<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/NCT03839355</url>
  </required_header>
  <id_info>
    <org_study_id>17-010544</org_study_id>
    <nct_id>NCT03839355</nct_id>
  </id_info>
  <brief_title>Trial of Apixaban vs Warfarin in Reducing Rate of Cognitive Decline, Silent Cerebral Infarcts and Cerebral Microbleeds in Patients With Atrial Fibrillation</brief_title>
  <acronym>ARISTA</acronym>
  <official_title>Randomized Trial of Apixaban vs Dose Adjusted Warfarin in Reducing Rate of Cognitive Function Decline, Silent Cerebral Infarcts and Cerebral Microbleeds in Non-valvular Atrial Fibrillation Patients With CHA2DS2-VaSc Score = 2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators' central hypothesis is that in patients with atrial fibrillation,&#xD;
      anticoagulation with Apixaban reduces the rate of decline in cognitive function, when&#xD;
      compared to Warfarin. The investigators also hypothesize that Apixaban reduces cognitive&#xD;
      decline by reducing the rate of new cerebral infarction and cerebral microbleeds detected by&#xD;
      cerebral MRI compared to warfarin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to slower than anticipated enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">December 19, 2018</start_date>
  <completion_date type="Actual">December 15, 2020</completion_date>
  <primary_completion_date type="Actual">December 15, 2020</primary_completion_date>
  <phase>Phase 3</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>Other</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Standardized Neurocognitive Function Score</measure>
    <time_frame>Baseline, Year 1, Year 2</time_frame>
    <description>Assess the change in cognitive function using standardized neurocognitive assessment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MRI Evidence of Silent Cerebral Infarct</measure>
    <time_frame>Baseline, Year 2</time_frame>
    <description>Magnetic Resonance Imagining of the brain to assess the development of new silent cerebral infarcts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MRI Evidence of New Cerebral Micro-bleeds</measure>
    <time_frame>Baseline, Year 2</time_frame>
    <description>Magnetic Resonance Imagining of the brain to assess the development of new cerebral micro-bleeds</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Eliquis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban</intervention_name>
    <description>Dosage either 5mg or 2.5mg for 2 years</description>
    <arm_group_label>Eliquis</arm_group_label>
    <other_name>Eliquis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <description>Dosage assessed by your treating physician for 2 years</description>
    <arm_group_label>Warfarin</arm_group_label>
    <other_name>Coumadin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-valvular Atrial Fibrillation&#xD;
&#xD;
          -  CHA2DS2-VASc Score &gt; or = to 2&#xD;
&#xD;
          -  Never been treated with Apixaban (Eliquis) or prior treatment of &lt; 1 month&#xD;
&#xD;
          -  Candidate for oral anticoagulation as assessed by a treating physician&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Valvular Atrial Fibrillation (Rheumatic valve disease,Moderate or greater mitral&#xD;
             stenosis,Mechanical cardiac valve)&#xD;
&#xD;
          -  Active Bleeding&#xD;
&#xD;
          -  Prior treatment with Apixaban &gt;1 month&#xD;
&#xD;
          -  Recent stroke within 7 days&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Implanted devices not compatible with MRI/any cardiac implanted device&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Active alcohol/drug abuse&#xD;
&#xD;
          -  Life expectancy &lt; 1 year&#xD;
&#xD;
          -  Taking asprin with &gt;100mg doses&#xD;
&#xD;
          -  Known hypersensitivity to warfarin or Apixaban&#xD;
&#xD;
          -  Severe renal insufficiency&#xD;
&#xD;
          -  Prior severe bleeding (Intracranial bleeding (subdural, subarachnoid, intraparenchymal&#xD;
             bleeding),GI bleed requiring transfusion,Bleeding from other sites requiring&#xD;
             transfusion)&#xD;
&#xD;
          -  Psychosocial reasons that make study participation impractical&#xD;
&#xD;
          -  Currently enrolled in another IND or IDE trial that has not completed the primary&#xD;
             endpoint or that clinically interferes with the current study endpoints&#xD;
&#xD;
          -  Co-morbid condition(s) that could limit the subject's ability to participate in the&#xD;
             trial or to comply with follow-up requirements, or that could impact the scientific&#xD;
             integrity of the study.&#xD;
&#xD;
          -  Prisoners or subjects who are involuntarily incarcerated&#xD;
&#xD;
          -  Subjects who are compulsorily detained for treatment of either psychiatric or physical&#xD;
             illness&#xD;
&#xD;
          -  Current or expected systemic treatment with strong dual inhibitors of CYP3A4 and P-gp&#xD;
             (Any one of rifampin, carbamazepine, phenytoin, St. John's Wort, ketoconazole,&#xD;
             itraconazole, ritonavir, clarithromycin)&#xD;
&#xD;
          -  Need for dual anti-platelet therapy with aspirin and another agent such as&#xD;
             thienopyridine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Malini Madhavan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 13, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <results_first_submitted>February 5, 2021</results_first_submitted>
  <results_first_submitted_qc>February 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 16, 2021</results_first_posted>
  <last_update_submitted>February 23, 2021</last_update_submitted>
  <last_update_submitted_qc>February 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Malini Madhavan</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Apixaban</keyword>
  <keyword>Warfarin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Apixaban</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03839355/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Eliquis</title>
          <description>Apixaban: Dosage either 5mg or 2.5mg for 2 years</description>
        </group>
        <group group_id="P2">
          <title>Warfarin</title>
          <description>Warfarin: Dosage assessed by your treating physician for 2 years</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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>
      <group_list>
        <group group_id="B1">
          <title>Eliquis</title>
          <description>Apixaban: Dosage either 5mg or 2.5mg for 2 years</description>
        </group>
        <group group_id="B2">
          <title>Warfarin</title>
          <description>Warfarin: Dosage assessed by your treating physician for 2 years</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="18"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77.4" spread="5.84"/>
                    <measurement group_id="B2" value="76.4" spread="5.61"/>
                    <measurement group_id="B3" value="76.9" spread="5.72"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </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>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Standardized Neurocognitive Function Score</title>
        <description>Assess the change in cognitive function using standardized neurocognitive assessment.</description>
        <time_frame>Baseline, Year 1, Year 2</time_frame>
        <population>Study terminated due to slower than anticipated enrollment. Data was not collected or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Eliquis</title>
            <description>Apixaban: Dosage either 5mg or 2.5mg for 2 years</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Warfarin: Dosage assessed by your treating physician for 2 years</description>
          </group>
        </group_list>
        <measure>
          <title>Standardized Neurocognitive Function Score</title>
          <description>Assess the change in cognitive function using standardized neurocognitive assessment.</description>
          <population>Study terminated due to slower than anticipated enrollment. Data was not collected or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>MRI Evidence of Silent Cerebral Infarct</title>
        <description>Magnetic Resonance Imagining of the brain to assess the development of new silent cerebral infarcts.</description>
        <time_frame>Baseline, Year 2</time_frame>
        <population>Study terminated due to slower than anticipated enrollment. Data was not collected or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Eliquis</title>
            <description>Apixaban: Dosage either 5mg or 2.5mg for 2 years</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Warfarin: Dosage assessed by your treating physician for 2 years</description>
          </group>
        </group_list>
        <measure>
          <title>MRI Evidence of Silent Cerebral Infarct</title>
          <description>Magnetic Resonance Imagining of the brain to assess the development of new silent cerebral infarcts.</description>
          <population>Study terminated due to slower than anticipated enrollment. Data was not collected or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>MRI Evidence of New Cerebral Micro-bleeds</title>
        <description>Magnetic Resonance Imagining of the brain to assess the development of new cerebral micro-bleeds</description>
        <time_frame>Baseline, Year 2</time_frame>
        <population>Study terminated due to slower than anticipated enrollment. Data was not collected or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Eliquis</title>
            <description>Apixaban: Dosage either 5mg or 2.5mg for 2 years</description>
          </group>
          <group group_id="O2">
            <title>Warfarin</title>
            <description>Warfarin: Dosage assessed by your treating physician for 2 years</description>
          </group>
        </group_list>
        <measure>
          <title>MRI Evidence of New Cerebral Micro-bleeds</title>
          <description>Magnetic Resonance Imagining of the brain to assess the development of new cerebral micro-bleeds</description>
          <population>Study terminated due to slower than anticipated enrollment. Data was not collected or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from baseline to end of treatment for approximately 24 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Eliquis</title>
          <description>Apixaban: Dosage either 5mg or 2.5mg for 2 years</description>
        </group>
        <group group_id="E2">
          <title>Warfarin</title>
          <description>Warfarin: Dosage assessed by your treating physician for 2 years</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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. Malini Madhavan</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-255-4152</phone>
      <email>Madhavan.Malini@mayo.edu</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/NCT03839355
org study id: 17-010544
nct id: NCT03839355
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The investigators' central hypothesis is that in patients with atrial fibrillation,
      anticoagulation with Apixaban reduces the rate of decline in cognitive function, when
      compared to Warfarin. The investigators also hypothesize that Apixaban reduces cognitive
      decline by reducing the rate of new cerebral infarction and cerebral microbleeds detected by
      cerebral MRI compared to warfarin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Outcomes Assessor)
measure: Standardized Neurocognitive Function Score
time frame: Baseline, Year 1, Year 2
description: Assess the change in cognitive function using standardized neurocognitive assessment.
measure: MRI Evidence of Silent Cerebral Infarct
time frame: Baseline, Year 2
description: Magnetic Resonance Imagining of the brain to assess the development of new silent cerebral infarcts.
measure: MRI Evidence of New Cerebral Micro-bleeds
time frame: Baseline, Year 2
description: Magnetic Resonance Imagining of the brain to assess the development of new cerebral micro-bleeds
arm group label: Eliquis
arm group type: Active Comparator
arm group label: Warfarin
arm group type: Active Comparator
intervention type: Drug
intervention name: Apixaban
description: Dosage either 5mg or 2.5mg for 2 years
arm group label: Eliquis
other name: Eliquis
intervention type: Drug
intervention name: Warfarin
description: Dosage assessed by your treating physician for 2 years
arm group label: Warfarin
other name: Coumadin
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Malini Madhavan
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Malini Madhavan
investigator title: Principal Investigator
mesh term: Cerebral Infarction
mesh term: Atrial Fibrillation
mesh term: Warfarin
mesh term: Apixaban
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 