<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/NCT02198781</url>
  </required_header>
  <id_info>
    <org_study_id>B729</org_study_id>
    <nct_id>NCT02198781</nct_id>
  </id_info>
  <brief_title>Right Ventricle (RV) Markers of Future Pacing Induced Ventricular Dysfunction - Pilot</brief_title>
  <official_title>Does a Measure Exist in the Right Ventricle Which Can Act as a Surrogate Marker for Future Ventriclar Sysfunction When Pacing - a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mid and South Essex NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Anglia Ruskin University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mid and South Essex NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study into the effects on heart function when pacing the right ventricle&#xD;
      (RV). This study aims to enrol a population who are clinically indicated to receive a&#xD;
      pacemaker.&#xD;
&#xD;
      When normal conduction within the heart fails, the treatment may be to implant a permanent&#xD;
      pacemaker. Pacing involves passing a lead via a vein to the heart and using an electrical&#xD;
      impulse to stimulate a beat.&#xD;
&#xD;
      Increasingly the available evidence suggests that long term RV pacing is associated with&#xD;
      complications - left ventricule (LV) dysfunction, heart failure, atrial fibrillation (AF) and&#xD;
      death in some patients. What we do not see are a large proportion of all patients who receive&#xD;
      pacemakers suffering pacing related adverse effects.&#xD;
&#xD;
      If there could be a way of identifying those patients in the group who go on to develop&#xD;
      pacing induced cardiomyopathy at the time of initial pacing implant, this would be a very&#xD;
      valuable clinical measure. These patients could be identified from the outset and paced with&#xD;
      a biventricular device to avoid the pacing induced cardiomyopathy. Whilst much energy has&#xD;
      been directed towards the LV as a focus of the clinical markers of disease, little has been&#xD;
      published looking at RV haemodynamics.&#xD;
&#xD;
      We plan to study a cohort of patients who are clinically indicated to receive a pacemaker and&#xD;
      study their RV in detail at the time of implantation. We will use conductance catheters and&#xD;
      echocardiography to determine measures of pumping function. We will then follow them up for a&#xD;
      period of six month using echocardiography and blood markers of heart dysfunction. In those&#xD;
      patients who have a reduction in heart function we will then look for common patterns within&#xD;
      their initial measurements.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed to explore whether a marker exists within the right ventricle (RV)&#xD;
      that may suggest future pacing induced dysfunction of the heart. Pacing the heart is a&#xD;
      necessary procedure when normal conduction has failed. It has been shown in some patients to&#xD;
      result in deleterious effects on the pumping function of the left ventricle acutely and&#xD;
      chronically. Little has been looked into within right ventricular function and how this&#xD;
      interacts with the left side. The fact that this dysfunction is not seen in all patients who&#xD;
      receive pacemakers is important and we aim to use these pure haemodynamic measures to&#xD;
      investigate this issue and try to identify those patients who may go on to have pacing&#xD;
      induced dysfunction. This is an important scientific question to answer as we know that these&#xD;
      patients can be spared the ventricular dysfunction by the intervention of biventricular&#xD;
      pacing at the time of initial implantation. What we do not know is how to choose this group&#xD;
      at the outset.&#xD;
&#xD;
      The study has been designed as a pilot investigation using patients who are to undergo&#xD;
      permanent pacemaker therapy. Our study will entail one additional catheter being passed to&#xD;
      the heart and also one to the inferior vena cava. This measurement of heart function will be&#xD;
      performed directly after the implantation of the pacemaker and will add only a small amount&#xD;
      of time to the case.&#xD;
&#xD;
      We will then follow these patients up and take echocardiographic data as well as blood&#xD;
      markers of impaired ventricular function at 6 months.&#xD;
&#xD;
      The design of this study is that of a cohort study with the common exposure being that of&#xD;
      pacemaker therapy. We seek to take detailed haemodynamic and echocardiographic measurements&#xD;
      at the time of implantation. This will yield powerful data when cross referenced to cases of&#xD;
      adverse ventricular function seen due to pacing at follow up. We aim to perform this pilot&#xD;
      study as a feasibility process in order to ascertain the frequency of measurable adverse&#xD;
      effects in this population and gain early insights into the markers we can look for. We do&#xD;
      not know this data at present. This will allow for a future definitive study to be designed&#xD;
      with appropriate participant numbers and follow up periods. The follow up period of 6 months&#xD;
      has been set in order to fit within the time constraints of an ongoing MD undertaking.&#xD;
&#xD;
      Patients who are being booked for a pacemaker implantation as per the normal course of their&#xD;
      treatment will be eligible to enter the study as long as they have a high anticipated pacing&#xD;
      component. This means that these patients would be expected to have their heart stimulated&#xD;
      via the pacemaker most of the time under normal circumstances of their care.&#xD;
&#xD;
      Patients are not eligible if they have atrial fibrillation (AF). This decision was made as&#xD;
      patients with AF have a very different activation pattern of the heart due to the&#xD;
      irregularity of heart rhythm and thus this would be a confounding factor to the study.&#xD;
&#xD;
      We will approach patients who meet eligibility criteria who are on the waiting list for&#xD;
      pacemaker implantation. We will explain that this is an adjunctive procedure to the Pacemaker&#xD;
      implant and purely for research purposes with no therapeutic benefit at the time of the&#xD;
      procedure. We will explain the follow up needs of the study and that there potentially is a&#xD;
      benefit to them to be followed up closely as per research protocol although this is not&#xD;
      normal clinical workflow. Any questions will be answered at that time and consent will at a&#xD;
      later time in preassessment clinic.&#xD;
&#xD;
      Written consent will be obtained prior to the study. The patients have the right to withdraw&#xD;
      from the trial at any point. Consent will be verbally reconfirmed before the procedure. This&#xD;
      process will be recorded within the medical notes at each stage.&#xD;
&#xD;
      The additional risk to the patient is insertion of the venous sheaths into the femoral vein.&#xD;
      This is performed routinely with every electrophysiology study which is a commonly performed&#xD;
      cardiac investigation. Very rarely the veins require to be repaired by a surgeon (1 in 500).&#xD;
      Bleeding or bruising may occur around the sheath. Insertion of the conductance catheter into&#xD;
      the heart may rarely (&lt;1 in 1000) cause structural damage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>surrogate marker</measure>
    <time_frame>30 minutes</time_frame>
    <description>To identify any surrogate markers for this patient cohort</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>dyssynchronous index</measure>
    <time_frame>30 minutes</time_frame>
    <description>To identify if any dyssynchronour index can be obtained in the right ventricle in this cohort</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">3</enrollment>
  <condition>Sick Sinus Syndrome</condition>
  <arm_group>
    <arm_group_label>Cohort</arm_group_label>
    <description>Basic science study</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who are due to undergo permanent pacemaker (PPM) implantation will be recruited to&#xD;
        undergo RV Pressure/Volume loop assessment and RV strain ECHO at the same time as PPM&#xD;
        implant for pilot data regarding the acute effects of RV pacing on RV haemodynamics&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient undergoing permanent pacemaker (PPM) implantation&#xD;
&#xD;
          -  Age 18-80 years old&#xD;
&#xD;
          -  High grade atrial-ventricular (AV) block&#xD;
&#xD;
          -  Preserved left ventricle (LV) systolic function on pre-procedure Echocardiogram&#xD;
             (EF&gt;45%)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Atrial Fibrillation&#xD;
&#xD;
          -  Recent myocardial infarct (MI)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Enrolment in any other study&#xD;
&#xD;
          -  Inability or refusal to comply with the follow-up schedule&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stuart Tan, MB BC, MRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mid and South Essex NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Essex Cardiothoracic Centre</name>
      <address>
        <city>Basildon</city>
        <state>Essex</state>
        <zip>SS16 5NL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>December 21, 2020</last_update_submitted>
  <last_update_submitted_qc>December 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>atrial fibrilation</keyword>
  <keyword>atrial-ventricula</keyword>
  <keyword>right ventricle</keyword>
  <keyword>left ventricle</keyword>
  <keyword>surrogate marker</keyword>
  <keyword>ventricular dysfunction</keyword>
  <keyword>pacing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ventricular Dysfunction</mesh_term>
    <mesh_term>Sick Sinus Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02198781
org study id: B729
nct id: NCT02198781
lead sponsor: 
collaborator: 
has dmc: No
This is a pilot study into the effects on heart function when pacing the right ventricle
      (RV). This study aims to enrol a population who are clinically indicated to receive a
      pacemaker.

      When normal conduction within the heart fails, the treatment may be to implant a permanent
      pacemaker. Pacing involves passing a lead via a vein to the heart and using an electrical
      impulse to stimulate a beat.

      Increasingly the available evidence suggests that long term RV pacing is associated with
      complications - left ventricule (LV) dysfunction, heart failure, atrial fibrillation (AF) and
      death in some patients. What we do not see are a large proportion of all patients who receive
      pacemakers suffering pacing related adverse effects.

      If there could be a way of identifying those patients in the group who go on to develop
      pacing induced cardiomyopathy at the time of initial pacing implant, this would be a very
      valuable clinical measure. These patients could be identified from the outset and paced with
      a biventricular device to avoid the pacing induced cardiomyopathy. Whilst much energy has
      been directed towards the LV as a focus of the clinical markers of disease, little has been
      published looking at RV haemodynamics.

      We plan to study a cohort of patients who are clinically indicated to receive a pacemaker and
      study their RV in detail at the time of implantation. We will use conductance catheters and
      echocardiography to determine measures of pumping function. We will then follow them up for a
      period of six month using echocardiography and blood markers of heart dysfunction. In those
      patients who have a reduction in heart function we will then look for common patterns within
      their initial measurements.
This study is designed to explore whether a marker exists within the right ventricle (RV)
      that may suggest future pacing induced dysfunction of the heart. Pacing the heart is a
      necessary procedure when normal conduction has failed. It has been shown in some patients to
      result in deleterious effects on the pumping function of the left ventricle acutely and
      chronically. Little has been looked into within right ventricular function and how this
      interacts with the left side. The fact that this dysfunction is not seen in all patients who
      receive pacemakers is important and we aim to use these pure haemodynamic measures to
      investigate this issue and try to identify those patients who may go on to have pacing
      induced dysfunction. This is an important scientific question to answer as we know that these
      patients can be spared the ventricular dysfunction by the intervention of biventricular
      pacing at the time of initial implantation. What we do not know is how to choose this group
      at the outset.

      The study has been designed as a pilot investigation using patients who are to undergo
      permanent pacemaker therapy. Our study will entail one additional catheter being passed to
      the heart and also one to the inferior vena cava. This measurement of heart function will be
      performed directly after the implantation of the pacemaker and will add only a small amount
      of time to the case.

      We will then follow these patients up and take echocardiographic data as well as blood
      markers of impaired ventricular function at 6 months.

      The design of this study is that of a cohort study with the common exposure being that of
      pacemaker therapy. We seek to take detailed haemodynamic and echocardiographic measurements
      at the time of implantation. This will yield powerful data when cross referenced to cases of
      adverse ventricular function seen due to pacing at follow up. We aim to perform this pilot
      study as a feasibility process in order to ascertain the frequency of measurable adverse
      effects in this population and gain early insights into the markers we can look for. We do
      not know this data at present. This will allow for a future definitive study to be designed
      with appropriate participant numbers and follow up periods. The follow up period of 6 months
      has been set in order to fit within the time constraints of an ongoing MD undertaking.

      Patients who are being booked for a pacemaker implantation as per the normal course of their
      treatment will be eligible to enter the study as long as they have a high anticipated pacing
      component. This means that these patients would be expected to have their heart stimulated
      via the pacemaker most of the time under normal circumstances of their care.

      Patients are not eligible if they have atrial fibrillation (AF). This decision was made as
      patients with AF have a very different activation pattern of the heart due to the
      irregularity of heart rhythm and thus this would be a confounding factor to the study.

      We will approach patients who meet eligibility criteria who are on the waiting list for
      pacemaker implantation. We will explain that this is an adjunctive procedure to the Pacemaker
      implant and purely for research purposes with no therapeutic benefit at the time of the
      procedure. We will explain the follow up needs of the study and that there potentially is a
      benefit to them to be followed up closely as per research protocol although this is not
      normal clinical workflow. Any questions will be answered at that time and consent will at a
      later time in preassessment clinic.

      Written consent will be obtained prior to the study. The patients have the right to withdraw
      from the trial at any point. Consent will be verbally reconfirmed before the procedure. This
      process will be recorded within the medical notes at each stage.

      The additional risk to the patient is insertion of the venous sheaths into the femoral vein.
      This is performed routinely with every electrophysiology study which is a commonly performed
      cardiac investigation. Very rarely the veins require to be repaired by a surgeon (1 in 500).
      Bleeding or bruising may occur around the sheath. Insertion of the conductance catheter into
      the heart may rarely (<1 in 1000) cause structural damage.
observational model: Cohort
time perspective: Prospective
measure: surrogate marker
time frame: 30 minutes
description: To identify any surrogate markers for this patient cohort
measure: dyssynchronous index
time frame: 30 minutes
description: To identify if any dyssynchronour index can be obtained in the right ventricle in this cohort
arm group label: Cohort
description: Basic science study
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Stuart Tan, MB BC, MRCP
role: Principal Investigator
affiliation: Mid and South Essex NHS Foundation Trust
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Ventricular Dysfunction
mesh term: Sick Sinus Syndrome
sharing ipd: Undecided