<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/NCT02222818</url>
  </required_header>
  <id_info>
    <org_study_id>CRTee</org_study_id>
    <nct_id>NCT02222818</nct_id>
  </id_info>
  <brief_title>Cardiac Resynchronization Therapy Efficacy Enhancements</brief_title>
  <acronym>CRTee</acronym>
  <official_title>Cardiac Resynchronization Therapy Efficacy Enhancements</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medtronic Cardiac Rhythm and Heart Failure</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medtronic Cardiac Rhythm and Heart Failure</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate that the amount of effective CRT (Cardiac&#xD;
      Resynchronization Therapy) pacing during AF (atrial fibrillation) when CAFRPlus (Conducted AF&#xD;
      Response Plus) is applied is not inferior to the amount of effective CRT pacing during AF&#xD;
      when CAFR (Conducted AF Response) is applied.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The CRTee study is an IDE, prospective, multi-center, randomized, controlled, crossover&#xD;
      clinical study, conducted worldwide and designed to demonstrate that the amount of effective&#xD;
      CRT pacing during AF (atrial fibrillation) when CAFRPlus (Conducted AF Response Plus) is&#xD;
      applied is not inferior to the amount of effective CRT pacing during AF when CAFR (Conducted&#xD;
      AF Response) is applied.&#xD;
&#xD;
      The study will be conducted at up to 30 centers located in the United States, Europe and&#xD;
      Middle East and Africa (MEA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Effective CRT Pacing During AF (Non-inferiority Test)</measure>
    <time_frame>Up to 4 months</time_frame>
    <description>The primary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is not inferior to when CAFR is applied (non-inferiority test).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Effective CRT Pacing During AF (Superiority Test)</measure>
    <time_frame>Up to 4 months</time_frame>
    <description>The secondary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is greater than when CAFR is applied (superiority test).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Group A: CAFR first</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects randomized to Group A will receive CAFR first, then cross over to CAFRPlus.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: CAFRPlus first</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects randomized to Group B will receive CAFRPlus first, then cross over to CAFR.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Conducted AF Response (CAFR)</intervention_name>
    <description>The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.</description>
    <arm_group_label>Group A: CAFR first</arm_group_label>
    <arm_group_label>Group B: CAFRPlus first</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Conducted AF Response Plus (CAFRPlus)</intervention_name>
    <description>The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.</description>
    <arm_group_label>Group A: CAFR first</arm_group_label>
    <arm_group_label>Group B: CAFRPlus first</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is willing to sign and date the study patient Informed Consent form.&#xD;
&#xD;
          -  Subject is at least 18 years of age (or older, if required by local law).&#xD;
&#xD;
          -  Subject is expected to remain available after enrollment to complete follow-up visits&#xD;
             in both arms of the study&#xD;
&#xD;
          -  Subject has had a Medtronic Viva or Brava CRT-D device implanted at least 30 days&#xD;
             prior to enrollment.&#xD;
&#xD;
          -  Subject has history of AF burden, of at least 6 days of at least 4 hours of AF over&#xD;
             any 4 week period within the last 90 days as documented in device diagnostic data OR&#xD;
             if subject has no atrial lead (therefore no device diagnostic data) but clinical&#xD;
             evidence of high AF burden.&#xD;
&#xD;
          -  Subject has demonstrated history of being able to complete Left Ventricular Capture&#xD;
             Management (LVCM) documented in device data.&#xD;
&#xD;
          -  Subject has a documented % V pacing during AF of less than or equal to 97% within 90&#xD;
             days prior to enrollment or within 10 days after enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has undergone AV node ablation for treatment of AF.&#xD;
&#xD;
          -  Subject has complete or 3rd degree AV block.&#xD;
&#xD;
          -  Subject has had an MI within 30 days.&#xD;
&#xD;
          -  Subject has medical conditions that limit study participation (per physician&#xD;
             discretion).&#xD;
&#xD;
          -  Subject is enrolled in one or more concurrent studies that could confound the study&#xD;
             results as determined by Medtronic.&#xD;
&#xD;
          -  Subject has a limited life expectancy for non-cardiac causes that would not allow&#xD;
             completion of the study.&#xD;
&#xD;
          -  Subject is pregnant (in the US, all women of child-bearing potential must undergo a&#xD;
             pregnancy test within seven days prior to CRTee download).&#xD;
&#xD;
          -  Subject meets the exclusion criteria required by local law.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Suneet Mittal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Valley Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cardiac Arrythmia Services</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Heart Center</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Memorial Heart and Vascular</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CentraCare</name>
      <address>
        <city>St. Cloud</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Carolina Heart and Vascular</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Carmel</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oklahoma Heart</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Berks Cardiology</name>
      <address>
        <city>Reading</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Cardiac Arrhythmia Services</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kootenai Heart Clinics</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magyar Honvédség Honvédkorház</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Agostino Gemelli</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Bolognini Seriate - Ospedale Bolognini</name>
      <address>
        <city>Seriate</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Cardinale Panico</name>
      <address>
        <city>Tricase</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince Sultan Cardiac Center</name>
      <address>
        <city>Riyadh</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vychodoslovensky ustav srdcovych a cievnych chorob, a.s.</name>
      <address>
        <city>Kosice</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mediclinic Panorama</name>
      <address>
        <city>Cape Town</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Heart and Chest Hospital NHS Foundation Trust</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>he Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Saudi Arabia</country>
    <country>Slovakia</country>
    <country>South Africa</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>November 8, 2016</results_first_submitted>
  <results_first_submitted_qc>November 8, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 6, 2017</results_first_posted>
  <last_update_submitted>November 8, 2016</last_update_submitted>
  <last_update_submitted_qc>November 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 71 subjects were enrolled from 22 investigational centers in the United States, Europe and Middle East. The first subject was enrolled on 07 Oct 2014, and last enrollment was on 08 Jan 2016.</recruitment_details>
      <pre_assignment_details>Of the 71 enrolled subjects, 5 did not meet eligibility criteria (AV node ablation - 2, complete heart block - 3) and were exited from the study prior to randomization assignment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Group A: CAFR First</title>
          <description>Subjects randomized to Group A will receive CAFR first, then cross over to CAFRPlus.&#xD;
Conducted AF Response (CAFR): The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.&#xD;
Conducted AF Response Plus (CAFRPlus): The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.</description>
        </group>
        <group group_id="P2">
          <title>Group B: CAFRPlus First</title>
          <description>Subjects randomized to Group B will receive CAFRPlus first, then cross over to CAFR.&#xD;
Conducted AF Response (CAFR): The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.&#xD;
Conducted AF Response Plus (CAFRPlus): The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33">Start of CAFR evaluation period</participants>
                <participants group_id="P2" count="33">Start of CAFRPlus evaluation period</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33">End of CAFR evaluation period</participants>
                <participants group_id="P2" count="30">End of CAFRPlus evaluation period</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Eligibility criteria not met</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33">Start of CAFRPlus evaluation period</participants>
                <participants group_id="P2" count="30">Start of CAFR evaluation period</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33">End of CAFRPlus evaluation period</participants>
                <participants group_id="P2" count="30">End of CAFR evaluation period</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All subjects randomized to either Group A (CAFR first) or Group B (CAFRPlus first).</population>
      <group_list>
        <group group_id="B1">
          <title>Group A: CAFR First</title>
          <description>Subjects randomized to Group A will receive CAFR first, then cross over to CAFRPlus.&#xD;
Conducted AF Response (CAFR): The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.&#xD;
Conducted AF Response Plus (CAFRPlus): The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.</description>
        </group>
        <group group_id="B2">
          <title>Group B: CAFRPlus First</title>
          <description>Subjects randomized to Group B will receive CAFRPlus first, then cross over to CAFR.&#xD;
Conducted AF Response (CAFR): The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.&#xD;
Conducted AF Response Plus (CAFRPlus): The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.</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="33"/>
            <count group_id="B2" value="33"/>
            <count group_id="B3" value="66"/>
          </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="70.7" spread="11.6"/>
                    <measurement group_id="B2" value="72.4" spread="9.1"/>
                    <measurement group_id="B3" value="71.6" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="61"/>
                  </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>Saudi Arabia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hungary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Slovakia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <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>Percentage of Effective CRT Pacing During AF (Non-inferiority Test)</title>
        <description>The primary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is not inferior to when CAFR is applied (non-inferiority test).</description>
        <time_frame>Up to 4 months</time_frame>
        <population>Randomized subjects who had paired measurements available from both CAFR period and CAFRPlus period.</population>
        <group_list>
          <group group_id="O1">
            <title>CAFR ON</title>
            <description>Percentage of effective CRT pacing during AF when CAFR is ON</description>
          </group>
          <group group_id="O2">
            <title>CAFRPlus ON</title>
            <description>Percentage of effective CRT pacing during AF when CAFRPlus is ON</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Effective CRT Pacing During AF (Non-inferiority Test)</title>
          <description>The primary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is not inferior to when CAFR is applied (non-inferiority test).</description>
          <population>Randomized subjects who had paired measurements available from both CAFR period and CAFRPlus period.</population>
          <units>percentage of effective CRT pacing</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.8" spread="14.3"/>
                    <measurement group_id="O2" value="87.8" spread="7.8"/>
                  </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>
            <groups_desc>Null Hypothesis (Ho): μd ≤ -2% Alternative Hypothesis (Ha): μd &gt; -2% where μd is the paired difference in percent effective CRT pacing during AF between when CAFRPlus is applied and when CAFR is applied, based on subjects' paired measurements from the two cross-over follow-up periods, and -2% is the non-inferiority margin selected based upon clinical judgment.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>In order to demonstrate that CAFRPlus is no less effective than CAFR by a non-inferiority margin of 2%, assuming a true paired difference of 6% and a standard deviation of 15% for the paired differences, a sample size of 39 subjects with paired data is required to achieve 90% statistical power using the one-sample t-test for non-inferiority, while controlling the one-sided type I error rate at 0.025.</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The threshold for statistical significance was 0.0207, determined by the pre-specified alpha spending function accounting for one interim analysis.</p_value_desc>
            <method>t-test, 1 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>7.0</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>8.7</dispersion_value>
            <ci_percent>95.86</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.5</ci_lower_limit>
            <ci_upper_limit>9.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Effective CRT Pacing During AF (Superiority Test)</title>
        <description>The secondary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is greater than when CAFR is applied (superiority test).</description>
        <time_frame>Up to 4 months</time_frame>
        <population>Randomized subjects who had paired measurements available from both CAFR period and CAFRPlus period.</population>
        <group_list>
          <group group_id="O1">
            <title>CAFR ON</title>
            <description>Percentage of effective CRT pacing during AF when CAFR is ON</description>
          </group>
          <group group_id="O2">
            <title>CAFRPlus ON</title>
            <description>Percentage of effective CRT pacing during AF when CAFRPlus is ON</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Effective CRT Pacing During AF (Superiority Test)</title>
          <description>The secondary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is greater than when CAFR is applied (superiority test).</description>
          <population>Randomized subjects who had paired measurements available from both CAFR period and CAFRPlus period.</population>
          <units>percentage of effective CRT pacing</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.8" spread="14.3"/>
                    <measurement group_id="O2" value="87.8" spread="7.8"/>
                  </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>
            <groups_desc>Null Hypothesis (Ho): μd ≤ 0% Alternative Hypothesis (Ha): μd &gt; 0% where μd is the paired difference in percent effective CRT pacing during AF between when CAFRPlus is applied and when CAFR is applied, based on subjects' paired measurements from the two cross-over follow-up periods.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The threshold for statistical significance was 0.0207, determined by the pre-specified alpha spending function accounting for one interim analysis.</p_value_desc>
            <method>t-test, 1 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>7.0</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>8.7</dispersion_value>
            <ci_percent>95.86</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.5</ci_lower_limit>
            <ci_upper_limit>9.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected throughout entire study follow-up (from enrollment to study exit). Subjects' follow-up duration ranged from 0 to 5.4 months, with an average of 2.7 ± 1.6 months for all enrolled subjects.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>All Enrolled Subjects</title>
          <description>All subjects enrolled in the CRTee study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Non-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="7" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Ventricular arrhythmia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <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="5" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="71"/>
              </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>Generally, contracts allow investigators to publish study results per the protocol and publication plan. Investigators and Participating Institutions will provide any publication of Study Data generated by PI and/or Participating Institution to Medtronic for review prior to submission to determine if confidential information (&quot;CI&quot;) is included and to check for technical correctness. Medtronic may not censor/interfere with the publication beyond the extent necessary to protect CI.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>CRTee Clinical Team</name_or_title>
      <organization>Medtronic Cardiac Rhythm and Heart Failure</organization>
      <phone>800-328-2518</phone>
      <email>MedtronicCRMtrials@medtronic.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/NCT02222818
org study id: CRTee
nct id: NCT02222818
lead sponsor: 
has dmc: No
The purpose of this study is to demonstrate that the amount of effective CRT (Cardiac
      Resynchronization Therapy) pacing during AF (atrial fibrillation) when CAFRPlus (Conducted AF
      Response Plus) is applied is not inferior to the amount of effective CRT pacing during AF
      when CAFR (Conducted AF Response) is applied.
The CRTee study is an IDE, prospective, multi-center, randomized, controlled, crossover
      clinical study, conducted worldwide and designed to demonstrate that the amount of effective
      CRT pacing during AF (atrial fibrillation) when CAFRPlus (Conducted AF Response Plus) is
      applied is not inferior to the amount of effective CRT pacing during AF when CAFR (Conducted
      AF Response) is applied.

      The study will be conducted at up to 30 centers located in the United States, Europe and
      Middle East and Africa (MEA).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Effective CRT Pacing During AF (Non-inferiority Test)
time frame: Up to 4 months
description: The primary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is not inferior to when CAFR is applied (non-inferiority test).
measure: Percentage of Effective CRT Pacing During AF (Superiority Test)
time frame: Up to 4 months
description: The secondary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is greater than when CAFR is applied (superiority test).
arm group label: Group A: CAFR first
arm group type: Other
description: Subjects randomized to Group A will receive CAFR first, then cross over to CAFRPlus.
arm group label: Group B: CAFRPlus first
arm group type: Other
description: Subjects randomized to Group B will receive CAFRPlus first, then cross over to CAFR.
intervention type: Device
intervention name: Conducted AF Response (CAFR)
description: The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.
arm group label: Group A: CAFR first
arm group label: Group B: CAFRPlus first
intervention type: Device
intervention name: Conducted AF Response Plus (CAFRPlus)
description: The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.
arm group label: Group A: CAFR first
arm group label: Group B: CAFRPlus first
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Suneet Mittal, MD
role: Principal Investigator
affiliation: Valley Health System
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country: Hungary
country: Italy
country: Saudi Arabia
country: Slovakia
country: South Africa
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Atrial Fibrillation
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 