestinal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Epigastric discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastric polyps</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Loose tooth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic steatosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title vocab="14.0">Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Infected skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Arthopod bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Contrast media reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Post procedural swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Procedural nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Epstein-Barr virus antibody positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vitamin B12 deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscle fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscle tightness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Limb discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title vocab="14.0">Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lung neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Metastases to liver</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Metastases to lung</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Neuritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal cyst</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prostatomegaly</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Skln ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lymphoedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Post thrombotic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Director, CVM TA Development</name_or_title>
      <organization>Daiichi Sankyo, Inc.</organization>
      <phone>732-590-5000</phone>
    </point_of_contact>
  </clinical_results>
</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/NCT01662908
org study id: DU176b-D-U211
nct id: NCT01662908
lead sponsor: 
has dmc: No
Assess the relative change in thrombus volume as determined by two assessments (Baseline and
      Day 14-21) with magnetic resonance venography (MRV) in subjects with deep-vein thrombosis
      (DVT) treated with either an edoxaban monotherapy regimen or a low molecular weight (LMW)
      heparin/warfarin regimen.
The classical management of patients with venous thromboembolism (VTE) consists of an initial
      treatment of at least five days of a (LMW) heparin followed by long-term treatment with a
      vitamin K antagonist (VKA), such as warfarin. The eTRIS study will address the clinically
      important question of whether edoxaban monotherapy, without concomitant (LMW) heparin at the
      time of treatment initiation is comparable to or better than standard treatment with (LMW)
      heparin/warfarin therapy in subjects with acute symptomatic DVT as assessed by the relative
      change from baseline in thrombus volume (measured by MRI) at Day 14-21.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Relative Change From Baseline in Thrombus Volume Assessed by MRI [Using the Magnetic Resonance Venography (MRV) Method]
time frame: Baseline to final visit (Day 14-21)
description: Thrombus Volume (mm^3) was measured at baseline and between days 14 to 21 using MRI results as determined by Magnetic Resonance Venography (MRV) method, and the relative percentage change from baseline was calculated
measure: Number of Participants With Clinically Relevant Bleeding
time frame: Initial dose of study drug up to 3 days after last dose
description: Clinically relevant bleeding was defined as major or clinically relevant non-major bleeding
measure: Number of Participants With Recurrence of Venous Thromboembolism (VTE)
time frame: Baseline to final visit (Day 14-21)
description: Number of participants with investigator-confirmed recurrent VTE events that start or worsen after the first dose of study drug and prior to the date of the final visit or telephone contact (inclusive)
measure: Number of Participants With Major Adverse Cardiovascular Events (MACE)
time frame: Initial dose of study drug up to 3 days after last dose
description: MACE is defined as a composite of non-fatal myocardial infarction (MI), non-fatal stroke, non-fatal systemic embolic event (SEE) and cardiovascular death
measure: Number of Participants With Change From Baseline in the Presence or Absence of Thrombus by Vessel
time frame: Baseline to final visit (Day 14-21)
arm group label: edoxaban tosylate
arm group type: Experimental
arm group label: heparin/warfarin
arm group type: Active Comparator
intervention type: Drug
intervention name: edoxaban tosylate
description: edoxaban tosylate (DU-176b), film-coated for oral use, 90 mg once daily (QD) for 10 days (±2 days) followed by 60 mg QD for a total of approximately 90 days of edoxaban treatment
arm group label: edoxaban tosylate
intervention type: Drug
intervention name: enoxaparin/unfractionated heparin
description: enoxaparin - administered by subcutaneous injection;1 mg/kg/ twice daily or 1.5 mg/kg once daily unfractionated heparin - started with 5000 IU bolus intravenous administration, 1300 IU/h continuous infusion, minimum of 5 days of treatment and stopped when target INR (2.0 - 3.0) is achieved.
arm group label: heparin/warfarin
intervention type: Drug
intervention name: warfarin
description: tablet for oral use; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; 90 days treatment.
arm group label: heparin/warfarin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Samuel Z Goldhaber, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Heparin
mesh term: Enoxaparin
mesh term: Calcium heparin
mesh term: Warfarin
mesh term: Edoxaban
sharing ipd: Yes
ipd description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
ipd access criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
ipd url: https://vivli.org/ourmember/daiichi-sankyo/
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