<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/NCT04489849</url>
  </required_header>
  <id_info>
    <org_study_id>108-029-F</org_study_id>
    <nct_id>NCT04489849</nct_id>
  </id_info>
  <brief_title>Apixaban for Prevention of Post-angioplasty Thrombosis of Hemodialysis Vascular Access</brief_title>
  <official_title>Apixaban for Prevention of Post-angioplasty Thrombosis of Hemodialysis Vascular Access</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital Hsin-Chu Branch</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital Hsin-Chu Branch</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Taiwan was among the countries with high prevalence of end stage renal disease (ESRD), and&#xD;
      more than 90% of ESRD patients in Taiwan received hemodialysis. Thrombosis are the most&#xD;
      common complications of hemodialysis vascular access, with an annual incidence of 30-65% for&#xD;
      dialysis grafts. Although endovascular thrombectomy is effective and convenient, the&#xD;
      recurrence rate was high, nearly 50% in three months.&#xD;
&#xD;
      The mechanisms of dialysis vascular access thrombosis were multi-factorial, including flow&#xD;
      stasis, endothelial injury and hypercoagulability. Our recent study showed that 63% of&#xD;
      patients with early thrombosis after angioplasty had at least one thrombophilic factor.&#xD;
      Nonetheless, no antithrombotic regimen has been validated to be effective for prevention of&#xD;
      thrombosis, either primary or secondary prevention. Novel oral anticoagulants (NOACs) have&#xD;
      shown comparable efficacy as VKA with significant decrease in major bleeding. Furthermore,&#xD;
      NOACs have the advantage of rapid onset without the need for titration, which should be more&#xD;
      effective in the critical period early after thrombectomy. NOAC have almost replaced the role&#xD;
      of VKA for the prevention of stroke in patients with atrial fibrillation. They also replaced&#xD;
      oral and parenteral anticoagulants in the treatment and prevention of deep vein thrombosis.&#xD;
      Among the 4 available NOACs today, only apixaban had received approval by the US Food and&#xD;
      Drug Administration (FDA) to be used in patients with ESRD for stroke prevention in atrial&#xD;
      fibrillation.&#xD;
&#xD;
      In consideration of the trade-off between thrombotic and bleeding risk, we aimed at secondary&#xD;
      prevention for patients with a thrombosis event after a successful thrombectomy procedure.&#xD;
      Apixaban would be used because it was approved by FDA for the use of hemodialysis patients,&#xD;
      with a risk of major bleeding of 5% for 3 months. Furthermore, considering the ethnic (Asia&#xD;
      population) and clinical (ESRD and high bleeding risk) background of our target population,&#xD;
      2.5 mg twice daily dose was chosen in this study to minimize the bleeding risk. This study is&#xD;
      a multi-center, prospective, open-labeled, randomized trial with blinded evaluation of all&#xD;
      outcomes (PROBE design). We anticipated to enroll 150 patients, with 1:1 randomization to&#xD;
      apixaban and control group (no antithrombotic agent). The duration of therapy will be 3&#xD;
      months and the primary outcome is the time to recurrent thrombotic event. Secondary outcomes&#xD;
      included frequency of thrombosis, repeat interventions, and bleeding events. We hypothesized&#xD;
      that apixaban could prolong the thrombosis-free interval after a successful thrombectomy&#xD;
      procedure of hemodialysis vascular access.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 14, 2020</start_date>
  <completion_date type="Anticipated">June 14, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 14, 2022</primary_completion_date>
  <phase>Phase 4</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>Thrombosis rate</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of thrombosis</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of angioplasty for vascular access</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major bleeding event</measure>
    <time_frame>3 months</time_frame>
    <description>Major bleeding according to BARC2 criteria</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Hemodialysis Access Failure</condition>
  <arm_group>
    <arm_group_label>Apixaban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apixaban 2.5mg BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Other treatment except oral anticoagulant</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban 2.5 MG</intervention_name>
    <description>apixaban 2.5mg BID for 3 months in experimental group</description>
    <arm_group_label>Apixaban</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Active Control</intervention_name>
    <description>Medication other than anticoagulation</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 20-99 years old&#xD;
&#xD;
          -  End stage renal disease, patients on maintenance hemodialysis for at least one month&#xD;
&#xD;
          -  Dialysis vascular access thrombosis, documented by angiograph, and thrombosis was&#xD;
             salvaged by endovascular or surgical procedures successfully&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of intracranial hemorrhage&#xD;
&#xD;
          -  Major bleeding in recent 3 months, which defined as Bleeding Academic Research&#xD;
             Consortium (BARC) 2 criteria&#xD;
&#xD;
          -  Concomitant use of dual antiplatelet agent (aspirin and clopidogrel)&#xD;
&#xD;
          -  Concomitant use of ticagrelor&#xD;
&#xD;
          -  Concomitant use of warfarin&#xD;
&#xD;
          -  Planned to receive surgery in recent 3 months&#xD;
&#xD;
          -  Planned to receive coronary stents in recent 3 months&#xD;
&#xD;
          -  Hemoglobin &lt; 7.0 g/dL or Platelet count &lt; 80 K/uL&#xD;
&#xD;
          -  Moderate or severe liver dysfunction, defined as Child-Pugh score &gt; 6&#xD;
&#xD;
          -  Patient received bioprosthetic or mechanical heart valve&#xD;
&#xD;
          -  Cannot signed informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Tsung-Yu Ko, MD</last_name>
    <phone>03-5326151</phone>
    <email>sonicwind1022@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>TsungYu Ko, MD</last_name>
    <phone>03-5326151</phone>
    <email>sonicwind1022@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Hospital HsinChu branch</name>
      <address>
        <city>Hsinchu</city>
        <zip>300</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>NienChu Kui</last_name>
      <email>hch01215@hch.gov.tw</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital,HsinChu branch</name>
      <address>
        <city>Hsinchu</city>
        <zip>300</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>NienChu Kui</last_name>
      <email>hch01215@hch.gov.tw</email>
    </contact>
    <investigator>
      <last_name>Tsung-Yu Ko, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chih-Cheng Wu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apixaban</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04489849
org study id: 108-029-F
nct id: NCT04489849
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Taiwan was among the countries with high prevalence of end stage renal disease (ESRD), and
      more than 90% of ESRD patients in Taiwan received hemodialysis. Thrombosis are the most
      common complications of hemodialysis vascular access, with an annual incidence of 30-65% for
      dialysis grafts. Although endovascular thrombectomy is effective and convenient, the
      recurrence rate was high, nearly 50% in three months.

      The mechanisms of dialysis vascular access thrombosis were multi-factorial, including flow
      stasis, endothelial injury and hypercoagulability. Our recent study showed that 63% of
      patients with early thrombosis after angioplasty had at least one thrombophilic factor.
      Nonetheless, no antithrombotic regimen has been validated to be effective for prevention of
      thrombosis, either primary or secondary prevention. Novel oral anticoagulants (NOACs) have
      shown comparable efficacy as VKA with significant decrease in major bleeding. Furthermore,
      NOACs have the advantage of rapid onset without the need for titration, which should be more
      effective in the critical period early after thrombectomy. NOAC have almost replaced the role
      of VKA for the prevention of stroke in patients with atrial fibrillation. They also replaced
      oral and parenteral anticoagulants in the treatment and prevention of deep vein thrombosis.
      Among the 4 available NOACs today, only apixaban had received approval by the US Food and
      Drug Administration (FDA) to be used in patients with ESRD for stroke prevention in atrial
      fibrillation.

      In consideration of the trade-off between thrombotic and bleeding risk, we aimed at secondary
      prevention for patients with a thrombosis event after a successful thrombectomy procedure.
      Apixaban would be used because it was approved by FDA for the use of hemodialysis patients,
      with a risk of major bleeding of 5% for 3 months. Furthermore, considering the ethnic (Asia
      population) and clinical (ESRD and high bleeding risk) background of our target population,
      2.5 mg twice daily dose was chosen in this study to minimize the bleeding risk. This study is
      a multi-center, prospective, open-labeled, randomized trial with blinded evaluation of all
      outcomes (PROBE design). We anticipated to enroll 150 patients, with 1:1 randomization to
      apixaban and control group (no antithrombotic agent). The duration of therapy will be 3
      months and the primary outcome is the time to recurrent thrombotic event. Secondary outcomes
      included frequency of thrombosis, repeat interventions, and bleeding events. We hypothesized
      that apixaban could prolong the thrombosis-free interval after a successful thrombectomy
      procedure of hemodialysis vascular access.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Thrombosis rate
time frame: 3 months
measure: Frequency of thrombosis
time frame: 3 months
measure: Frequency of angioplasty for vascular access
time frame: 3 months
measure: Major bleeding event
time frame: 3 months
description: Major bleeding according to BARC2 criteria
arm group label: Apixaban
arm group type: Experimental
description: Apixaban 2.5mg BID
arm group label: Control
arm group type: Active Comparator
description: Other treatment except oral anticoagulant
intervention type: Drug
intervention name: Apixaban 2.5 MG
description: apixaban 2.5mg BID for 3 months in experimental group
arm group label: Apixaban
intervention type: Other
intervention name: Active Control
description: Medication other than anticoagulation
arm group label: Control
criteria: 
gender: All
minimum age: 20 Years
maximum age: 99 Years
healthy volunteers: No
last name: Tsung-Yu Ko, MD
phone: 03-5326151
email: sonicwind1022@gmail.com
last name: TsungYu Ko, MD
phone: 03-5326151
email: sonicwind1022@gmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Thrombosis
mesh term: Apixaban
sharing ipd: No