<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/NCT01708850</url>
  </required_header>
  <id_info>
    <org_study_id>Catheter 2</org_study_id>
    <nct_id>NCT01708850</nct_id>
  </id_info>
  <brief_title>Study in Cancer Patients With Central Line Associated Clots in the Upper Extremity Treated With Rivaroxaban (Catheter 2)</brief_title>
  <official_title>A Pilot Study in Cancer Patients With Central Venous Catheter Associated Deep Vein Thrombosis in the Upper Extremity Treated With Rivaroxaban (Catheter 2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>London Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>London Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with cancer and an upper extremity DVT associated with a central venous catheter&#xD;
      (CVC) will receive rivaroxaban. CVC survival will be assessed and compared to previous rates&#xD;
      with low molecular weight heparin (LMWH) and warfarin, along with secondary safety outcomes&#xD;
      including bleeding and recurrent venous thromboembolism.&#xD;
&#xD;
      The investigators hypothesize that anticoagulation with rivaroxaban in patients with UEDVT&#xD;
      secondary to central venous catheters in patients with active malignancy is an effective&#xD;
      therapy as quantified by the success of catheter preservation. Prolonged line salvage rate&#xD;
      without recurrence of UEDVT will improve the management of cancer patients who develop an&#xD;
      upper extremity deep venous thrombosis in the setting of a central venous catheter.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a prospective cohort study of patients who present with an acute upper limb&#xD;
      thrombosis in the setting of a central venous catheter. The total study duration will be 12&#xD;
      weeks, with one follow up telephone visit at 6 months. All patients will be treated with&#xD;
      rivaroxaban at a dose of 15 mg orally twice daily for three weeks, followed by 20 mg daily.&#xD;
      Anticoagulation will continue for three months regardless of the length of time the catheter&#xD;
      is in place. Continuation of anticoagulation beyond this time period is at the discretion of&#xD;
      the investigators.&#xD;
&#xD;
      Strengths of this study include its prospective cohort format, and access to a large&#xD;
      oncologic population through the London Regional Cancer Program and other corresponding&#xD;
      centres. In addition, The Catheter Study looking at CVC survival and safety in patients with&#xD;
      cancer diagnosed with UEDVT and treated with a bridging protocol of warfarin/dalteparin was&#xD;
      organized primarily through the LHSc and results therein could be directly compared to the&#xD;
      results from this study given the similar patient population.&#xD;
&#xD;
      Limitations of this study include the small sample size and the fact that there is no LMWH&#xD;
      monotherapy comparison group. In addition, this will be an open study with no blinding, given&#xD;
      the nature of line survival. There is also the chance that a proportion of patients will have&#xD;
      their catheters removed for other reasons, such as finishing treatment or personal&#xD;
      preference, which could affect the validity of survival results.&#xD;
&#xD;
      This design was selected given the small number of patients presenting with this diagnosis&#xD;
      each year at our centre, which would present difficulty in accruing enough patients for&#xD;
      several comparisons group. Results will be compared to the Catheter Study and previous&#xD;
      literature.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of central line failure, defined as infusion failure that does not respond to 2mg tPA.</measure>
    <time_frame>12 weeks</time_frame>
    <description>The primary endpoint of the study will be proportion of central line failure, defined as infusion failure that does not respond to 2mg tPA, within the 3 months of study follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence of DVT or PE</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major Bleeding</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically Relevant Non-Major Bleeding</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Central Line Failure</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Neoplasm</condition>
  <condition>Central Venous Catheter Thrombosis</condition>
  <arm_group>
    <arm_group_label>Rivaroxaban</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Rivaroxaban 15 mg po bid x 3 weeks, followed by rivaroxaban 20 mg po daily x 9 weeks. Then up to discretion of investigator to decide regarding further anticoagulation as study length is limited to 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivaroxaban</intervention_name>
    <description>All specified in arm description. One arm study.</description>
    <arm_group_label>Rivaroxaban</arm_group_label>
    <other_name>Xarelto</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female &gt; 18 years of age.&#xD;
&#xD;
          2. Symptomatic acute upper limb thrombosis in the axillary, subclavian, innominate or&#xD;
             internal jugular veins, with or without pulmonary embolism, associated with central&#xD;
             venous catheter objectively documented by compression ultrasonography, venogram or CT&#xD;
             scan.&#xD;
&#xD;
          3. Diagnosis of active malignancy (other than non-melanoma skin cancer), defined as&#xD;
             patients who are either receiving active treatment, or have metastatic disease or who&#xD;
             have been diagnosed within the past two years.&#xD;
&#xD;
          4. Willing to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Dialysis catheters.&#xD;
&#xD;
          2. Active bleeding or high risk for major bleeding.&#xD;
&#xD;
          3. Platelet Count &lt; 75 x 109/L.&#xD;
&#xD;
          4. Creatinine Clearance &lt; 30 mL/min.&#xD;
&#xD;
          5. Currently on other anticoagulant with therapeutic intent for another indication.*&#xD;
&#xD;
          6. Pulmonary embolism accompanied by hemodynamic instability or oxygen requirement.&#xD;
&#xD;
          7. Inability to infuse through the catheter after a trial of intraluminal thrombolytic&#xD;
             therapy (ie. 2 mg tPA).&#xD;
&#xD;
          8. Patients with AML, ALL or multiple myeloma with a bone marrow or stem cell transplant&#xD;
             planned within the next 3 months.&#xD;
&#xD;
          9. Thrombosis involving the brachial or cephalic veins only.&#xD;
&#xD;
         10. Treatment for current episode &gt; 7 days with any acceptable anticoagulant therapy.&#xD;
&#xD;
         11. Concomitant use of P-glycoprotein and CYP3A4 inhibitors (ie. azole antifungals such as&#xD;
             ketoconazole) or inducers (ie. rifampicin, antiepileptics).*&#xD;
&#xD;
         12. Recent coronary artery stent requiring dual anti-platelet therapy.&#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>Dr. Michael J. Kovacs, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>London Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A5W9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Kovacs MJ, Kahn SR, Rodger M, Anderson DR, Andreou R, Mangel JE, Morrow B, Clement AM, Wells PS. A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without catheter removal for the treatment of upper extremity deep vein thrombosis (The Catheter Study). J Thromb Haemost. 2007 Aug;5(8):1650-3. doi: 10.1111/j.1538-7836.2007.02613.x. Epub 2007 May 7.</citation>
    <PMID>17488349</PMID>
  </reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 17, 2012</study_first_posted>
  <last_update_submitted>September 6, 2016</last_update_submitted>
  <last_update_submitted_qc>September 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>London Health Sciences Centre</investigator_affiliation>
    <investigator_full_name>Gwynivere Davies</investigator_full_name>
    <investigator_title>Resident Researcher (Principal Investigator: Dr. Michael Kovacs</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Upper Extremity Deep Vein Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rivaroxaban</mesh_term>
  </intervention_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/NCT01708850
org study id: Catheter 2
nct id: NCT01708850
lead sponsor: 
has dmc: No
Patients with cancer and an upper extremity DVT associated with a central venous catheter
      (CVC) will receive rivaroxaban. CVC survival will be assessed and compared to previous rates
      with low molecular weight heparin (LMWH) and warfarin, along with secondary safety outcomes
      including bleeding and recurrent venous thromboembolism.

      The investigators hypothesize that anticoagulation with rivaroxaban in patients with UEDVT
      secondary to central venous catheters in patients with active malignancy is an effective
      therapy as quantified by the success of catheter preservation. Prolonged line salvage rate
      without recurrence of UEDVT will improve the management of cancer patients who develop an
      upper extremity deep venous thrombosis in the setting of a central venous catheter.
This will be a prospective cohort study of patients who present with an acute upper limb
      thrombosis in the setting of a central venous catheter. The total study duration will be 12
      weeks, with one follow up telephone visit at 6 months. All patients will be treated with
      rivaroxaban at a dose of 15 mg orally twice daily for three weeks, followed by 20 mg daily.
      Anticoagulation will continue for three months regardless of the length of time the catheter
      is in place. Continuation of anticoagulation beyond this time period is at the discretion of
      the investigators.

      Strengths of this study include its prospective cohort format, and access to a large
      oncologic population through the London Regional Cancer Program and other corresponding
      centres. In addition, The Catheter Study looking at CVC survival and safety in patients with
      cancer diagnosed with UEDVT and treated with a bridging protocol of warfarin/dalteparin was
      organized primarily through the LHSc and results therein could be directly compared to the
      results from this study given the similar patient population.

      Limitations of this study include the small sample size and the fact that there is no LMWH
      monotherapy comparison group. In addition, this will be an open study with no blinding, given
      the nature of line survival. There is also the chance that a proportion of patients will have
      their catheters removed for other reasons, such as finishing treatment or personal
      preference, which could affect the validity of survival results.

      This design was selected given the small number of patients presenting with this diagnosis
      each year at our centre, which would present difficulty in accruing enough patients for
      several comparisons group. Results will be compared to the Catheter Study and previous
      literature.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of central line failure, defined as infusion failure that does not respond to 2mg tPA.
time frame: 12 weeks
description: The primary endpoint of the study will be proportion of central line failure, defined as infusion failure that does not respond to 2mg tPA, within the 3 months of study follow-up.
measure: Recurrence of DVT or PE
time frame: 12 weeks
measure: Major Bleeding
time frame: 12 weeks
measure: Clinically Relevant Non-Major Bleeding
time frame: 12 weeks
measure: Death
time frame: 12 weeks
measure: Time to Central Line Failure
time frame: 12 weeks
arm group label: Rivaroxaban
arm group type: Other
description: Rivaroxaban 15 mg po bid x 3 weeks, followed by rivaroxaban 20 mg po daily x 9 weeks. Then up to discretion of investigator to decide regarding further anticoagulation as study length is limited to 12 weeks.
intervention type: Drug
intervention name: Rivaroxaban
description: All specified in arm description. One arm study.
arm group label: Rivaroxaban
other name: Xarelto
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dr. Michael J. Kovacs, MD, FRCPC
role: Principal Investigator
affiliation: London Health Sciences Centre
facility: 
country: Canada
citation: Kovacs MJ, Kahn SR, Rodger M, Anderson DR, Andreou R, Mangel JE, Morrow B, Clement AM, Wells PS. A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without catheter removal for the treatment of upper extremity deep vein thrombosis (The Catheter Study). J Thromb Haemost. 2007 Aug;5(8):1650-3. doi: 10.1111/j.1538-7836.2007.02613.x. Epub 2007 May 7.
PMID: 17488349
responsible party type: Principal Investigator
investigator affiliation: London Health Sciences Centre
investigator full name: Gwynivere Davies
investigator title: Resident Researcher (Principal Investigator: Dr. Michael Kovacs
mesh term: Thrombosis
mesh term: Upper Extremity Deep Vein Thrombosis
mesh term: Rivaroxaban