<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/NCT02211456</url>
  </required_header>
  <id_info>
    <org_study_id>DOUBLE-CRT_72014</org_study_id>
    <nct_id>NCT02211456</nct_id>
  </id_info>
  <brief_title>An Assessment of Dual Site Left Ventricular Endocardial Pacing</brief_title>
  <acronym>DOUBLE-CRT</acronym>
  <official_title>Dual Site Left Endocardial Pacing for Cardiac Resynchronisation Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oxford University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oxford University Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We are investigating ways to help patients with heart failure, which is caused by damaged&#xD;
      hearts which function less well, and cause symptoms of breathlessness, fatigue, lack of&#xD;
      energy and swelling.&#xD;
&#xD;
      Cardiac Resynchronisation Therapy (CRT) pacemakers are used to improve the pumping function&#xD;
      of the main heart chamber in certain suitable people with heart failure. CRT requires a&#xD;
      pacemaker with 2 wires, one placed inside the right heart chamber and one normally placed on&#xD;
      the outside of the left heart chamber. These two wires act together to re-time the&#xD;
      coordination of the heartbeat, which is known to improve heart function.&#xD;
&#xD;
      The investigators are assessing whether they might be able to improve heart function even&#xD;
      more by placing two wires on the inside of the left heart chamber, rather than one around the&#xD;
      outside.&#xD;
&#xD;
      The investigators wish to assess whether:&#xD;
&#xD;
        1. Using two wires within the left side of the heart gives a greater increase in heart&#xD;
           function than one.&#xD;
&#xD;
        2. It is possible to choose the best spot inside of the heart by measuring the pattern of&#xD;
           the heart beat.&#xD;
&#xD;
        3. Is it possible to use a different type of heart monitor placed outside the body instead&#xD;
           of a monitor wire inside the heart to assess improvement in heart function? They are&#xD;
           investigating this in people with hearts that beat less effectively than normal.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute Haemodynamic Response to Dual Left Ventricular Pacing</measure>
    <time_frame>Mean of multiple recordings in each patient as detailed above</time_frame>
    <description>Acute haemodynamic response to pacing (change in Left Ventricular dP/dt max) between dual site Left Ventricular pacing and biventricular pacing Pacing protocols were performed with a baseline of 30 seconds of right ventricular pacing followed by two 30-second test configurations, and then a further baseline. The pacing configurations were tested, in a randomized order, 3 times each.&#xD;
Electrophysiology catheters were positioned at the right ventricular mid septum for baseline pacing, and at the left ventricular septum and at the left ventricular lateral wall, at the site of latest electrical activation i identified from a left ventricular electrical activation map This provided two single-site left ventricular pacing configurations, which could be combined to allow right ventricular and left ventricular lateral (Biventricular pacing) and left ventricular septal and left ventricular lateral (dual left ventricular pacing)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Ventricular Tachycardia</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Having an ablation procedure with access to the left side of the heart</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Atrial Fibrillation/flutter (AF) or Ventricular Tachycardia (VT) ablation with multi-site pacing protocol</intervention_name>
    <description>Pacing at several endocardial sites in isolation and individually will be performed, with response to this assessed by LV dp/dt max</description>
    <arm_group_label>Participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is willing and able to give informed consent for participation in the&#xD;
             study.&#xD;
&#xD;
          -  Male or Female, aged 60 years or above.&#xD;
&#xD;
          -  Having a suitable Atrial Fibrillation/flutter or Ventricular Tachycardia ablation&#xD;
             procedure&#xD;
&#xD;
          -  Evidence of abnormal Left Ventricular structure and function, as shown by Left&#xD;
             Ventricular ejection fraction of less than 40%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe peripheral vascular disease (that would make arterial access more risky)&#xD;
&#xD;
          -  Haemodynamic instability (such that a longer procedure is inadvisable)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim R Betts, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oxford University Hospitals NHS Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oxford University Hospitals NHS Trust</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 7AT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Bordachar P, Derval N, Ploux S, Garrigue S, Ritter P, Haissaguerre M, Jais P. Left ventricular endocardial stimulation for severe heart failure. J Am Coll Cardiol. 2010 Aug 31;56(10):747-53. doi: 10.1016/j.jacc.2010.04.038.</citation>
    <PMID>20797486</PMID>
  </reference>
  <reference>
    <citation>Shetty AK, Sohal M, Chen Z, Ginks MR, Bostock J, Amraoui S, Ryu K, Rosenberg SP, Niederer SA, Gill J, Carr-White G, Razavi R, Rinaldi CA. A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study. Europace. 2014 Jun;16(6):873-9. doi: 10.1093/europace/eut420. Epub 2014 Feb 12.</citation>
    <PMID>24525553</PMID>
  </reference>
  <reference>
    <citation>Rogers DP, Lambiase PD, Lowe MD, Chow AW. A randomized double-blind crossover trial of triventricular versus biventricular pacing in heart failure. Eur J Heart Fail. 2012 May;14(5):495-505. doi: 10.1093/eurjhf/hfs004. Epub 2012 Feb 6.</citation>
    <PMID>22312038</PMID>
  </reference>
  <reference>
    <citation>Betts TR, Gamble JH, Khiani R, Bashir Y, Rajappan K. Development of a technique for left ventricular endocardial pacing via puncture of the interventricular septum. Circ Arrhythm Electrophysiol. 2014 Feb;7(1):17-22. doi: 10.1161/CIRCEP.113.001110. Epub 2014 Jan 14.</citation>
    <PMID>24425419</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 1, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <results_first_submitted>May 19, 2020</results_first_submitted>
  <results_first_submitted_qc>February 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 4, 2021</results_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oxford University Hospitals NHS Trust</investigator_affiliation>
    <investigator_full_name>Dr James Gamble</investigator_full_name>
    <investigator_title>Research Fellow</investigator_title>
  </responsible_party>
  <keyword>Endocardial pacing</keyword>
  <keyword>Multi site pacing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Tachycardia, Ventricular</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Participants</title>
          <description>Having an ablation procedure with access to the left side of the heart&#xD;
Atrial Fibrillation/flutter (AF) or Ventricular Tachycardia (VT) ablation with multi-site pacing protocol: Pacing at several endocardial sites in isolation and individually will be performed, with response to this assessed by LV dp/dt max&#xD;
All patients underwent the pacing protocol</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Participants</title>
          <description>Having an ablation procedure with access to the left side of the heart&#xD;
Atrial Fibrillation/flutter (AF) or Ventricular Tachycardia (VT) ablation with multi-site pacing protocol: Pacing at several endocardial sites in isolation and individually will be performed, with response to this assessed by LV dp/dt max</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </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="68" spread="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ischaemic aetiology of left ventricular dysfunction</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Left ventricular ejection fraction</title>
          <units>%</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27" spread="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Acute Haemodynamic Response to Dual Left Ventricular Pacing</title>
        <description>Acute haemodynamic response to pacing (change in Left Ventricular dP/dt max) between dual site Left Ventricular pacing and biventricular pacing Pacing protocols were performed with a baseline of 30 seconds of right ventricular pacing followed by two 30-second test configurations, and then a further baseline. The pacing configurations were tested, in a randomized order, 3 times each.&#xD;
Electrophysiology catheters were positioned at the right ventricular mid septum for baseline pacing, and at the left ventricular septum and at the left ventricular lateral wall, at the site of latest electrical activation i identified from a left ventricular electrical activation map This provided two single-site left ventricular pacing configurations, which could be combined to allow right ventricular and left ventricular lateral (Biventricular pacing) and left ventricular septal and left ventricular lateral (dual left ventricular pacing)</description>
        <time_frame>Mean of multiple recordings in each patient as detailed above</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Having an ablation procedure with access to the left side of the heart&#xD;
Atrial Fibrillation/flutter (AF) or Ventricular Tachycardia (VT) ablation with multi-site pacing protocol: Pacing at several endocardial sites in isolation and individually will be performed, with response to this assessed by LV dp/dt max</description>
          </group>
        </group_list>
        <measure>
          <title>Acute Haemodynamic Response to Dual Left Ventricular Pacing</title>
          <description>Acute haemodynamic response to pacing (change in Left Ventricular dP/dt max) between dual site Left Ventricular pacing and biventricular pacing Pacing protocols were performed with a baseline of 30 seconds of right ventricular pacing followed by two 30-second test configurations, and then a further baseline. The pacing configurations were tested, in a randomized order, 3 times each.&#xD;
Electrophysiology catheters were positioned at the right ventricular mid septum for baseline pacing, and at the left ventricular septum and at the left ventricular lateral wall, at the site of latest electrical activation i identified from a left ventricular electrical activation map This provided two single-site left ventricular pacing configurations, which could be combined to allow right ventricular and left ventricular lateral (Biventricular pacing) and left ventricular septal and left ventricular lateral (dual left ventricular pacing)</description>
          <units>% difference</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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" lower_limit="1.0" upper_limit="6.3"/>
                  </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 data derived from this study was complex multi-level data with errors due to patient-level and intra-patient repeat factors. Accordingly, we used generalized multi-level modelling (GLMM) with random effects.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>3.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1</ci_lower_limit>
            <ci_upper_limit>6.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Participants</title>
          <description>Having an ablation procedure with access to the left side of the heart&#xD;
Atrial Fibrillation/flutter (AF) or Ventricular Tachycardia (VT) ablation with multi-site pacing protocol: Pacing at several endocardial sites in isolation and individually will be performed, with response to this assessed by LV dp/dt max</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke</sub_title>
                <description>One patient developed neurological symptoms shortly after waking up from anesthesia after his ventricular tachycardia ablation and was found to have had a left sided stroke.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr James Gamble</name_or_title>
      <organization>Oxford University Hospitals NHS FT</organization>
      <phone>00441865221012</phone>
      <email>james.gamble@ouh.nhs.uk</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/NCT02211456
org study id: DOUBLE-CRT_72014
nct id: NCT02211456
lead sponsor: 
has dmc: Yes
We are investigating ways to help patients with heart failure, which is caused by damaged
      hearts which function less well, and cause symptoms of breathlessness, fatigue, lack of
      energy and swelling.

      Cardiac Resynchronisation Therapy (CRT) pacemakers are used to improve the pumping function
      of the main heart chamber in certain suitable people with heart failure. CRT requires a
      pacemaker with 2 wires, one placed inside the right heart chamber and one normally placed on
      the outside of the left heart chamber. These two wires act together to re-time the
      coordination of the heartbeat, which is known to improve heart function.

      The investigators are assessing whether they might be able to improve heart function even
      more by placing two wires on the inside of the left heart chamber, rather than one around the
      outside.

      The investigators wish to assess whether:

        1. Using two wires within the left side of the heart gives a greater increase in heart
           function than one.

        2. It is possible to choose the best spot inside of the heart by measuring the pattern of
           the heart beat.

        3. Is it possible to use a different type of heart monitor placed outside the body instead
           of a monitor wire inside the heart to assess improvement in heart function? They are
           investigating this in people with hearts that beat less effectively than normal.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Acute Haemodynamic Response to Dual Left Ventricular Pacing
time frame: Mean of multiple recordings in each patient as detailed above
description: Acute haemodynamic response to pacing (change in Left Ventricular dP/dt max) between dual site Left Ventricular pacing and biventricular pacing Pacing protocols were performed with a baseline of 30 seconds of right ventricular pacing followed by two 30-second test configurations, and then a further baseline. The pacing configurations were tested, in a randomized order, 3 times each.
Electrophysiology catheters were positioned at the right ventricular mid septum for baseline pacing, and at the left ventricular septum and at the left ventricular lateral wall, at the site of latest electrical activation i identified from a left ventricular electrical activation map This provided two single-site left ventricular pacing configurations, which could be combined to allow right ventricular and left ventricular lateral (Biventricular pacing) and left ventricular septal and left ventricular lateral (dual left ventricular pacing)
arm group label: Participants
arm group type: Experimental
description: Having an ablation procedure with access to the left side of the heart
intervention type: Procedure
intervention name: Atrial Fibrillation/flutter (AF) or Ventricular Tachycardia (VT) ablation with multi-site pacing protocol
description: Pacing at several endocardial sites in isolation and individually will be performed, with response to this assessed by LV dp/dt max
arm group label: Participants
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: No
last name: Tim R Betts, MD
role: Principal Investigator
affiliation: Oxford University Hospitals NHS Trust
facility: 
country: United Kingdom
citation: Bordachar P, Derval N, Ploux S, Garrigue S, Ritter P, Haissaguerre M, Jais P. Left ventricular endocardial stimulation for severe heart failure. J Am Coll Cardiol. 2010 Aug 31;56(10):747-53. doi: 10.1016/j.jacc.2010.04.038.
PMID: 20797486
citation: Shetty AK, Sohal M, Chen Z, Ginks MR, Bostock J, Amraoui S, Ryu K, Rosenberg SP, Niederer SA, Gill J, Carr-White G, Razavi R, Rinaldi CA. A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study. Europace. 2014 Jun;16(6):873-9. doi: 10.1093/europace/eut420. Epub 2014 Feb 12.
PMID: 24525553
citation: Rogers DP, Lambiase PD, Lowe MD, Chow AW. A randomized double-blind crossover trial of triventricular versus biventricular pacing in heart failure. Eur J Heart Fail. 2012 May;14(5):495-505. doi: 10.1093/eurjhf/hfs004. Epub 2012 Feb 6.
PMID: 22312038
citation: Betts TR, Gamble JH, Khiani R, Bashir Y, Rajappan K. Development of a technique for left ventricular endocardial pacing via puncture of the interventricular septum. Circ Arrhythm Electrophysiol. 2014 Feb;7(1):17-22. doi: 10.1161/CIRCEP.113.001110. Epub 2014 Jan 14.
PMID: 24425419
responsible party type: Principal Investigator
investigator affiliation: Oxford University Hospitals NHS Trust
investigator full name: Dr James Gamble
investigator title: Research Fellow
mesh term: Atrial Fibrillation
mesh term: Tachycardia
mesh term: Tachycardia, Ventricular
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 