<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/NCT04416958</url>
  </required_header>
  <id_info>
    <org_study_id>Pace_Cond_KHF</org_study_id>
    <nct_id>NCT04416958</nct_id>
  </id_info>
  <brief_title>Pacing to Maintain Physiologic Ventricular Activation</brief_title>
  <acronym>Pace-Conduct</acronym>
  <official_title>Pacing for Cardiac Resynchronisation Using the Intrinsic Conduction System to Maintain Physiologic Ventricular Activation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Klinikum-Fuerth</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Erlangen-Nürnberg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Trieste</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Klinikum-Fuerth</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Right ventricular pacing causes ventricular dyssynchrony and may be associated with impaired&#xD;
      outcome. In the last decade, several approaches for more physiological pacing became&#xD;
      available and were implemented in the latest guidelines. However, compared to conventional&#xD;
      device implantation, cardiac resynchronization, His bundle pacing and left bundle area pacing&#xD;
      remain demanding procedures in the individual case. Goal of the single center observational&#xD;
      &quot;Pace conduct&quot; study is to evaluate implantation success, safety and outcome of pacing&#xD;
      methods that maintain physiologic ventricular activation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Conventional ectopic myocardial right ventricular pacing (RVP) causes ventricular&#xD;
      dyssynchrony and may be associated with reverse ventricular remodeling, reduced ejection&#xD;
      fraction (EF), left ventricular dilatation, functional mitral valve regurgitation, heart&#xD;
      failure and an increased rate of new onset atrial fibrillation.&#xD;
&#xD;
      Dependent on individual patient's characteristics, several strategies are established to&#xD;
      prevent and to overcome the potential drawbacks of chronic RVP. In general, unnecessary&#xD;
      ectopic RVP should be avoided. For example, in patients with sinus node disease and intact&#xD;
      atrioventricular (AV) conduction, atrial pacing, AV (search) hysteresis or AAI-DDD/ADI pacing&#xD;
      may be used. In patients with impaired cardiac function and an expected higher percentage of&#xD;
      RVP, pacing strategies for cardiac resynchronization are indicated. Conventional cardiac&#xD;
      resynchronization therapy (CRT) uses an additional transvenous left ventricular lead for&#xD;
      synchronous ventricular stimulation and was shown to shorten QRS duration and to reduce&#xD;
      morbidity and mortality in patients with chronic heart failure, left bundle branch block&#xD;
      (LBBB) and reduced EF. Due to the non-physiological left ventricular epicardial stimulation,&#xD;
      however, conventional CRT is associated with 30% of non-responders and may even prolong&#xD;
      ventricular activation in patients with narrower QRS complex. First described in 1968, His&#xD;
      bundle pacing (HBP) has evolved to an increasingly used alternative for cardiac pacing.&#xD;
      Currently, HBP is regarded the most physiologic approach for ventricular stimulation because&#xD;
      it prevents ventricular dyssynchrony and its potential fatal long-term consequences by&#xD;
      preserving normal electrical activation of the ventricles. Clinical benefit of HBP has been&#xD;
      shown compared with conventional permanent RVP and CRT. Recent studies documented restoration&#xD;
      of normal electrical and mechanical left ventricular synchrony for both selective and&#xD;
      non-selective HBP. However, compared with conventional RVP the implantation procedure for HBP&#xD;
      is much more demanding requiring exact placement of the pacing lead within the anatomically&#xD;
      variable His bundle area. Alternatively, the correction of bundle branch conduction disorders&#xD;
      has been demonstrated for left bundle branch area (LBBA) pacing. As a consequence, current&#xD;
      guidelines recommend pacing methods that maintain physiologic ventricular activation in&#xD;
      patients with atrioventricular block who have an indication for permanent pacing with a LVEF&#xD;
      between 36% and 50% and are expected to require ventricular pacing more than 40% of the time&#xD;
      (class IIa indication).&#xD;
&#xD;
      In summary, there is increasing evidence showing the benefits of the different strategies for&#xD;
      physiologic pacing but the appropriate use of these approaches may be challenging in the&#xD;
      individual case. Therefore, appropriate patient selection, implantation approaches, device&#xD;
      programming and follow-up require further intensive evaluation.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      Main goal of the study is to evaluate implantation success for pacing methods aiming to&#xD;
      maintain physiologic ventricular activation. Procedural success is defined as stable lead&#xD;
      positioning and effective pacing within the target area with an appropriate and stable pacing&#xD;
      threshold.&#xD;
&#xD;
      Secondary goals of the study are to document and to evaluate&#xD;
&#xD;
        -  procedural parameters (e.g. venous access, time needed for lead implant, procedural&#xD;
           duration, radiation) and adverse events dependent on procedural approaches and patients&#xD;
           characteristics,&#xD;
&#xD;
        -  performance of the implanted system (sensing, pacing thresholds) and clinical outcome&#xD;
           during routine follow-up&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      Single center, non-randomized, observational study, retrospective data analysis, on-going&#xD;
      prospective patient enrollment, descriptive statistics.&#xD;
&#xD;
      Center: Klinikum Fuerth (Dept. for Heart and Lung diseases, section for clinical&#xD;
      electrophysiology) / Germany in cooperation with the Dept. of Cardiology of the University&#xD;
      Erlangen / Germany and the University of Trieste / Italy.&#xD;
&#xD;
      Patients and methods:&#xD;
&#xD;
      Primary endpoint: Implantation success. Effective pacing and acceptable pacing threshold at&#xD;
      the targeted lead position. Target for lead placement is the area with maximum delayed&#xD;
      ventricular activation for transvenous CRT, the His bundle for selective or non-selective HBP&#xD;
      and the right interventricular septum with left bundle branch capture for LBBA pacing,&#xD;
      respectively. Target thresholds for the lead placed within the coronary sinus or at the&#xD;
      intrinsic conduction system is &lt;2.5 V @ 1 ms with a maximum acceptable threshold of &lt;4.0 V @&#xD;
      2 ms or &lt;5 V @ 1 ms. Target for all other leads is &lt;1 V @ 0.5 ms.&#xD;
&#xD;
      Secondary endpoints: patient characteristics and association with outcome. Implantation&#xD;
      success and outcome correlated with patient characteristics including electrocardiogram and&#xD;
      echocardiographic parameter and procedure related techniques and parameter. Safety: radiation&#xD;
      exposure, number and type of adverse events and adverse device related events. Follow-up:&#xD;
      device function, interrogation, programming and clinical outcome as evaluated in routine&#xD;
      follow-up, incl. ECG, echocardiography and parameter for assessment of heart failure.&#xD;
      Subpopulations: managed ventricular pacing, His bundle pacing, LBB-area pacing, CRT.&#xD;
      Implantation with or without electroanatomic mapping system.&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      Implantation of a pacemaker or ICD according to the current guidelines (Class I or IIa&#xD;
      indication) aiming to avoid pacing induced dyssynchrony, e.g. managed ventricular pacing,&#xD;
      His-bundle pacing, LBB-area pacing or conventional transvenous CRT. Age ≥ 18 years.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
      No given informed consent for the procedure. No follow up data available.&#xD;
&#xD;
      Sample size:&#xD;
&#xD;
      For the observational study, there is no pre-specified sample-size. Data from 200 patients&#xD;
      and procedures are expected.&#xD;
&#xD;
      Data security:&#xD;
&#xD;
      Study related data are collected by the study investigators in an anonymous clinic-internal&#xD;
      data-base that is password protected. All investigators have to provide valid GCP training.&#xD;
&#xD;
      Risk estimation:&#xD;
&#xD;
      The study is observational and descriptive with anonymized data collection and data analysis.&#xD;
      Therefore, the study adds no risk to the study population.&#xD;
&#xD;
      Ethics:&#xD;
&#xD;
      The &quot;Pace-Conduct&quot; study has been approved by the responsible ethics committee of the&#xD;
      Friedrich- Alexander University Erlangen, Germany (145_20 Bc)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">December 2030</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>CIED Implantation success</measure>
    <time_frame>peri-procedural</time_frame>
    <description>successful Pacemaker- or ICD implantation with effective pacing and acceptable pacing threshold in the targeted area</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pre-operative: Implantation related Patient characteristics</measure>
    <time_frame>1 month post implantation</time_frame>
    <description>association with procedural and post-implant outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intra-procedural: implant success related with procedural characteristics</measure>
    <time_frame>peri-procedural</time_frame>
    <description>correlation of Implantation success with Patient characteristics and procedural technical Parameter, eg. use of an electroanatomic mapping system</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>peri-procedural: safety and radiation</measure>
    <time_frame>peri-procedural</time_frame>
    <description>Radiation exposure and number and type of all adverse Events and adverse device associated events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>follow-up: device function</measure>
    <time_frame>one year</time_frame>
    <description>device parameter and programming during follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>follow-up: outcome</measure>
    <time_frame>one year</time_frame>
    <description>clinical Outcome during follow up</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Pacemaker DDD</condition>
  <condition>His Bundle Pacing</condition>
  <condition>LBB Area Pacing</condition>
  <condition>Pacing-Induced Cardiomyopathy</condition>
  <condition>Left Bundle-Branch Block</condition>
  <condition>ICD</condition>
  <arm_group>
    <arm_group_label>CIED for cardiac resynchronisation</arm_group_label>
    <description>Patients implanted with an CIED for cardiac resynchronisation aiming to avoid pacing induced ventricular dyssynchrony, e.g. His bundle pacing, LBB-area pacing, CRT. These different implanted types of devices may be further analysed as subgroups.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>cardiac implantable electronic device (CIED) implantation</intervention_name>
    <description>CIED Implantation according to the Guidelines aiming to avoid pacing induced dyssynchrony</description>
    <arm_group_label>CIED for cardiac resynchronisation</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing Pacemaker or ICD Implantation according to current Guidelines with the&#xD;
        aim to avoid pacing induced ventricular dyssynchrony.&#xD;
&#xD;
        Subgroups according to type of device implanted, lead Position and programming.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pacemaker or ICD Implantation aiming to avoid pacing induced ventricular dyssynchrony&#xD;
             according to current guidelines&#xD;
&#xD;
          -  age &gt;= 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no informed consent for the procedure given&#xD;
&#xD;
          -  no follow-up data&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dirk Bastian, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Klinikum-Fuerth</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dirk Bastian, MD</last_name>
    <phone>+49 911 7580 1101</phone>
    <email>dirk.bastian@klinikum-fuerth.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laura Vitali-Serdoz, MD</last_name>
    <phone>+49 911 7580 1101</phone>
    <email>laura.vitali-serdoz@klinikum-fuerth.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Klinikum Fuerth</name>
      <address>
        <city>Fuerth</city>
        <state>Bavaria</state>
        <zip>90766</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dirk Bastian, MD</last_name>
      <phone>+49 (0)911 7580 1101</phone>
      <email>dirk.bastian@klinikum-fuerth.de</email>
    </contact>
    <contact_backup>
      <last_name>Laura Vitali-Serdoz, MD</last_name>
      <phone>+49 (0)911 7580 1101</phone>
      <email>laura.vitali-serdoz@klinikum-fuerth.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 5, 2023</last_update_submitted>
  <last_update_submitted_qc>July 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>His bundle pacing</keyword>
  <keyword>LBB area pacing</keyword>
  <keyword>cardiac resynchronisation therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Bundle-Branch Block</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/NCT04416958
org study id: Pace_Cond_KHF
nct id: NCT04416958
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Right ventricular pacing causes ventricular dyssynchrony and may be associated with impaired
      outcome. In the last decade, several approaches for more physiological pacing became
      available and were implemented in the latest guidelines. However, compared to conventional
      device implantation, cardiac resynchronization, His bundle pacing and left bundle area pacing
      remain demanding procedures in the individual case. Goal of the single center observational
      "Pace conduct" study is to evaluate implantation success, safety and outcome of pacing
      methods that maintain physiologic ventricular activation.
Background:

      Conventional ectopic myocardial right ventricular pacing (RVP) causes ventricular
      dyssynchrony and may be associated with reverse ventricular remodeling, reduced ejection
      fraction (EF), left ventricular dilatation, functional mitral valve regurgitation, heart
      failure and an increased rate of new onset atrial fibrillation.

      Dependent on individual patient's characteristics, several strategies are established to
      prevent and to overcome the potential drawbacks of chronic RVP. In general, unnecessary
      ectopic RVP should be avoided. For example, in patients with sinus node disease and intact
      atrioventricular (AV) conduction, atrial pacing, AV (search) hysteresis or AAI-DDD/ADI pacing
      may be used. In patients with impaired cardiac function and an expected higher percentage of
      RVP, pacing strategies for cardiac resynchronization are indicated. Conventional cardiac
      resynchronization therapy (CRT) uses an additional transvenous left ventricular lead for
      synchronous ventricular stimulation and was shown to shorten QRS duration and to reduce
      morbidity and mortality in patients with chronic heart failure, left bundle branch block
      (LBBB) and reduced EF. Due to the non-physiological left ventricular epicardial stimulation,
      however, conventional CRT is associated with 30% of non-responders and may even prolong
      ventricular activation in patients with narrower QRS complex. First described in 1968, His
      bundle pacing (HBP) has evolved to an increasingly used alternative for cardiac pacing.
      Currently, HBP is regarded the most physiologic approach for ventricular stimulation because
      it prevents ventricular dyssynchrony and its potential fatal long-term consequences by
      preserving normal electrical activation of the ventricles. Clinical benefit of HBP has been
      shown compared with conventional permanent RVP and CRT. Recent studies documented restoration
      of normal electrical and mechanical left ventricular synchrony for both selective and
      non-selective HBP. However, compared with conventional RVP the implantation procedure for HBP
      is much more demanding requiring exact placement of the pacing lead within the anatomically
      variable His bundle area. Alternatively, the correction of bundle branch conduction disorders
      has been demonstrated for left bundle branch area (LBBA) pacing. As a consequence, current
      guidelines recommend pacing methods that maintain physiologic ventricular activation in
      patients with atrioventricular block who have an indication for permanent pacing with a LVEF
      between 36% and 50% and are expected to require ventricular pacing more than 40% of the time
      (class IIa indication).

      In summary, there is increasing evidence showing the benefits of the different strategies for
      physiologic pacing but the appropriate use of these approaches may be challenging in the
      individual case. Therefore, appropriate patient selection, implantation approaches, device
      programming and follow-up require further intensive evaluation.

      Objective:

      Main goal of the study is to evaluate implantation success for pacing methods aiming to
      maintain physiologic ventricular activation. Procedural success is defined as stable lead
      positioning and effective pacing within the target area with an appropriate and stable pacing
      threshold.

      Secondary goals of the study are to document and to evaluate

        -  procedural parameters (e.g. venous access, time needed for lead implant, procedural
           duration, radiation) and adverse events dependent on procedural approaches and patients
           characteristics,

        -  performance of the implanted system (sensing, pacing thresholds) and clinical outcome
           during routine follow-up

      Study design:

      Single center, non-randomized, observational study, retrospective data analysis, on-going
      prospective patient enrollment, descriptive statistics.

      Center: Klinikum Fuerth (Dept. for Heart and Lung diseases, section for clinical
      electrophysiology) / Germany in cooperation with the Dept. of Cardiology of the University
      Erlangen / Germany and the University of Trieste / Italy.

      Patients and methods:

      Primary endpoint: Implantation success. Effective pacing and acceptable pacing threshold at
      the targeted lead position. Target for lead placement is the area with maximum delayed
      ventricular activation for transvenous CRT, the His bundle for selective or non-selective HBP
      and the right interventricular septum with left bundle branch capture for LBBA pacing,
      respectively. Target thresholds for the lead placed within the coronary sinus or at the
      intrinsic conduction system is <2.5 V @ 1 ms with a maximum acceptable threshold of <4.0 V @
      2 ms or <5 V @ 1 ms. Target for all other leads is <1 V @ 0.5 ms.

      Secondary endpoints: patient characteristics and association with outcome. Implantation
      success and outcome correlated with patient characteristics including electrocardiogram and
      echocardiographic parameter and procedure related techniques and parameter. Safety: radiation
      exposure, number and type of adverse events and adverse device related events. Follow-up:
      device function, interrogation, programming and clinical outcome as evaluated in routine
      follow-up, incl. ECG, echocardiography and parameter for assessment of heart failure.
      Subpopulations: managed ventricular pacing, His bundle pacing, LBB-area pacing, CRT.
      Implantation with or without electroanatomic mapping system.

      Inclusion criteria:

      Implantation of a pacemaker or ICD according to the current guidelines (Class I or IIa
      indication) aiming to avoid pacing induced dyssynchrony, e.g. managed ventricular pacing,
      His-bundle pacing, LBB-area pacing or conventional transvenous CRT. Age ≥ 18 years.

      Exclusion criteria:

      No given informed consent for the procedure. No follow up data available.

      Sample size:

      For the observational study, there is no pre-specified sample-size. Data from 200 patients
      and procedures are expected.

      Data security:

      Study related data are collected by the study investigators in an anonymous clinic-internal
      data-base that is password protected. All investigators have to provide valid GCP training.

      Risk estimation:

      The study is observational and descriptive with anonymized data collection and data analysis.
      Therefore, the study adds no risk to the study population.

      Ethics:

      The "Pace-Conduct" study has been approved by the responsible ethics committee of the
      Friedrich- Alexander University Erlangen, Germany (145_20 Bc)
observational model: Cohort
time perspective: Prospective
measure: CIED Implantation success
time frame: peri-procedural
description: successful Pacemaker- or ICD implantation with effective pacing and acceptable pacing threshold in the targeted area
measure: pre-operative: Implantation related Patient characteristics
time frame: 1 month post implantation
description: association with procedural and post-implant outcome
measure: intra-procedural: implant success related with procedural characteristics
time frame: peri-procedural
description: correlation of Implantation success with Patient characteristics and procedural technical Parameter, eg. use of an electroanatomic mapping system
measure: peri-procedural: safety and radiation
time frame: peri-procedural
description: Radiation exposure and number and type of all adverse Events and adverse device associated events
measure: follow-up: device function
time frame: one year
description: device parameter and programming during follow up
measure: follow-up: outcome
time frame: one year
description: clinical Outcome during follow up
arm group label: CIED for cardiac resynchronisation
description: Patients implanted with an CIED for cardiac resynchronisation aiming to avoid pacing induced ventricular dyssynchrony, e.g. His bundle pacing, LBB-area pacing, CRT. These different implanted types of devices may be further analysed as subgroups.
intervention type: Device
intervention name: cardiac implantable electronic device (CIED) implantation
description: CIED Implantation according to the Guidelines aiming to avoid pacing induced dyssynchrony
arm group label: CIED for cardiac resynchronisation
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dirk Bastian, MD
role: Principal Investigator
affiliation: Klinikum-Fuerth
last name: Dirk Bastian, MD
phone: +49 911 7580 1101
email: dirk.bastian@klinikum-fuerth.de
last name: Laura Vitali-Serdoz, MD
phone: +49 911 7580 1101
email: laura.vitali-serdoz@klinikum-fuerth.de
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Bundle-Branch Block
sharing ipd: No