<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/NCT02227368</url>
  </required_header>
  <id_info>
    <org_study_id>D5135L00003</org_study_id>
    <nct_id>NCT02227368</nct_id>
  </id_info>
  <brief_title>Walking Effect of Long Term Ticagrelor in Subjects With PAD Who Have Undergone EVR</brief_title>
  <acronym>TI-PAD EVR</acronym>
  <official_title>A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients With Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CPC Clinical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the effect of ticagrelor versus aspirin on the change in peak walking time,&#xD;
      evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in&#xD;
      patients with peripheral artery disease who have undergone endovascular revascularization for&#xD;
      moderate to severe claudication or ischemic rest pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to&#xD;
      Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin&#xD;
      Administration in Ambulatory Patients with Peripheral Artery Disease Undergoing Endovascular&#xD;
      Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular&#xD;
      Revascularization Study TI-PAD I EVR.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">October 20, 2014</start_date>
  <completion_date type="Actual">May 23, 2016</completion_date>
  <primary_completion_date type="Actual">May 23, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)</measure>
    <time_frame>26 Weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)</measure>
    <time_frame>26 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Peripheral Artery Disease (PAD)</condition>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>26 Weeks of ticagrelor 90mg twice a day plus aspirin placebo once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>26 Weeks of aspirin 100mg once daily plus ticagrelor placebo twice a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor</intervention_name>
    <description>Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.</description>
    <arm_group_label>Ticagrelor</arm_group_label>
    <other_name>Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Comparator</intervention_name>
    <description>Aspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures</description>
    <arm_group_label>Aspirin</arm_group_label>
    <other_name>Aspirin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Written informed consent prior to any study specific procedures.&#xD;
&#xD;
          2. Ambulatory male or female outpatients aged 50 years of age or older at the time of the&#xD;
             Screening Visit.&#xD;
&#xD;
          3. EVR, below the inguinal ligament that includes the distal SFA and/or popliteal and/or&#xD;
             tibial arteries, that is planned to occur within 5 weeks after the Screening Visit, as&#xD;
             determined and clearly documented by the Principal Investigator or physician&#xD;
             Sub-Investigator (MD/DO). Patients undergoing a proximal revascularization may be&#xD;
             enrolled as long as their procedure also includes treating the distal SFA, popliteal&#xD;
             or tibial arteries. The EVR must be confirmed as technically successful (a completed&#xD;
             procedure where haemostasis has been achieved) before the patient is randomised.&#xD;
&#xD;
          4. Normal inflow into the lower extremity as determined by the Principal Investigator or&#xD;
             physician Sub-Investigator (MD/DO). Adequacy of inflow can be assessed by hemodynamic&#xD;
             measures, angiography or other imaging modalities obtained during Screening or&#xD;
             recorded in the medical records up to 30 days prior to the Screening Visit or as&#xD;
             defined by imaging at the time of the procedure. A patient with inadequate inflow at&#xD;
             the time of Screening can still be enrolled if the inflow is addressed and resolved by&#xD;
             the planned revascularization procedure.&#xD;
&#xD;
          5. Diagnosis of PAD confirmed by history and any one of the following observed in the&#xD;
             index (intervention) leg at the Screening Visit:&#xD;
&#xD;
               1. Resting ABI ≤0.90, or&#xD;
&#xD;
               2. In patients with an ABI &gt; 1.40 (non-compressible vessels) a resting GTI &lt;0.70 can&#xD;
                  be used for inclusions.&#xD;
&#xD;
          6. Patient has been advised of the beneficial effects of smoking cessation and exercise&#xD;
             therapy but is not in the process of changing their smoking status or exercise at the&#xD;
             time of the Screening Visit.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site).&#xD;
&#xD;
          2. Revascularisation planned only to treat proximal (inflow) disease in the iliac and/or&#xD;
             common femoral arteries.&#xD;
&#xD;
          3. Previous randomisation in the present study.&#xD;
&#xD;
          4. Participation in another clinical study with an investigational product within the&#xD;
             last 3 months or any new clinical trial during the course of this study.&#xD;
&#xD;
          5. Gangrene or ischemic ulcer of either lower extremity.&#xD;
&#xD;
          6. PAD of a non-atherosclerotic nature.&#xD;
&#xD;
          7. Clinical necessity to use dual antiplatelet therapy within 7 days prior to&#xD;
             randomisation, or single anti-platelet therapy (ticlopidine, prasugrel, vorapaxar,&#xD;
             ticagrelor or dipyridamole) other than clopidogrel or aspirin. Clopidogrel or aspirin&#xD;
             can be taken up to and including the time that the loading dose is being given.&#xD;
&#xD;
          8. Clinical necessity to use the following restricted concomitant medications within 4&#xD;
             weeks prior to randomisation. Patients taking any of these medications at the&#xD;
             Screening Visit may be considered for randomisation after a 4 week washout period from&#xD;
             the medication.&#xD;
&#xD;
               1. Pentoxifylline or cilostazol for relief of claudication symptoms&#xD;
&#xD;
               2. Chronic oral or parenteral anticoagulant therapy (greater than 7 days)&#xD;
&#xD;
               3. Strong inhibitors of CYP3A enzymes (Section 5.6.9.1)&#xD;
&#xD;
               4. Strong inducers of CYP3A enzymes (Section 5.6.9.2)&#xD;
&#xD;
               5. Simvastatin or lovastatin at daily doses over 40 mg&#xD;
&#xD;
          9. Any disease process (e.g. angina, cardiac abnormality, congestive heart failure (CHF),&#xD;
             chronic obstructive pulmonary disease (COPD), respiratory disease, obesity, stroke,&#xD;
             severe neuropathy of the foot, symptomatic musculoskeletal disease of the lower&#xD;
             extremity), other than PAD, that would interfere with exercise performance during the&#xD;
             ETT or prevent the patient from reaching their claudication-limited PWT as the primary&#xD;
             endpoint of the study.&#xD;
&#xD;
         10. Coronary, aortic surgery, angioplasty, lumbar sympathectomy or lower extremity surgery&#xD;
             that impacts the ability to walk on a treadmill within the past 3 months prior to EVR.&#xD;
             Revascularization of the non-index lower extremity within the past 4 weeks prior to&#xD;
             EVR.&#xD;
&#xD;
         11. Any major lower limb amputation due to PAD anticipated within the next 3 months or&#xD;
             prior major amputation due to PAD (minor toe amputations allowed if it does not&#xD;
             interfere with ambulation).&#xD;
&#xD;
         12. Myocardial infarction or stroke in the previous 3 months.&#xD;
&#xD;
         13. Any concomitant disease process with a life expectancy of less than 1 year or which is&#xD;
             sufficiently severe as to compromise the validity of test performance.&#xD;
&#xD;
         14. Dementia likely to jeopardise understanding of information pertinent to study conduct&#xD;
             or compliance to study procedures.&#xD;
&#xD;
         15. Concern for the inability of the patient to comply with study procedures and/or&#xD;
             followup (e.g., alcohol or drug abuse).&#xD;
&#xD;
         16. Resting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥95 mmHg at the&#xD;
             Screening Visit, in spite of antihypertensive treatments allowed by the protocol.&#xD;
&#xD;
         17. A known bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding,&#xD;
             whether resolved or ongoing.&#xD;
&#xD;
         18. Known severe liver disease (e.g., ascites and or clinical signs of coagulopathy).&#xD;
&#xD;
         19. Renal failure requiring dialysis.&#xD;
&#xD;
         20. History of previous intracranial bleed at any time, gastrointestinal bleed within the&#xD;
             past 6 months, or major surgery within 30 days (if the surgical wound is judged to be&#xD;
             associated with an increased risk of bleeding).&#xD;
&#xD;
         21. History of thrombocytopenia or neutropenia.&#xD;
&#xD;
         22. Hypersensitivity to ticagrelor, aspirin or lactose.&#xD;
&#xD;
         23. Initiation of antidiabetic, antihypertensive, lipid-lowering and beta-blocking drugs&#xD;
             within 1 month prior to the Screening Visit.&#xD;
&#xD;
         24. Pregnancy, lactation, fertility without protection against pregnancy (for women of&#xD;
             childbearing potential; a urine or serum pregnancy test will be performed at the&#xD;
             Screening Visit).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William Hiatt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Colorado Prevention Center Clinical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34471</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Munster</city>
        <state>Indiana</state>
        <zip>46321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yonkers</city>
        <state>New York</state>
        <zip>10701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>McKinney</city>
        <state>Texas</state>
        <zip>75069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <results_first_submitted>May 19, 2017</results_first_submitted>
  <results_first_submitted_qc>May 19, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 14, 2017</results_first_posted>
  <last_update_submitted>June 21, 2017</last_update_submitted>
  <last_update_submitted_qc>June 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Myocardial Infarction</keyword>
  <keyword>Peripheral Arterial disease</keyword>
  <keyword>Mycardial Ischemia</keyword>
  <keyword>Heart Diseases</keyword>
  <keyword>Cardiovascular Diseases</keyword>
  <keyword>Vascular Diseases</keyword>
  <keyword>Altherosclerosis</keyword>
  <keyword>Arteriosclerosis</keyword>
  <keyword>Arterial Occlusive Diseases</keyword>
  <keyword>Peripheral Vascular Diseases</keyword>
  <keyword>Ticagrelor</keyword>
  <keyword>Ticlopidine</keyword>
  <keyword>Platelet Aggregation inhibitors</keyword>
  <keyword>Hematologic Agents</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Purinegic P2Y Receptor Antagonists</keyword>
  <keyword>Purinegic P2 Receptor Antagonists</keyword>
  <keyword>Purinergic Antagonists</keyword>
  <keyword>Purinergic Agents</keyword>
  <keyword>Neurotransmitter Agents</keyword>
  <keyword>Molecular Mechanisms of Pharmacological Actions</keyword>
  <keyword>Physiological Effects of Drugs</keyword>
  <keyword>Fibrinolytic Agents</keyword>
  <keyword>Crardiovascular Agents</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Arterial Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 71 subjects were screened at 16 centers throughout the United States of America (USA).&#xD;
First subject enrolled: 20Oct2014. Last subject last visit: 23May2016. Date of early study termination: 21Oct2015</recruitment_details>
      <pre_assignment_details>A total of 40 subjects were randomised. Thirty-one subjects were not randomised due to not meeting inclusion/exclusion criteria (20 subjects), withdrawing consent prior to randomisation (2 subjects), and other reasons (9 subjects) including not being able to return for randomisation within 48 hours of the qualifying revascularization.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ticagrelor</title>
          <description>Ticagrelor 90mg twice a day plus aspirin placebo once daily</description>
        </group>
        <group group_id="P2">
          <title>Aspirin</title>
          <description>Aspirin 100mg once daily plus ticagrelor placebo twice a day</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Sujects Who Received Treatment</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Sujects Who Completed Treatment</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14">Subjects who discontinued treatment were encouraged to remain in the study.</participants>
                <participants group_id="P2" count="20">Subjects who discontinued treatment were encouraged to remain in the study.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>No EVR/not PAD/PI decision/RLE bypass</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomised subjects with the exception of one subject who did not undergo EVR.</population>
      <group_list>
        <group group_id="B1">
          <title>Ticagrelor</title>
          <description>Ticagrelor 90mg twice a day plus aspirin placebo once daily</description>
        </group>
        <group group_id="B2">
          <title>Aspirin</title>
          <description>Aspirin 100mg once daily plus ticagrelor placebo twice a day</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="16"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.1" spread="9.15"/>
                    <measurement group_id="B2" value="67.0" spread="8.31"/>
                    <measurement group_id="B3" value="67.9" spread="8.60"/>
                  </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="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="34"/>
                  </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>
          <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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="31"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)</title>
        <time_frame>26 Weeks</time_frame>
        <population>ITT population is the analysis population. Six subjects without evaluable baseline were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor</title>
            <description>Ticagrelor 90mg twice a day plus aspirin placebo once daily</description>
          </group>
          <group group_id="O2">
            <title>Aspirin</title>
            <description>Aspirin 100mg once daily plus ticagrelor placebo twice a day</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)</title>
          <population>ITT population is the analysis population. Six subjects without evaluable baseline were excluded from the analysis.</population>
          <units>log(Second)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-0.2" upper_limit="0.2"/>
                    <measurement group_id="O2" value="0.1" lower_limit="-0.0" upper_limit="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3441</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.4</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
            <estimate_desc>Difference is Ticagrelor - Aspirin. LOCF was used for missing data imputation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)</title>
        <time_frame>26 Weeks</time_frame>
        <population>ITT population is the analysis population. Twelve subjects without evaluable baseline were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor</title>
            <description>Ticagrelor 90mg twice a day plus aspirin placebo once daily</description>
          </group>
          <group group_id="O2">
            <title>Aspirin</title>
            <description>Aspirin 100mg once daily plus ticagrelor placebo twice a day</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)</title>
          <population>ITT population is the analysis population. Twelve subjects without evaluable baseline were excluded from the analysis.</population>
          <units>log(Second)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.1" upper_limit="1.1"/>
                    <measurement group_id="O2" value="0.5" lower_limit="0.1" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6186</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.4</ci_lower_limit>
            <ci_upper_limit>0.6</ci_upper_limit>
            <estimate_desc>Difference is Ticagrelor - Aspirin. LOCF was used for missing data imputation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>26 weeks treatment period + 30 days followup</time_frame>
      <desc>Only SAEs and AEs of interest were collected for this study. Treatment Emergent SAEs and Treatment Emergent AEs of interest are reported here.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ticagrelor</title>
          <description>Ticagrelor 90mg twice a day plus aspirin placebo once daily</description>
        </group>
        <group group_id="E2">
          <title>Aspirin</title>
          <description>Aspirin 100mg once daily plus ticagrelor placebo twice a day</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Peripheral artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Version 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </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>The disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can require Confidential Information to be removed and the sponsor can extend the embargo for an additional 90 days.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study was terminated early for low enrolment. Less than 25% of anticipated number of subjects were enroled and there was an imbanlance between groups. Therefore, the results should be interpreted with caution.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Naeem Khan, MD</name_or_title>
      <organization>AstraZeneca Pharmaceuticals LP</organization>
      <phone>+1 302-885-8976</phone>
      <email>Naeem.Khan@astrazeneca.com</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/NCT02227368
org study id: D5135L00003
nct id: NCT02227368
lead sponsor: 
collaborator: 
has dmc: No
To compare the effect of ticagrelor versus aspirin on the change in peak walking time,
      evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in
      patients with peripheral artery disease who have undergone endovascular revascularization for
      moderate to severe claudication or ischemic rest pain.
A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to
      Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin
      Administration in Ambulatory Patients with Peripheral Artery Disease Undergoing Endovascular
      Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular
      Revascularization Study TI-PAD I EVR.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)
time frame: 26 Weeks
measure: Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)
time frame: 26 Weeks
arm group label: Ticagrelor
arm group type: Experimental
description: 26 Weeks of ticagrelor 90mg twice a day plus aspirin placebo once daily
arm group label: Aspirin
arm group type: Active Comparator
description: 26 Weeks of aspirin 100mg once daily plus ticagrelor placebo twice a day
intervention type: Drug
intervention name: Ticagrelor
description: Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.
arm group label: Ticagrelor
other name: Brilinta
intervention type: Drug
intervention name: Comparator
description: Aspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures
arm group label: Aspirin
other name: Aspirin
criteria: 
gender: All
minimum age: 50 Years
maximum age: 130 Years
healthy volunteers: No
last name: William Hiatt, MD
role: Principal Investigator
affiliation: Colorado Prevention Center Clinical Research
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Peripheral Arterial Disease
mesh term: Ticagrelor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study was terminated early for low enrolment. Less than 25% of anticipated number of subjects were enroled and there was an imbanlance between groups. Therefore, the results should be interpreted with caution.
point of contact: 