<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/NCT03752151</url>
  </required_header>
  <id_info>
    <org_study_id>MDT18024</org_study_id>
    <nct_id>NCT03752151</nct_id>
  </id_info>
  <brief_title>Micra Atrial TRacking Using A Ventricular AccELerometer 2</brief_title>
  <acronym>MARVEL2</acronym>
  <official_title>Micra Atrial TRacking Using A Ventricular AccELerometer 2</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the Micra Atrial TRacking Using A Ventricular AccELerometer 2 (MARVEL 2) study&#xD;
      is to demonstrate safe and effective operation of the MARVEL 2 features for providing AV&#xD;
      synchronous pacing in patients with normal sinus node function and AV block&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The MARVEL 2 study is an acute, prospective, global, multi-center, software-download clinical&#xD;
      study. The study is planned to be conducted in US, Europe, and Asia. The study is expected to&#xD;
      be conducted at approximately 15-20 centers in up to 100 subjects to obtain at least 70&#xD;
      usable Holter datasets to meet the objectives of the study. The expected total study duration&#xD;
      (from first subject enrollment to the exit of the last subject) is approximately 6-months;&#xD;
      this represents the time necessary to enroll the target sample size of at least 70 subjects&#xD;
      with usable Holter datasets. Software will be downloaded into patients implanted with a Micra&#xD;
      device to allow the new algorithm performance to be measured in patients where a Micra device&#xD;
      has already been chosen as most appropriate for the patient.&#xD;
&#xD;
      Most enrolled subjects will complete the study procedures during a single study visit.&#xD;
      However, subjects enrolling in the study at the time of their Micra implant (anticipated to&#xD;
      be approximately 10 subjects) will have the investigational algorithm downloaded following&#xD;
      Micra implant, prior to hospital discharge, and approximately 1-month post-implant. This&#xD;
      subset of subjects with de novo Micra implants will allow the MARVEL 2 features to be tested&#xD;
      at multiple points in the device life cycle.&#xD;
&#xD;
      Since the download algorithm running in a Micra device significantly increases current drain,&#xD;
      a 2-4 hour acute study is used to limit the reduction in device longevity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2019</start_date>
  <completion_date type="Actual">August 7, 2019</completion_date>
  <primary_completion_date type="Actual">August 7, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Subjects enrolled in the MARVEL 2 study. Enrolled subjects will have the MARVEL 2 algorithm downloaded into their implanted market released Micra device. Each subject will be tested during when the MARVEL 2 algorithm is in monitor mode (VVI pacing) and in adaptive mode (VDD pacing).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Echocardiogram core lab will be masked to the individual patient subjects and MARVEL 2 algorithm mode.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Atrial Ventricular Pacing Synchrony Success During Rest</measure>
    <time_frame>40 Minutes</time_frame>
    <description>A subject will meet the primary endpoint if a paced or sensed ventricular beat is within 300 ms following an ECG confirmed P-wave for at least 70% of the ECG confirmed P-waves. The primary endpoint will be evaluated during the MARVEL 2 setup phase during MARVEL 2 Algorithm monitor mode (VDI pacing which is effectively VVI pacing) and during the 20-minute resting period in which the MARVEL 2 Algorithm is programmed to Adaptive mode (VDD pacing)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Free From Inappropriate Pacemaker Function Events</measure>
    <time_frame>Through study completion an average of one day</time_frame>
    <description>A participant will meet the primary endpoint if they are free from the following MARVEL 2 software related events during the entire Holter monitoring period where the MARVEL 2 features are enabled.&#xD;
Inappropriate pacemaker function events are defined as:&#xD;
Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR&#xD;
Pacemaker oversensing induced tachycardia exceeding 3-minutes, defined as oversensing of the pacemaker's accelerometer signal leading to a heart rate exceeding 100 beats per minute.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left Ventricular Outflow Tract Velocity Time Integral</measure>
    <time_frame>12 cardiac cycles</time_frame>
    <description>The secondary endpoint is left ventricular outflow tract (LVOT) velocity time integral (VTI) as obtained from echocardiogram while the MARVEL 2 features are in adaptive mode (VDD pacing) and while the MARVEL 2 features are in monitor mode (VDI pacing which is effectively VVI pacing). This was measured by the echo core laboratory that was blinded to the study participant and MARVEL 2 algorithm mode.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">77</enrollment>
  <condition>Atrioventricular Conduction Block</condition>
  <arm_group>
    <arm_group_label>MARVEL 2 Algorithm Monitor Mode, Then MARVEL 2 Adaptive Mode</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first received MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes followed by MARVEL 2 algorithm adaptive mode for approximately 2 hours which provides VDD pacing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MARVEL 2 Algorithm Monitor Mode then Adaptive Mode</intervention_name>
    <description>Software download into implanted Micra device and programmed to MARVEL 2 Monitor Mode then MARVEL 2 Adaptive Mode</description>
    <arm_group_label>MARVEL 2 Algorithm Monitor Mode, Then MARVEL 2 Adaptive Mode</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject has been implanted with a Micra TPS (Model MC1VR01) with remaining device&#xD;
             longevity of 6 years or more or is expected to be implanted with a Micra TPS.&#xD;
&#xD;
          -  Subject has history of AV block*&#xD;
&#xD;
          -  Subject is ≥ 18 years old and as per required local law.&#xD;
&#xD;
          -  Subject (and/or witness as applicable per local regulations) provides signed and dated&#xD;
             authorization and/or consent per institution and local requirements.&#xD;
&#xD;
          -  Subject is willing and able to comply with the protocol. *This includes subjects with&#xD;
             normal sinus function and persistent 3rd degree AV block and subjects with other forms&#xD;
             of AV block.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject is currently enrolled or planning to participate in a potentially confounding&#xD;
             drug or device trial during the study. Co-enrollment in concurrent trials is only&#xD;
             allowed when documented pre-approval is obtained from the Medtronic Clinical Research&#xD;
             Specialist.&#xD;
&#xD;
          -  Subject is pregnant (if required by local law, women of child-bearing potential must&#xD;
             undergo a pregnancy test within seven days prior to MARVEL 2 study procedures).&#xD;
&#xD;
          -  Subject meets any exclusion criteria required by local law (age or other).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Baptist Medical Center Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital- Northwell</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kepler Universitätsklinikum Med Campus III</name>
      <address>
        <city>Linz</city>
        <zip>4020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven - Campus Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense Universitetshospital</name>
      <address>
        <city>Odense C</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Haut-Lévêque - CHU de Bordeaux</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Jantung Negara</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50400</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Hong Kong</country>
    <country>Malaysia</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czechia</country>
    <country>Italy</country>
  </removed_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <results_first_submitted>May 14, 2020</results_first_submitted>
  <results_first_submitted_qc>May 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 4, 2020</results_first_posted>
  <last_update_submitted>May 29, 2020</last_update_submitted>
  <last_update_submitted_qc>May 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</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>Heart Block</mesh_term>
    <mesh_term>Atrioventricular Block</mesh_term>
  </condition_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>November 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03752151/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>March 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03752151/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were considered enrolled when they signed informed consent Subjects were enrolled between 22 January 2019 and 14 June 2019 at 12 study centers in 8 countries</recruitment_details>
      <pre_assignment_details>Following enrollment, the MARVEL 2 algorithm was downloaded into the subject's implanted Micra pacemaker. Following download subjects were programmed to MARVEL 2 Algorithm monitor mode followed by MARVEL 2 adaptive mode. Two subjects exited prior to MARVEL 2 download; one did not meet the study inclusion/exclusion and one withdrew consent.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive Mode</title>
          <description>Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline population is the number of participants who signed the study's informed consent</population>
      <group_list>
        <group group_id="B1">
          <title>MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive</title>
          <description>Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="77"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>One patient who withdrew prior to download of the MARVEL 2 algorithm did not complete the baseline procedures.</population>
          <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="76"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77.6" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>One patient who withdrew prior to download of the MARVEL 2 algorithm did not complete the baseline procedures.</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="76"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                  </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_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Austria</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hong Kong</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Malaysia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Predominant heart rhythm</title>
          <description>Predominant heart rhythm as assessed on electrocardiogram during Holter monitoring</description>
          <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="77"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Persistent 3rd degree AV block with normal sinus</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Intact atrioventricular conduction</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other rhythm</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rhythm indeterminate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Participant exited prior to software download</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Atrial Ventricular Pacing Synchrony Success During Rest</title>
        <description>A subject will meet the primary endpoint if a paced or sensed ventricular beat is within 300 ms following an ECG confirmed P-wave for at least 70% of the ECG confirmed P-waves. The primary endpoint will be evaluated during the MARVEL 2 setup phase during MARVEL 2 Algorithm monitor mode (VDI pacing which is effectively VVI pacing) and during the 20-minute resting period in which the MARVEL 2 Algorithm is programmed to Adaptive mode (VDD pacing)</description>
        <time_frame>40 Minutes</time_frame>
        <population>Participants with a predominant heart rhythm of 3rd degree atrioventricular block and normal sinus function during the study period.</population>
        <group_list>
          <group group_id="O1">
            <title>MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive</title>
            <description>Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Atrial Ventricular Pacing Synchrony Success During Rest</title>
          <description>A subject will meet the primary endpoint if a paced or sensed ventricular beat is within 300 ms following an ECG confirmed P-wave for at least 70% of the ECG confirmed P-waves. The primary endpoint will be evaluated during the MARVEL 2 setup phase during MARVEL 2 Algorithm monitor mode (VDI pacing which is effectively VVI pacing) and during the 20-minute resting period in which the MARVEL 2 Algorithm is programmed to Adaptive mode (VDD pacing)</description>
          <population>Participants with a predominant heart rhythm of 3rd degree atrioventricular block and normal sinus function during the study period.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Monitor Mode Success and Adaptive Mode Success</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Monitor Mode Failed and Adaptive Mode Success</title>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Monitor Mode Success and Adaptive Mode Fail</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Monitor Mode Fail and Adaptive Mode Fail</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis was that the probability of meeting the endpoint (Atrioventricular synchrony &gt;70%) was the same in MARVEL 2 Monitor Mode and MARVEL 2 Adaptive Mode. A sample size of 35 participants with a predominant rhythm of 3rd degree atrioventricular block and normal sinus function provided &gt;90% power at a type I error rate of 0.05 assuming the proportion of patients meeting the endpoint in one mode, but not the other exceeded 50% and 90% of these pairs favored the Adaptive mode.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>McNemar</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Free From Inappropriate Pacemaker Function Events</title>
        <description>A participant will meet the primary endpoint if they are free from the following MARVEL 2 software related events during the entire Holter monitoring period where the MARVEL 2 features are enabled.&#xD;
Inappropriate pacemaker function events are defined as:&#xD;
Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR&#xD;
Pacemaker oversensing induced tachycardia exceeding 3-minutes, defined as oversensing of the pacemaker's accelerometer signal leading to a heart rate exceeding 100 beats per minute.</description>
        <time_frame>Through study completion an average of one day</time_frame>
        <population>Number of participants with the MARVEL 2 software downloaded onto their Micra implanted pacemaker</population>
        <group_list>
          <group group_id="O1">
            <title>MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive Mode</title>
            <description>Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Free From Inappropriate Pacemaker Function Events</title>
          <description>A participant will meet the primary endpoint if they are free from the following MARVEL 2 software related events during the entire Holter monitoring period where the MARVEL 2 features are enabled.&#xD;
Inappropriate pacemaker function events are defined as:&#xD;
Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR&#xD;
Pacemaker oversensing induced tachycardia exceeding 3-minutes, defined as oversensing of the pacemaker's accelerometer signal leading to a heart rate exceeding 100 beats per minute.</description>
          <population>Number of participants with the MARVEL 2 software downloaded onto their Micra implanted pacemaker</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis is that 87% or fewer participants will achieve the endpoint. The alternative hypothesis is that more than 87% of participants will achieve the endpoint. A sample size of 70 participants provides at least 90% power to test the null hypothesis assuming the true rate of meeting the endpoint in the population is 98% at a type I error rate of 2.5%.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Exact binomial test</method>
            <param_type>proportion expressed as a percentage</param_type>
            <param_value>100</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>95.2</ci_lower_limit>
            <ci_upper_limit>100</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Left Ventricular Outflow Tract Velocity Time Integral</title>
        <description>The secondary endpoint is left ventricular outflow tract (LVOT) velocity time integral (VTI) as obtained from echocardiogram while the MARVEL 2 features are in adaptive mode (VDD pacing) and while the MARVEL 2 features are in monitor mode (VDI pacing which is effectively VVI pacing). This was measured by the echo core laboratory that was blinded to the study participant and MARVEL 2 algorithm mode.</description>
        <time_frame>12 cardiac cycles</time_frame>
        <population>Participants with paired LVOT VTI measurements during MARVEL 2 Adaptive mode (VDD pacing mode) and MARVEL 2 Monitor mode (VDI pacing which is effectively VVI pacing) with a predominant heart rhythm of persistent 3rd degree atrioventricular block and normal sinus rhythm</population>
        <group_list>
          <group group_id="O1">
            <title>MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive Mode</title>
            <description>Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Left Ventricular Outflow Tract Velocity Time Integral</title>
          <description>The secondary endpoint is left ventricular outflow tract (LVOT) velocity time integral (VTI) as obtained from echocardiogram while the MARVEL 2 features are in adaptive mode (VDD pacing) and while the MARVEL 2 features are in monitor mode (VDI pacing which is effectively VVI pacing). This was measured by the echo core laboratory that was blinded to the study participant and MARVEL 2 algorithm mode.</description>
          <population>Participants with paired LVOT VTI measurements during MARVEL 2 Adaptive mode (VDD pacing mode) and MARVEL 2 Monitor mode (VDI pacing which is effectively VVI pacing) with a predominant heart rhythm of persistent 3rd degree atrioventricular block and normal sinus rhythm</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" lower_limit="0.7" upper_limit="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis is that the mean LVOT VTI during MARVEL 2 Adaptive mode equals the mean LVOT VTI during MARVEL 2 Monitor mode. A sample size of 35 participants with paired LVOT VTI measurements provides 89% power at a type I error rate of 5% to reject the null hypothesis assuming the true difference in LVOT VTI is 2.1 cm with a standard deviation of 3.8 cm.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired t-test since each participant had LVOT VTI measurements in MARVEL 2 Adaptive and Monitor modes</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.7</ci_lower_limit>
            <ci_upper_limit>2.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 day</time_frame>
      <group_list>
        <group group_id="E1">
          <title>MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive Mode</title>
          <description>Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</default_vocab>
        <default_assessment>Non-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="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Myocardial haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 22.0</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="3" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tricuspid valve incompetence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="75"/>
              </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>In most cases, the contract allows the principal investigator to publish their data after release of a multi-center publication per the publication strategy following Medtronic's review for disclosure of confidential information (&quot;CI&quot;), technical correctness, disclosure of patentable or copyrightable material, and selection and order of publications by the publications committee. Any such CI and/or item identified as not technically correct is deleted prior to publication/presentation.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dana Wigert, Sr Prin Clinical Research Specialist</name_or_title>
      <organization>Medtronic, Plc</organization>
      <phone>+17635262802</phone>
      <email>dana.wigert@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/NCT03752151
org study id: MDT18024
nct id: NCT03752151
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The purpose of the Micra Atrial TRacking Using A Ventricular AccELerometer 2 (MARVEL 2) study
      is to demonstrate safe and effective operation of the MARVEL 2 features for providing AV
      synchronous pacing in patients with normal sinus node function and AV block
The MARVEL 2 study is an acute, prospective, global, multi-center, software-download clinical
      study. The study is planned to be conducted in US, Europe, and Asia. The study is expected to
      be conducted at approximately 15-20 centers in up to 100 subjects to obtain at least 70
      usable Holter datasets to meet the objectives of the study. The expected total study duration
      (from first subject enrollment to the exit of the last subject) is approximately 6-months;
      this represents the time necessary to enroll the target sample size of at least 70 subjects
      with usable Holter datasets. Software will be downloaded into patients implanted with a Micra
      device to allow the new algorithm performance to be measured in patients where a Micra device
      has already been chosen as most appropriate for the patient.

      Most enrolled subjects will complete the study procedures during a single study visit.
      However, subjects enrolling in the study at the time of their Micra implant (anticipated to
      be approximately 10 subjects) will have the investigational algorithm downloaded following
      Micra implant, prior to hospital discharge, and approximately 1-month post-implant. This
      subset of subjects with de novo Micra implants will allow the MARVEL 2 features to be tested
      at multiple points in the device life cycle.

      Since the download algorithm running in a Micra device significantly increases current drain,
      a 2-4 hour acute study is used to limit the reduction in device longevity.
intervention model: Sequential Assignment
intervention model description: Subjects enrolled in the MARVEL 2 study. Enrolled subjects will have the MARVEL 2 algorithm downloaded into their implanted market released Micra device. Each subject will be tested during when the MARVEL 2 algorithm is in monitor mode (VVI pacing) and in adaptive mode (VDD pacing).
primary purpose: Treatment
masking: None (Open Label)
masking description: Echocardiogram core lab will be masked to the individual patient subjects and MARVEL 2 algorithm mode.
measure: Atrial Ventricular Pacing Synchrony Success During Rest
time frame: 40 Minutes
description: A subject will meet the primary endpoint if a paced or sensed ventricular beat is within 300 ms following an ECG confirmed P-wave for at least 70% of the ECG confirmed P-waves. The primary endpoint will be evaluated during the MARVEL 2 setup phase during MARVEL 2 Algorithm monitor mode (VDI pacing which is effectively VVI pacing) and during the 20-minute resting period in which the MARVEL 2 Algorithm is programmed to Adaptive mode (VDD pacing)
measure: Number of Participants Free From Inappropriate Pacemaker Function Events
time frame: Through study completion an average of one day
description: A participant will meet the primary endpoint if they are free from the following MARVEL 2 software related events during the entire Holter monitoring period where the MARVEL 2 features are enabled.
Inappropriate pacemaker function events are defined as:
Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR
Pacemaker oversensing induced tachycardia exceeding 3-minutes, defined as oversensing of the pacemaker's accelerometer signal leading to a heart rate exceeding 100 beats per minute.
measure: Left Ventricular Outflow Tract Velocity Time Integral
time frame: 12 cardiac cycles
description: The secondary endpoint is left ventricular outflow tract (LVOT) velocity time integral (VTI) as obtained from echocardiogram while the MARVEL 2 features are in adaptive mode (VDD pacing) and while the MARVEL 2 features are in monitor mode (VDI pacing which is effectively VVI pacing). This was measured by the echo core laboratory that was blinded to the study participant and MARVEL 2 algorithm mode.
arm group label: MARVEL 2 Algorithm Monitor Mode, Then MARVEL 2 Adaptive Mode
arm group type: Experimental
description: Participants first received MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes followed by MARVEL 2 algorithm adaptive mode for approximately 2 hours which provides VDD pacing.
intervention type: Device
intervention name: MARVEL 2 Algorithm Monitor Mode then Adaptive Mode
description: Software download into implanted Micra device and programmed to MARVEL 2 Monitor Mode then MARVEL 2 Adaptive Mode
arm group label: MARVEL 2 Algorithm Monitor Mode, Then MARVEL 2 Adaptive Mode
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Belgium
country: Denmark
country: France
country: Hong Kong
country: Malaysia
country: Spain
country: United States
country: Czechia
country: Italy
responsible party type: Sponsor
mesh term: Heart Block
mesh term: Atrioventricular Block
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 