<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/NCT02260622</url>
  </required_header>
  <id_info>
    <org_study_id>20130484-01H</org_study_id>
    <nct_id>NCT02260622</nct_id>
  </id_info>
  <brief_title>Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia</brief_title>
  <acronym>RIVAL-PAD</acronym>
  <official_title>A Phase 2, Open Label, Pilot Study to Examine the Use of Rivaroxaban Plus Aspirin vs. Clopidogrel Plus Aspirin for the Prevention of Restenosis After Infrainguinal Percutaneous Transluminal Angioplasty for Critical Limb Ischemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Ottawa Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ottawa Hospital Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Up to 10% of patients with peripheral arterial disease (PAD) will develop&#xD;
      critical limb ischemia (CLI) which is a decrease of blood flow in the arteries of the limb.&#xD;
      CLI results in resting pain, ulcers, gangrene, and limb loss. The outcome for patients with&#xD;
      CLI is poor. Within 3 months of onset, 12% of patients will require an amputation (removal of&#xD;
      part of the limb) and 9% will die of major cardiovascular events (heart attack or stroke).&#xD;
      Percutaneous angioplasty (PTA), a procedure used to open the blockages in blood flow, has&#xD;
      become the first-line treatment for CLI given its effectiveness, lower cost, and lower risk&#xD;
      of complications. However, 40% of patients will have re-narrowing of the arteries&#xD;
      (restenosis) following the PTA procedure. This is thought to happen in part due to build up&#xD;
      of blood cells called platelets which can also lead to the formation of blood clots. In order&#xD;
      to try to avoid this problem, most patients are prescribed a combination of two blood&#xD;
      thinning medications, acetylsalicylic acid (ASA or aspirin) and clopidogrel (the brand name&#xD;
      is Plavix).&#xD;
&#xD;
      The purpose of this study is to determine if a new blood thinner called rivaroxaban, given in&#xD;
      combination with aspirin, would be more effective in preventing re-narrowing of the arteries&#xD;
      than the current standard of care (aspirin and clopidogrel).&#xD;
&#xD;
      Rivaroxaban is a pill and does not require blood test monitoring. It has been approved by&#xD;
      Health Canada for use in prevention of blood clots in patients undergoing hip or knee surgery&#xD;
      and to treat patients with blood clots in their legs and lungs. Low dose aspirin has been&#xD;
      approved for reducing the risk of heart attacks and strokes. These medications have not been&#xD;
      tested together in patients for prevention of re-narrowing of their arteries&#xD;
&#xD;
      This is a pilot study conducted at one center, The Ottawa Hospital.&#xD;
&#xD;
      It is a Phase 2 open label randomized controlled trial.&#xD;
&#xD;
      Following the PTA procedure, once all inclusion/exclusion criteria are met, the participant&#xD;
      will be randomized into one of two groups:&#xD;
&#xD;
        1. Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily OR&#xD;
&#xD;
        2. Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
&#xD;
      Visits will occur at 7 days, 30 days, 90 days, 6 months and 12 months. Participants will be&#xD;
      followed for 12 months (± 14 days) in total. All adverse events will be collected for the&#xD;
      duration of the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">June 2017</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reintervention, Above Ankle Amputation and Restenosis (RAS)</measure>
    <time_frame>1 year</time_frame>
    <description>The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With 2 Class Improvement on the Rutherford Scale</measure>
    <time_frame>1 year</time_frame>
    <description>Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.&#xD;
There are seven stages to consider. the lower the score the less severe the disease or condition.&#xD;
Rutherford Scale:&#xD;
Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.&#xD;
Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free Survival</measure>
    <time_frame>1 year</time_frame>
    <description>Event-free survival How long a patient is alive without the need for any further intervention or vascular events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1 year</time_frame>
    <description>Overall survival. How long a patient is alive following the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)</measure>
    <time_frame>1 year</time_frame>
    <description>Target lesion revascularization (TLR) between day 1 and final visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TVR</measure>
    <time_frame>1 year</time_frame>
    <description>Target vessel revascularization (TVR between day 1 and final visit)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peri-procedure Death</measure>
    <time_frame>30 days</time_frame>
    <description>The number of patients that die within 30 days of the revascularization procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MACE</measure>
    <time_frame>1 year</time_frame>
    <description>Cumulative rate of major adverse cardiovascular events between day 1 and final visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major Bleeding</measure>
    <time_frame>90 days</time_frame>
    <description>Cumulative rate of major bleeding between day 1 and day 90</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor Bleeding</measure>
    <time_frame>90 days</time_frame>
    <description>Cumulative clinically relevant or minor bleeding between day 1 and day 90</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>90 days</time_frame>
    <description>Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Critical Limb Ischemia</condition>
  <arm_group>
    <arm_group_label>clopidogrel plus aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rivaroxaban plus aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rivaroxaban plus aspirin</intervention_name>
    <description>Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
    <arm_group_label>rivaroxaban plus aspirin</arm_group_label>
    <other_name>treatment arm</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>clopidogrel plus aspirin</intervention_name>
    <description>Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
    <arm_group_label>clopidogrel plus aspirin</arm_group_label>
    <other_name>Plavix plus ASA</other_name>
    <other_name>Standard Care</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent.&#xD;
&#xD;
          2. Infra-inguinal PAD presenting as CLI defined as a Rutherford category of 3, 4, or 5&#xD;
&#xD;
          3. More than 50% stenosis in the target infrainguinal vessel&#xD;
&#xD;
          4. Good candidates for PTA using POBA (plain old balloon angioplasty) with or without&#xD;
             stenting defined as TASC a and b lesions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Rutherford scale of 0,1,2 or 6&#xD;
&#xD;
          2. Acute limb-threatening ischemia (e.g. embolic disease)&#xD;
&#xD;
          3. Previous infrainguinal bypass or PTA procedures of the affected leg&#xD;
&#xD;
          4. Hybrid procedures&#xD;
&#xD;
          5. Creatinine clearance &lt;30 mL/min&#xD;
&#xD;
          6. Platelet count &lt;100x109/L&#xD;
&#xD;
          7. INR &gt;1.5; Hbg &lt;100 g/L&#xD;
&#xD;
          8. History of or condition associated with increased bleeding risk including, but not&#xD;
             limited to:&#xD;
&#xD;
               1. Major surgical procedure or trauma within 30 days before the randomization visit&#xD;
&#xD;
               2. Clinically significant gastrointestinal bleeding within 6 months before the&#xD;
                  randomization visit&#xD;
&#xD;
               3. History of intracranial, intraocular, spinal, or atraumatic intra-articular&#xD;
                  bleeding&#xD;
&#xD;
               4. Chronic hemorrhagic disorder&#xD;
&#xD;
               5. Known intracranial neoplasm, arteriovenous malformation, or aneurysm&#xD;
&#xD;
               6. Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or&#xD;
                  diastolic blood pressure ≥100 mmHg&#xD;
&#xD;
          9. Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months&#xD;
             or any stroke within 14 days before the randomization visit&#xD;
&#xD;
         10. Aspirin in combination with thienopyridines within 5 days before randomization&#xD;
&#xD;
         11. Intravenous antiplatelets within 5 days before randomization&#xD;
&#xD;
         12. Fibrinolytics within 10 days before randomization&#xD;
&#xD;
         13. Known HIV infection at time of screening&#xD;
&#xD;
         14. Known significant liver disease (e.g., acute clinical hepatitis, chronic active&#xD;
             hepatitis, cirrhosis or ALT &gt;3ULN)&#xD;
&#xD;
         15. Childbearing potential without proper contraceptive measures, pregnancy or breast&#xD;
             feeding&#xD;
&#xD;
         16. Drug addiction or alcohol abuse within 12 months before the randomization visit&#xD;
&#xD;
         17. Systemic treatment with strong CYP 3A4 and P-glycoprotein inhibitors : such as&#xD;
             ketoconazole, itraconazole, posaconazole, or ritonavir&#xD;
&#xD;
         18. Known allergy or hypersensitivity to any component of rivaroxaban, ASA or clopidogrel&#xD;
&#xD;
         19. Need for long term anticoagulation or double antiplatelet agents other than PAD such&#xD;
             as atrial fibrillation, heart valve replacement, acute coronary syndrome, stroke or&#xD;
             venous thromboembolism&#xD;
&#xD;
         20. Anticipated need for chronic (&gt; 4 weeks) therapy with non-steroidal anti-inflammatory&#xD;
             drugs.&#xD;
&#xD;
         21. Concomitant treatment with any other anticoagulant, including oral anticoagulants,&#xD;
             such as warfarin, dabigatran, apixaban, except under circumstances of switching&#xD;
             therapy to or from study treatment.&#xD;
&#xD;
         22. Inability to adhere to protocol.&#xD;
&#xD;
         23. Severe concomitant condition or disease (e.g. life expectancy &lt;6 months secondary to&#xD;
             cancer, advanced liver disease or dementia)&#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>Esteban Gandara, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Hospital Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Prasad Jetty, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Hospital Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <results_first_submitted>November 4, 2019</results_first_submitted>
  <results_first_submitted_qc>November 4, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 22, 2019</results_first_posted>
  <last_update_submitted>November 25, 2019</last_update_submitted>
  <last_update_submitted_qc>November 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Restenosis</keyword>
  <keyword>Critical Limb Ischemia</keyword>
  <keyword>Infrainguinal Percutaneous Transluminal Angioplasty</keyword>
  <keyword>Rivaroxaban</keyword>
  <keyword>Clopidogrel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Limb-Threatening Ischemia</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Rivaroxaban</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 4, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT02260622/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Clopidogrel Plus Aspirin</title>
          <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
        </group>
        <group group_id="P2">
          <title>Rivaroxaban Plus Aspirin</title>
          <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Clopidogrel Plus Aspirin</title>
          <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
        </group>
        <group group_id="B2">
          <title>Rivaroxaban Plus Aspirin</title>
          <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</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="11"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.8" lower_limit="55" upper_limit="84"/>
                    <measurement group_id="B2" value="59.5" lower_limit="54" upper_limit="82"/>
                    <measurement group_id="B3" value="67" lower_limit="54" upper_limit="84"/>
                  </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="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Reintervention, Above Ankle Amputation and Restenosis (RAS)</title>
        <description>The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Reintervention, Above Ankle Amputation and Restenosis (RAS)</title>
          <description>The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With 2 Class Improvement on the Rutherford Scale</title>
        <description>Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.&#xD;
There are seven stages to consider. the lower the score the less severe the disease or condition.&#xD;
Rutherford Scale:&#xD;
Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.&#xD;
Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 2 Class Improvement on the Rutherford Scale</title>
          <description>Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.&#xD;
There are seven stages to consider. the lower the score the less severe the disease or condition.&#xD;
Rutherford Scale:&#xD;
Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.&#xD;
Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Event-free Survival</title>
        <description>Event-free survival How long a patient is alive without the need for any further intervention or vascular events.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival</title>
          <description>Event-free survival How long a patient is alive without the need for any further intervention or vascular events.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival. How long a patient is alive following the intervention.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival. How long a patient is alive following the intervention.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)</title>
        <description>Target lesion revascularization (TLR) between day 1 and final visit</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)</title>
          <description>Target lesion revascularization (TLR) between day 1 and final visit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TVR</title>
        <description>Target vessel revascularization (TVR between day 1 and final visit)</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>TVR</title>
          <description>Target vessel revascularization (TVR between day 1 and final visit)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peri-procedure Death</title>
        <description>The number of patients that die within 30 days of the revascularization procedure.</description>
        <time_frame>30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Peri-procedure Death</title>
          <description>The number of patients that die within 30 days of the revascularization procedure.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </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>
        <type>Secondary</type>
        <title>MACE</title>
        <description>Cumulative rate of major adverse cardiovascular events between day 1 and final visit</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>MACE</title>
          <description>Cumulative rate of major adverse cardiovascular events between day 1 and final visit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </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>
        <type>Secondary</type>
        <title>Major Bleeding</title>
        <description>Cumulative rate of major bleeding between day 1 and day 90</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Major Bleeding</title>
          <description>Cumulative rate of major bleeding between day 1 and day 90</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </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>
        <type>Secondary</type>
        <title>Minor Bleeding</title>
        <description>Cumulative clinically relevant or minor bleeding between day 1 and day 90</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Minor Bleeding</title>
          <description>Cumulative clinically relevant or minor bleeding between day 1 and day 90</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biomarkers</title>
        <description>Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2</description>
        <time_frame>90 days</time_frame>
        <population>Not performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Clopidogrel Plus Aspirin</title>
            <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
          </group>
          <group group_id="O2">
            <title>Rivaroxaban Plus Aspirin</title>
            <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Biomarkers</title>
          <description>Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2</description>
          <population>Not performed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From randomization to 12-month follow-up</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Clopidogrel Plus Aspirin</title>
          <description>Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily&#xD;
clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days</description>
        </group>
        <group group_id="E2">
          <title>Rivaroxaban Plus Aspirin</title>
          <description>Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily&#xD;
rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Minor Bleed - not clinically relevant</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Abnormal Lab Result</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Leg injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </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>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Penny Phillips</name_or_title>
      <organization>Ottawa Hospital Research Institute</organization>
      <phone>613-737-8899</phone>
      <email>pphillips@ohri.ca</email>
    </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/NCT02260622
org study id: 20130484-01H
nct id: NCT02260622
lead sponsor: 
collaborator: 
has dmc: Yes
Background: Up to 10% of patients with peripheral arterial disease (PAD) will develop
      critical limb ischemia (CLI) which is a decrease of blood flow in the arteries of the limb.
      CLI results in resting pain, ulcers, gangrene, and limb loss. The outcome for patients with
      CLI is poor. Within 3 months of onset, 12% of patients will require an amputation (removal of
      part of the limb) and 9% will die of major cardiovascular events (heart attack or stroke).
      Percutaneous angioplasty (PTA), a procedure used to open the blockages in blood flow, has
      become the first-line treatment for CLI given its effectiveness, lower cost, and lower risk
      of complications. However, 40% of patients will have re-narrowing of the arteries
      (restenosis) following the PTA procedure. This is thought to happen in part due to build up
      of blood cells called platelets which can also lead to the formation of blood clots. In order
      to try to avoid this problem, most patients are prescribed a combination of two blood
      thinning medications, acetylsalicylic acid (ASA or aspirin) and clopidogrel (the brand name
      is Plavix).

      The purpose of this study is to determine if a new blood thinner called rivaroxaban, given in
      combination with aspirin, would be more effective in preventing re-narrowing of the arteries
      than the current standard of care (aspirin and clopidogrel).

      Rivaroxaban is a pill and does not require blood test monitoring. It has been approved by
      Health Canada for use in prevention of blood clots in patients undergoing hip or knee surgery
      and to treat patients with blood clots in their legs and lungs. Low dose aspirin has been
      approved for reducing the risk of heart attacks and strokes. These medications have not been
      tested together in patients for prevention of re-narrowing of their arteries

      This is a pilot study conducted at one center, The Ottawa Hospital.

      It is a Phase 2 open label randomized controlled trial.

      Following the PTA procedure, once all inclusion/exclusion criteria are met, the participant
      will be randomized into one of two groups:

        1. Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily OR

        2. Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily

      Visits will occur at 7 days, 30 days, 90 days, 6 months and 12 months. Participants will be
      followed for 12 months (± 14 days) in total. All adverse events will be collected for the
      duration of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Reintervention, Above Ankle Amputation and Restenosis (RAS)
time frame: 1 year
description: The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year
measure: Number of Participants With 2 Class Improvement on the Rutherford Scale
time frame: 1 year
description: Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.
There are seven stages to consider. the lower the score the less severe the disease or condition.
Rutherford Scale:
Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.
Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene
measure: Event-free Survival
time frame: 1 year
description: Event-free survival How long a patient is alive without the need for any further intervention or vascular events.
measure: Overall Survival
time frame: 1 year
description: Overall survival. How long a patient is alive following the intervention.
measure: The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)
time frame: 1 year
description: Target lesion revascularization (TLR) between day 1 and final visit
measure: TVR
time frame: 1 year
description: Target vessel revascularization (TVR between day 1 and final visit)
measure: Peri-procedure Death
time frame: 30 days
description: The number of patients that die within 30 days of the revascularization procedure.
measure: MACE
time frame: 1 year
description: Cumulative rate of major adverse cardiovascular events between day 1 and final visit
measure: Major Bleeding
time frame: 90 days
description: Cumulative rate of major bleeding between day 1 and day 90
measure: Minor Bleeding
time frame: 90 days
description: Cumulative clinically relevant or minor bleeding between day 1 and day 90
measure: Biomarkers
time frame: 90 days
description: Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2
arm group label: clopidogrel plus aspirin
arm group type: Active Comparator
description: Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
arm group label: rivaroxaban plus aspirin
arm group type: Experimental
description: Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily
intervention type: Drug
intervention name: rivaroxaban plus aspirin
description: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
arm group label: rivaroxaban plus aspirin
other name: treatment arm
intervention type: Drug
intervention name: clopidogrel plus aspirin
description: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days
arm group label: clopidogrel plus aspirin
other name: Plavix plus ASA
other name: Standard Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Esteban Gandara, MD
role: Principal Investigator
affiliation: Ottawa Hospital Research Institute
last name: Prasad Jetty, MD
role: Principal Investigator
affiliation: Ottawa Hospital Research Institute
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Chronic Limb-Threatening Ischemia
mesh term: Ischemia
mesh term: Aspirin
mesh term: Rivaroxaban
mesh term: Clopidogrel
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 