<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/NCT02201771</url>
  </required_header>
  <id_info>
    <org_study_id>ISSBRIL0211</org_study_id>
    <nct_id>NCT02201771</nct_id>
  </id_info>
  <brief_title>Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery</brief_title>
  <acronym>DACAB</acronym>
  <official_title>Compare the Efficacy of Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ruijin Hospital</source>
  <brief_summary>
    <textblock>
      The study population will include all patients undergoing elective CABG. Consent and&#xD;
      randomization will occur before surgery. Total 500 patients undergoing elective CABG will be&#xD;
      randomly assigned into three groups with 1:1:1 ratio(167 patients per group) in this&#xD;
      open-label study. All the enrolled patients will stop oral antiplatelet drugs according to&#xD;
      local protocol before the surgery. Within the first 24 hours after surgery, study medication&#xD;
      should be restarted and continued for 12 months. Arm A will restart oral antiplatelet drugs&#xD;
      by giving aspirin 100mg qd, Arm B will also restart oral antiplatelet drugs by giving&#xD;
      ticagrelor 90mg bid plus aspirin 100mg qd and Arm C will also restart oral antiplatelet drugs&#xD;
      by giving ticagrelor 90mg bid. Treatment will continue for 12 months, at which time patients&#xD;
      will undergo a multislice computed tomography angiography to assess vein graft patency.&#xD;
&#xD;
      This study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as&#xD;
      compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of&#xD;
      vein graft patency.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as&#xD;
      compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of&#xD;
      vein graft patency. The primary comparison includes two separate parts. One is to demonstrate&#xD;
      T+A better than A and the other is T better than A.&#xD;
&#xD;
      One year rate of vein graft patency in the aspirin group is estimated as 80%. The assumed&#xD;
      rate of ticagrelor plus aspirin is 90%. With a two-sided alpha level 0.05 and 80% power, 199&#xD;
      grafts to each group are required. On the other hand, if we assume the rate of ticagrelor&#xD;
      monotherapy has the 1-year vein graft patency rate of 87%, under the same two-sided 0.05&#xD;
      alpha 441 grafts in each arm will offer 80% power to show the superiority of ticagrelor along&#xD;
      for the primary efficacy end point.&#xD;
&#xD;
      Combined the above two assumptions, if the allocation rate is 1:1:1, this study needs to&#xD;
      recruit 1,323 grafts in total (441 in each) to achieve the pre-specified power for both the&#xD;
      two comparisons (T+A vs. A and T vs. A).&#xD;
&#xD;
      The principle investigator assumes that the average number of the vien grafts in one patient&#xD;
      is 2.7-3.0. With this assumption, 500 patients are to be recruited, which will provide us a&#xD;
      total of 1350 - 1500 grafts.&#xD;
&#xD;
      According to the above, this study will be a confirmatory clinical trial to the primary&#xD;
      endpoint.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Patency of Saphenous Vein Grafts</measure>
    <time_frame>up to 12 months</time_frame>
    <description>assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis &lt;50%) is defined as &quot;patency&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Patency of Saphenous Vein Grafts</measure>
    <time_frame>up to 7 days</time_frame>
    <description>assessed by MSCTA or CAG. FitzGibbon grade A (stenosis &lt;50%) is defined as &quot;patency&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Rate of Post-operative Atrial Fibrillation After CABG.</measure>
    <time_frame>up to 7 days</time_frame>
    <description>Number of Participants with Post-operative Atrial Fibrillation after CABG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Number of Participants Free of Angina per CCS Classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Major Adverse Cardiovascular Event (MACE)</measure>
    <time_frame>up to 12 months</time_frame>
    <description>MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of the Major Bleeding Events</measure>
    <time_frame>up to 12 months</time_frame>
    <description>According to modified TIMI criteria, the &quot;Major Bleeding Events&quot; is defined as the combination of CABG-related bleeding and non-CABG-related major bleeding(Intracranial bleeding, Clinically overt signs of hemorrhage with hemoglobin drop ≥5 g/dL and Fatal bleeding).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD)</measure>
    <time_frame>at 12 months</time_frame>
    <description>Not all but the patients recruited in Ruijin Hospital</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">500</enrollment>
  <condition>Coronary Artery Bypass</condition>
  <condition>Antiplatelet Agents</condition>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>aspirin 100mg tablet by mouth daily for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ticagrelor plus Aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ticagrelor 90mg tablet by mouth twice daily for 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_label>Ticagrelor plus Aspirin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor</intervention_name>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_label>Ticagrelor plus Aspirin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients able to provide written informed consent&#xD;
&#xD;
          -  Provision of informed consent prior to any study specific procedures&#xD;
&#xD;
          -  Female and male patients aged 18-80 years&#xD;
&#xD;
          -  Indication for CABG surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiogenic shock, haemodynamic instability&#xD;
&#xD;
          -  Need for urgent revascularization within 5 days from presentation&#xD;
&#xD;
          -  Single vessel disease&#xD;
&#xD;
          -  Two vessel disease with normal left ventricular function (&gt; 50%)&#xD;
&#xD;
          -  Need for concomitant other cardiac surgery (e.g. valve replacement)&#xD;
&#xD;
          -  Need for dual antiplatelet treatment for the patients undergoing CABG after acute&#xD;
             coronary syndrome(ACS)&#xD;
&#xD;
          -  Contraindication for aspirin and ticagrelor use(e.g. known allergy)&#xD;
&#xD;
          -  History of bleeding diathesis within 3 months prior presentation&#xD;
&#xD;
          -  History of significant GI bleed within 1 year prior presentation&#xD;
&#xD;
          -  History of peptic ulcer without GI bleeding in past 3 years&#xD;
&#xD;
          -  History of intracranial hemorrhage&#xD;
&#xD;
          -  History of moderate to severe liver impairment&#xD;
&#xD;
          -  Patient requires dialysis&#xD;
&#xD;
          -  Patient with an increased risk of bradycardic events (as patients without a pacemaker&#xD;
             who have sick sinus syndrome, 2nd or 3rd degree arteriolar-venular block or&#xD;
             bradycardic-related syncope)&#xD;
&#xD;
          -  Need vitamin K antagonist therapy after bypass surgery eg. persistent atrial&#xD;
             fibrillation, mechanical valves&#xD;
&#xD;
          -  Known, clinically important thrombocytopenia(i.e. &lt; 100*109/L)&#xD;
&#xD;
          -  Known, clinically important anaemia (i.e. &lt;100g/L)&#xD;
&#xD;
          -  Participation in another investigational drug or device study in the last 30 days&#xD;
&#xD;
          -  Pregnancy or lactation(for premenopausal women 2 methods of reliable contraception,&#xD;
             one of which must barrier method, are required)&#xD;
&#xD;
          -  Concomitant oral or intravenous therapy with strong cytochrome P450 3A4(CYP3A4)&#xD;
             inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4&#xD;
             inducers which cannot be stopped for the course of the study (strong inhibitors:&#xD;
             ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone,&#xD;
             ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, over 1 litre daily of&#xD;
             grapefruit juice. Substrates with narrow therapeutic index: cyclosporine, quinidine.&#xD;
             Strong inducers: rifampin, phenytoin, carbamazepine. )&#xD;
&#xD;
          -  Any other condition such as active cancer&#xD;
&#xD;
          -  Life expectancy less than 12 months that may result in protocol non-compliance or a&#xD;
             risk for being lost to follow up&#xD;
&#xD;
          -  Indication for major surgery(e.g. cancer treatment, carotid surgery, cerebral surgery,&#xD;
             major vascular surgery)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qiang Zhao, MD.PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yunpeng Zhu, MD.</last_name>
    <role>Study Director</role>
    <affiliation>Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Henan Provincial People's Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangsu Province Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nan Jing First Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruijin Hospital, Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xinhua Hospital, Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changhai Hospital of Shanghai</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <results_first_submitted>January 3, 2019</results_first_submitted>
  <results_first_submitted_qc>April 5, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 1, 2019</results_first_posted>
  <last_update_submitted>August 4, 2019</last_update_submitted>
  <last_update_submitted_qc>August 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Qiang Zhao,MD</investigator_full_name>
    <investigator_title>Vice President of Ruijin Hospital, Professor and director, Department of Cardiac Surgery</investigator_title>
  </responsible_party>
  <keyword>CABG</keyword>
  <keyword>Antiplatelet</keyword>
  <keyword>Ticagrelor</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT02201771/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 28, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT02201771/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Aspirin</title>
          <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
        </group>
        <group group_id="P2">
          <title>Ticagrelor Plus Aspirin</title>
          <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
        </group>
        <group group_id="P3">
          <title>Ticagrelor</title>
          <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="166"/>
                <participants group_id="P2" count="168"/>
                <participants group_id="P3" count="166"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="153"/>
                <participants group_id="P2" count="158"/>
                <participants group_id="P3" count="156"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Aspirin</title>
          <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
        </group>
        <group group_id="B2">
          <title>Ticagrelor Plus Aspirin</title>
          <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
        </group>
        <group group_id="B3">
          <title>Ticagrelor</title>
          <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
        </group>
        <group group_id="B4">
          <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="166"/>
            <count group_id="B2" value="168"/>
            <count group_id="B3" value="166"/>
            <count group_id="B4" value="500"/>
          </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="64.0" spread="8.1"/>
                    <measurement group_id="B2" value="63.5" spread="8.2"/>
                    <measurement group_id="B3" value="63.3" spread="8.3"/>
                    <measurement group_id="B4" value="63.6" spread="8.2"/>
                  </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="25"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="91"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="141"/>
                    <measurement group_id="B2" value="134"/>
                    <measurement group_id="B3" value="134"/>
                    <measurement group_id="B4" value="409"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="166"/>
                    <measurement group_id="B2" value="168"/>
                    <measurement group_id="B3" value="166"/>
                    <measurement group_id="B4" value="500"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Patency of Saphenous Vein Grafts</title>
        <description>assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis &lt;50%) is defined as &quot;patency&quot;.</description>
        <time_frame>up to 12 months</time_frame>
        <population>ITT analysis, Patients with missing data were considered to have occluded saphenous vein grafts.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Plus Aspirin</title>
            <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor</title>
            <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
          </group>
        </group_list>
        <measure>
          <title>The Patency of Saphenous Vein Grafts</title>
          <description>assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis &lt;50%) is defined as &quot;patency&quot;.</description>
          <population>ITT analysis, Patients with missing data were considered to have occluded saphenous vein grafts.</population>
          <units>percentage of patent SV grafts</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>saphenous vein grafts</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="166"/>
                <count group_id="O2" value="168"/>
                <count group_id="O3" value="166"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>saphenous vein grafts</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="485"/>
                <count group_id="O2" value="487"/>
                <count group_id="O3" value="488"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.5" lower_limit="70.8" upper_limit="82.1"/>
                    <measurement group_id="O2" value="88.7" lower_limit="84.6" upper_limit="92.8"/>
                    <measurement group_id="O3" value="82.8" lower_limit="78.0" upper_limit="87.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Patency of Saphenous Vein Grafts</title>
        <description>assessed by MSCTA or CAG. FitzGibbon grade A (stenosis &lt;50%) is defined as &quot;patency&quot;.</description>
        <time_frame>up to 7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Plus Aspirin</title>
            <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor</title>
            <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
          </group>
        </group_list>
        <measure>
          <title>The Patency of Saphenous Vein Grafts</title>
          <description>assessed by MSCTA or CAG. FitzGibbon grade A (stenosis &lt;50%) is defined as &quot;patency&quot;.</description>
          <units>percentage of patent SV grafts</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>saphenous vein grafts</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="166"/>
                <count group_id="O2" value="168"/>
                <count group_id="O3" value="166"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>saphenous vein grafts</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="485"/>
                <count group_id="O2" value="487"/>
                <count group_id="O3" value="488"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.1" lower_limit="87.4" upper_limit="94.8"/>
                    <measurement group_id="O2" value="94.9" lower_limit="92.2" upper_limit="97.6"/>
                    <measurement group_id="O3" value="94.3" lower_limit="91.8" upper_limit="96.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Rate of Post-operative Atrial Fibrillation After CABG.</title>
        <description>Number of Participants with Post-operative Atrial Fibrillation after CABG</description>
        <time_frame>up to 7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Plus Aspirin</title>
            <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor</title>
            <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
          </group>
        </group_list>
        <measure>
          <title>The Rate of Post-operative Atrial Fibrillation After CABG.</title>
          <description>Number of Participants with Post-operative Atrial Fibrillation after CABG</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="166"/>
                <count group_id="O2" value="168"/>
                <count group_id="O3" value="166"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification</title>
        <description>Number of Participants Free of Angina per CCS Classification</description>
        <time_frame>up to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Plus Aspirin</title>
            <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor</title>
            <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
          </group>
        </group_list>
        <measure>
          <title>The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification</title>
          <description>Number of Participants Free of Angina per CCS Classification</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="166"/>
                <count group_id="O2" value="168"/>
                <count group_id="O3" value="166"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="154"/>
                    <measurement group_id="O2" value="158"/>
                    <measurement group_id="O3" value="155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Major Adverse Cardiovascular Event (MACE)</title>
        <description>MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)</description>
        <time_frame>up to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Plus Aspirin</title>
            <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor</title>
            <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Major Adverse Cardiovascular Event (MACE)</title>
          <description>MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="166"/>
                <count group_id="O2" value="168"/>
                <count group_id="O3" value="166"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of the Major Bleeding Events</title>
        <description>According to modified TIMI criteria, the &quot;Major Bleeding Events&quot; is defined as the combination of CABG-related bleeding and non-CABG-related major bleeding(Intracranial bleeding, Clinically overt signs of hemorrhage with hemoglobin drop ≥5 g/dL and Fatal bleeding).</description>
        <time_frame>up to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Plus Aspirin</title>
            <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor</title>
            <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
          </group>
        </group_list>
        <measure>
          <title>Number of the Major Bleeding Events</title>
          <description>According to modified TIMI criteria, the &quot;Major Bleeding Events&quot; is defined as the combination of CABG-related bleeding and non-CABG-related major bleeding(Intracranial bleeding, Clinically overt signs of hemorrhage with hemoglobin drop ≥5 g/dL and Fatal bleeding).</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="166"/>
                <count group_id="O2" value="168"/>
                <count group_id="O3" value="166"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD)</title>
        <description>Not all but the patients recruited in Ruijin Hospital</description>
        <time_frame>at 12 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Aspirin</title>
          <description>aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin</description>
        </group>
        <group group_id="E2">
          <title>Ticagrelor Plus Aspirin</title>
          <description>ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months&#xD;
Aspirin&#xD;
Ticagrelor</description>
        </group>
        <group group_id="E3">
          <title>Ticagrelor</title>
          <description>ticagrelor 90mg tablet by mouth twice daily for 12 months&#xD;
Ticagrelor</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Nonfatal myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Nonfatal stroke</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Cardiovascular death</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="78" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="91" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="74" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <description>Hemoglobin &lt; 70g/L</description>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Perioperative myocardial injury</sub_title>
                <description>cTn &gt; 10*URL but not myocardial infarction</description>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Incision complication</sub_title>
                <description>poor healing of incision</description>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoproteinemia</sub_title>
                <description>serum albumin&lt;25g/L</description>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="18" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal disfunction</sub_title>
                <description>Serum creatinine&gt;200umol/L</description>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="166"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="168"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="166"/>
              </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>Dr. Yunpeng Zhu</name_or_title>
      <organization>Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China</organization>
      <phone>008613816819346</phone>
      <email>zypB1014@rjh.com.cn</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/NCT02201771
org study id: ISSBRIL0211
nct id: NCT02201771
lead sponsor: 
The study population will include all patients undergoing elective CABG. Consent and
      randomization will occur before surgery. Total 500 patients undergoing elective CABG will be
      randomly assigned into three groups with 1:1:1 ratio(167 patients per group) in this
      open-label study. All the enrolled patients will stop oral antiplatelet drugs according to
      local protocol before the surgery. Within the first 24 hours after surgery, study medication
      should be restarted and continued for 12 months. Arm A will restart oral antiplatelet drugs
      by giving aspirin 100mg qd, Arm B will also restart oral antiplatelet drugs by giving
      ticagrelor 90mg bid plus aspirin 100mg qd and Arm C will also restart oral antiplatelet drugs
      by giving ticagrelor 90mg bid. Treatment will continue for 12 months, at which time patients
      will undergo a multislice computed tomography angiography to assess vein graft patency.

      This study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as
      compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of
      vein graft patency.
The study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as
      compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of
      vein graft patency. The primary comparison includes two separate parts. One is to demonstrate
      T+A better than A and the other is T better than A.

      One year rate of vein graft patency in the aspirin group is estimated as 80%. The assumed
      rate of ticagrelor plus aspirin is 90%. With a two-sided alpha level 0.05 and 80% power, 199
      grafts to each group are required. On the other hand, if we assume the rate of ticagrelor
      monotherapy has the 1-year vein graft patency rate of 87%, under the same two-sided 0.05
      alpha 441 grafts in each arm will offer 80% power to show the superiority of ticagrelor along
      for the primary efficacy end point.

      Combined the above two assumptions, if the allocation rate is 1:1:1, this study needs to
      recruit 1,323 grafts in total (441 in each) to achieve the pre-specified power for both the
      two comparisons (T+A vs. A and T vs. A).

      The principle investigator assumes that the average number of the vien grafts in one patient
      is 2.7-3.0. With this assumption, 500 patients are to be recruited, which will provide us a
      total of 1350 - 1500 grafts.

      According to the above, this study will be a confirmatory clinical trial to the primary
      endpoint.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Patency of Saphenous Vein Grafts
time frame: up to 12 months
description: assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis <50%) is defined as "patency".
measure: The Patency of Saphenous Vein Grafts
time frame: up to 7 days
description: assessed by MSCTA or CAG. FitzGibbon grade A (stenosis <50%) is defined as "patency".
measure: The Rate of Post-operative Atrial Fibrillation After CABG.
time frame: up to 7 days
description: Number of Participants with Post-operative Atrial Fibrillation after CABG
measure: The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification
time frame: up to 12 months
description: Number of Participants Free of Angina per CCS Classification
measure: The Number of Major Adverse Cardiovascular Event (MACE)
time frame: up to 12 months
description: MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)
measure: Number of the Major Bleeding Events
time frame: up to 12 months
description: According to modified TIMI criteria, the "Major Bleeding Events" is defined as the combination of CABG-related bleeding and non-CABG-related major bleeding(Intracranial bleeding, Clinically overt signs of hemorrhage with hemoglobin drop ≥5 g/dL and Fatal bleeding).
measure: The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD)
time frame: at 12 months
description: Not all but the patients recruited in Ruijin Hospital
arm group label: Aspirin
arm group type: Active Comparator
description: aspirin 100mg tablet by mouth daily for 12 months
arm group label: Ticagrelor plus Aspirin
arm group type: Experimental
description: ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months
arm group label: Ticagrelor
arm group type: Experimental
description: ticagrelor 90mg tablet by mouth twice daily for 12 months
intervention type: Drug
intervention name: Aspirin
arm group label: Aspirin
arm group label: Ticagrelor plus Aspirin
intervention type: Drug
intervention name: Ticagrelor
arm group label: Ticagrelor
arm group label: Ticagrelor plus Aspirin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Qiang Zhao, MD.PhD
role: Principal Investigator
affiliation: Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China
last name: Yunpeng Zhu, MD.
role: Study Director
affiliation: Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Qiang Zhao,MD
investigator title: Vice President of Ruijin Hospital, Professor and director, Department of Cardiac Surgery
mesh term: Aspirin
mesh term: Ticagrelor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 