<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/NCT03769272</url>
  </required_header>
  <id_info>
    <org_study_id>227862</org_study_id>
    <nct_id>NCT03769272</nct_id>
  </id_info>
  <brief_title>Optimal Left Ventricular Lead Positioning During Cardiac Resynchronisation Therapy; Comparison of Two Methods of Targeting</brief_title>
  <official_title>Optimal Left Ventricular Lead Positioning During Cardiac Resynchronisation Therapy; Comparison of Two Methods of Targeting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter J Pugh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cambridge University Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cardiac Resynchronisation Therapy (CRT) is a well-known treatment for patients with heart&#xD;
      failure. It is a special pacemaker that consists of three pacing wires, which are implanted&#xD;
      in the right upper and bottom chambers of the heart and via a vein on the surface of the main&#xD;
      pumping chamber (left bottom chamber). CRT helps by improving co- ordination between the top&#xD;
      and the bottom chambers of the heart. By stimulating the heart from the left and right bottom&#xD;
      chambers, co-ordination can be restored and heart function as well as symptoms improve. It is&#xD;
      known that up to 30-40% of patients of patients undergoing CRT pacemaker implantation do not&#xD;
      attain any benefit. Given the inherent risks and costs of pacemaker implantation and&#xD;
      maintenance, a reduction in the rate of CRT &quot;non-responders&quot; is an important goal.&#xD;
&#xD;
      It has been suggested that presence of scar tissue in the heart and suboptimal placement of&#xD;
      the pacing wire on the top of the main pumping chamber can explain this poor response. The&#xD;
      best place to position the pacing wire on the surface of the main pumping chamber is the area&#xD;
      that contracts last and it can be identified using ultrasound scan of the heart.&#xD;
&#xD;
      Unfortunately, ultrasound is not always possible to help identifying the best area and only a&#xD;
      minority of hospitals are able to use this method. Therefore we aim to investigate&#xD;
      alternative ways of positioning the pacing wire in the best possible area of the main pumping&#xD;
      heart chamber. Investigators propose to measure electrical signals as an alternative and more&#xD;
      effective way in positioning the wire in the most effective area. Investigators aim to look&#xD;
      at the relationship between the best area identified by ultrasound scan and by electrical&#xD;
      signals and also use electrical signals to avoid areas of scar.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiac Resynchronisation Therapy (CRT) reduces both morbidity and mortality in selected&#xD;
      patients with left ventricular dysfunction and intraventricular conduction delay who remain&#xD;
      symptomatic despite optimal medical therapy.&#xD;
&#xD;
      It is known that up to 30% of patients of patients undergoing CRT implantation do not attain&#xD;
      symptomatic benefit . Given the inherent risks and costs of device implantation and&#xD;
      maintenance, a reduction in the rate of CRT &quot;non-responders&quot; is an important goal.&#xD;
&#xD;
      Factors associated with a poor outcome include presence of myocardial scar, and suboptimal&#xD;
      Left Ventricular (LV) lead placement.&#xD;
&#xD;
      Pacing the LV at the most delayed LV region promotes contractile synchrony resulting in more&#xD;
      effective and energetically efficient ejection, geometric remodelling with reduced LV&#xD;
      end-systolic volume and improved cardiac function.&#xD;
&#xD;
      Studies using transthoracic echocardiographic (TTE) parameters to target the LV lead&#xD;
      positioning have shown that an optimal LV lead position at the site of latest mechanical&#xD;
      activation, avoiding low strain amplitude (scar), was associated with superior response to&#xD;
      CRT and improved survival that persisted during follow-up.&#xD;
&#xD;
      It remains unclear whether the site of latest mechanical activation is related to the site of&#xD;
      latest electrical activation, nor whether sensed electrical signals correspond to sites of&#xD;
      scar. The site of latest electrical activation is assessed during CRT implant by measuring&#xD;
      electrical activation (LV electrical delay) of the LV at different sites in relation to the&#xD;
      first deflection of the QRS complex of the surface electrocardiogram (ECG).&#xD;
&#xD;
      A recent study evaluated the relationship between LV electrical delay and CRT outcomes/&#xD;
      response to CRT and concluded that electrical dyssynchrony was strongly and independently&#xD;
      associated with reverse remodelling and led to improvement in the Quality of Life with CRT.&#xD;
&#xD;
      Despite TTE being an effective way of assessing optimal LV lead positioning for identifying&#xD;
      mechanical activation, it is expensive, images can be suboptimal and usually requires an&#xD;
      extra visit prior to implantation, therefore an intraprocedural way of identifying the&#xD;
      optimal areas could be beneficial.&#xD;
&#xD;
      It is not known whether lead position as targeted by imaging methods of mechanical activation&#xD;
      corresponds to the site of latest electrical activation, nor whether sensed electrical&#xD;
      signals correspond to sites of scar. Investigators are planning to investigate the&#xD;
      relationship between the site of latest mechanical activation using TTE and the site of&#xD;
      latest electrical activation of the LV; and between scar and sensed electrical signals.&#xD;
&#xD;
      If the area of latest mechanical activation is related to the area of latest electrical&#xD;
      activation then this can be an alternative, more convenient and cost effective way of&#xD;
      assessing optimal LV lead positioning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 1, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Q-LV (electrical activation of the left ventricle) at different sites of the left ventricle</measure>
    <time_frame>1 day</time_frame>
    <description>The time from onset of depolarisation (Q wave) to sensed electrogram in the left ventricle (&quot;LV&quot;) will be measured at various sites over the left ventricular epicardium to build up a map of myocardial electrical activation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mechanical activation of the left ventricle using echocardiography</measure>
    <time_frame>1 day</time_frame>
    <description>The pattern of mechanical activation of the left ventricle will be determined using speckle-tracking echocardiography.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Echocardiographic targeting</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Electrogram targeting</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Measurement of electrical delay during LV lead placement</intervention_name>
    <description>Measurement of electrical signal in the heart during implantation of CRT, by positioning the lead in different places in the heart.</description>
    <arm_group_label>Electrogram targeting</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with HF, LBBB and have been referred for CRT.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. LV Ejection Fraction ≤ 35 %&#xD;
&#xD;
          2. New York Heart Association class I-IV&#xD;
&#xD;
          3. QRS ≥130ms&#xD;
&#xD;
          4. Left Bundle Branch Block&#xD;
&#xD;
          5. Male or female, aged 18 years or above&#xD;
&#xD;
          6. Able to give consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with Atrial Fibrillation&#xD;
&#xD;
          2. Unable to give consent&#xD;
&#xD;
          3. QRS≤120 ms&#xD;
&#xD;
          4. Right Bundle Branch Block&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>August 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>July 3, 2019</last_update_submitted>
  <last_update_submitted_qc>July 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Peter J Pugh</investigator_full_name>
    <investigator_title>Consultant Cardiologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03769272
org study id: 227862
nct id: NCT03769272
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Cardiac Resynchronisation Therapy (CRT) is a well-known treatment for patients with heart
      failure. It is a special pacemaker that consists of three pacing wires, which are implanted
      in the right upper and bottom chambers of the heart and via a vein on the surface of the main
      pumping chamber (left bottom chamber). CRT helps by improving co- ordination between the top
      and the bottom chambers of the heart. By stimulating the heart from the left and right bottom
      chambers, co-ordination can be restored and heart function as well as symptoms improve. It is
      known that up to 30-40% of patients of patients undergoing CRT pacemaker implantation do not
      attain any benefit. Given the inherent risks and costs of pacemaker implantation and
      maintenance, a reduction in the rate of CRT "non-responders" is an important goal.

      It has been suggested that presence of scar tissue in the heart and suboptimal placement of
      the pacing wire on the top of the main pumping chamber can explain this poor response. The
      best place to position the pacing wire on the surface of the main pumping chamber is the area
      that contracts last and it can be identified using ultrasound scan of the heart.

      Unfortunately, ultrasound is not always possible to help identifying the best area and only a
      minority of hospitals are able to use this method. Therefore we aim to investigate
      alternative ways of positioning the pacing wire in the best possible area of the main pumping
      heart chamber. Investigators propose to measure electrical signals as an alternative and more
      effective way in positioning the wire in the most effective area. Investigators aim to look
      at the relationship between the best area identified by ultrasound scan and by electrical
      signals and also use electrical signals to avoid areas of scar.
Cardiac Resynchronisation Therapy (CRT) reduces both morbidity and mortality in selected
      patients with left ventricular dysfunction and intraventricular conduction delay who remain
      symptomatic despite optimal medical therapy.

      It is known that up to 30% of patients of patients undergoing CRT implantation do not attain
      symptomatic benefit . Given the inherent risks and costs of device implantation and
      maintenance, a reduction in the rate of CRT "non-responders" is an important goal.

      Factors associated with a poor outcome include presence of myocardial scar, and suboptimal
      Left Ventricular (LV) lead placement.

      Pacing the LV at the most delayed LV region promotes contractile synchrony resulting in more
      effective and energetically efficient ejection, geometric remodelling with reduced LV
      end-systolic volume and improved cardiac function.

      Studies using transthoracic echocardiographic (TTE) parameters to target the LV lead
      positioning have shown that an optimal LV lead position at the site of latest mechanical
      activation, avoiding low strain amplitude (scar), was associated with superior response to
      CRT and improved survival that persisted during follow-up.

      It remains unclear whether the site of latest mechanical activation is related to the site of
      latest electrical activation, nor whether sensed electrical signals correspond to sites of
      scar. The site of latest electrical activation is assessed during CRT implant by measuring
      electrical activation (LV electrical delay) of the LV at different sites in relation to the
      first deflection of the QRS complex of the surface electrocardiogram (ECG).

      A recent study evaluated the relationship between LV electrical delay and CRT outcomes/
      response to CRT and concluded that electrical dyssynchrony was strongly and independently
      associated with reverse remodelling and led to improvement in the Quality of Life with CRT.

      Despite TTE being an effective way of assessing optimal LV lead positioning for identifying
      mechanical activation, it is expensive, images can be suboptimal and usually requires an
      extra visit prior to implantation, therefore an intraprocedural way of identifying the
      optimal areas could be beneficial.

      It is not known whether lead position as targeted by imaging methods of mechanical activation
      corresponds to the site of latest electrical activation, nor whether sensed electrical
      signals correspond to sites of scar. Investigators are planning to investigate the
      relationship between the site of latest mechanical activation using TTE and the site of
      latest electrical activation of the LV; and between scar and sensed electrical signals.

      If the area of latest mechanical activation is related to the area of latest electrical
      activation then this can be an alternative, more convenient and cost effective way of
      assessing optimal LV lead positioning.
observational model: Case-Control
time perspective: Prospective
measure: Q-LV (electrical activation of the left ventricle) at different sites of the left ventricle
time frame: 1 day
description: The time from onset of depolarisation (Q wave) to sensed electrogram in the left ventricle ("LV") will be measured at various sites over the left ventricular epicardium to build up a map of myocardial electrical activation
measure: Mechanical activation of the left ventricle using echocardiography
time frame: 1 day
description: The pattern of mechanical activation of the left ventricle will be determined using speckle-tracking echocardiography.
arm group label: Echocardiographic targeting
arm group label: Electrogram targeting
intervention type: Procedure
intervention name: Measurement of electrical delay during LV lead placement
description: Measurement of electrical signal in the heart during implantation of CRT, by positioning the lead in different places in the heart.
arm group label: Electrogram targeting
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor-Investigator
investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
investigator full name: Peter J Pugh
investigator title: Consultant Cardiologist
mesh term: Heart Failure
sharing ipd: No