<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/NCT03024047</url>
  </required_header>
  <id_info>
    <org_study_id>DAN-BLOCK_Study1</org_study_id>
    <nct_id>NCT03024047</nct_id>
  </id_info>
  <brief_title>Cohort Description of Younger With AV-block</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Disturbances of the heart's atrioventricular conduction - AV-block - may show by shortness of&#xD;
      breath, fainting or sudden death. If AV-block is diagnosed in time pacemaker therapy may be&#xD;
      lifesaving.&#xD;
&#xD;
      AV-block in younger can be seen along with structural or ischemic heart disease, congenital&#xD;
      heart disease (incl. congenital AV-block) storage disorders, specific muscle diseases,&#xD;
      sarcoidosis, Borrelia infection or drug intoxication. AV-block in younger can also be seen in&#xD;
      conditions, primarily localized to the AV-node without other cardiac disease at diagnosis.&#xD;
&#xD;
      This form of AV-block is often hereditary and can be seen in families where relatives have&#xD;
      another types of heart disease in form of fore example, cardiomyopathy, ion channel disease&#xD;
      or sudden death. The different forms of presentation are due to the same gene mutation being&#xD;
      expressed differently within the same family. Thus, early onset of AV-block (&lt;50 years) may&#xD;
      indicate hereditary AV-conduction disorder but it can also be the first manifestation of&#xD;
      severe ion channel disease or cardiomyopathy.&#xD;
&#xD;
      Denmark has annually over 50 individuals &lt;50 years treated with pacemaker due to advanced&#xD;
      AV-block. There have been no overall figures regarding the causes of advanced AV-block, and&#xD;
      therefore no systematic approach to diagnosing this group of patients. Furthermore, the&#xD;
      prevalence of individuals with a genetic cause of AV-block is unknown and presumably an often&#xD;
      overlooked diagnosis among younger patients with advanced AV-blok. There are no data on&#xD;
      disease progression after diagnosis, and therefore there is no evidence-based knowledge about&#xD;
      how these patients should be followed after diagnosis.&#xD;
&#xD;
      With modern gene technology, a range of new, yet unknown genes with potentially pathogenic&#xD;
      mutations is likely to be identified. Identification of such genes, and the development of a&#xD;
      strategy for systematic approach to diagnose younger patients with AV-block, will enable&#xD;
      presymptomatic genetic screening of relatives and implementation of evidence-based,&#xD;
      preventive treatment with pacemaker and/or medical treatment for heart failure based on a&#xD;
      specific genetic predisposition for development of AV-block with or without heart failure.&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      In a significant proportion of younger patients with advanced AV-block the underlying cause&#xD;
      is unknown.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To investigate the prevalence and causes of advanced AV-block in younger patients in Denmark&#xD;
      and describe the current diagnostics.&#xD;
&#xD;
      Method:&#xD;
&#xD;
      The study is a cross sectional study. The patients for this study are identified from Danish&#xD;
      Pacemaker and ICD Register. The investigators will review medical records and obtain clinical&#xD;
      information and test results (see detailed description).&#xD;
&#xD;
      Perspectives:&#xD;
&#xD;
      This study is the first part of a large study of AV-block in younger patients in Denmark. The&#xD;
      overall goal, is to increase knowledge about the causes of and disease progression after the&#xD;
      diagnosis of advanced AV-block in young patients which could lead to a significant&#xD;
      improvement in the treatment of this patient group and may lead to a customized choice of&#xD;
      pacemaker type in the future and perhaps additional medical treatment in this patient group.&#xD;
      This could potentially lead to a reduction in both their morbidity mortality.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Method:&#xD;
&#xD;
      The following covariates will be reported.&#xD;
&#xD;
      Date of diagnosis of AV-block:&#xD;
&#xD;
      The date of diagnosis is defined as the day the physician diagnoses the AV-block. E.g. if the&#xD;
      patient has a Holter monitoring performed, the date of diagnosis is the dag the monitoring is&#xD;
      reviewed.&#xD;
&#xD;
      Reported as: Day-month-year&#xD;
&#xD;
      Comorbidity at day of first pacemaker implant:&#xD;
&#xD;
      Registered as one or more of the following:&#xD;
&#xD;
        1. Diabetes&#xD;
&#xD;
        2. Hypertension&#xD;
&#xD;
        3. Hypercholesterolemia&#xD;
&#xD;
        4. Heart failure&#xD;
&#xD;
        5. Atrial fibrillation or flutter&#xD;
&#xD;
        6. Ischemic heart disease&#xD;
&#xD;
        7. Sarcoidosis&#xD;
&#xD;
        8. Connecting tissue disorder&#xD;
&#xD;
        9. Other&#xD;
&#xD;
      Smoking status at day of first pacemaker implant:&#xD;
&#xD;
      Registered as: Current, former, never&#xD;
&#xD;
      Device selected at first pacemaker implant:&#xD;
&#xD;
      Registered as: DDD, CTR, etcetera&#xD;
&#xD;
      Genetic investigation:&#xD;
&#xD;
      Is there performed genetic investigation due to the finding of AV-block? Investigation must&#xD;
      be initiated maximum 4 weeks after day of first pacemaker implant.&#xD;
&#xD;
      Registered as: y/n.&#xD;
&#xD;
      Date of first pacemaker implant:&#xD;
&#xD;
      Registered as: Day-month-year&#xD;
&#xD;
      Implant sight&#xD;
&#xD;
      ECG 12 description:&#xD;
&#xD;
      ECG 12 must be taken maximum one week before day of first pacemaker implant Registered as:&#xD;
      Bpm., RBBB y/n, LBBB y/n, PR in msec, QRS in msec, QT in msec, QTc in msec (Frederica)&#xD;
&#xD;
      Implant indication:&#xD;
&#xD;
      Registered as one of following:&#xD;
&#xD;
        1. First-degree atrioventricular block with symptoms&#xD;
&#xD;
        2. Mobitz type 1 with symptoms&#xD;
&#xD;
        3. Mobitz type 2&#xD;
&#xD;
        4. Advanced second-degree atrioventricular block&#xD;
&#xD;
        5. Third-degree atrioventricular block&#xD;
&#xD;
        6. Unknown The most malignant is chosen and it is reported if it is intermittent or&#xD;
           persistent.&#xD;
&#xD;
      Symptoms:&#xD;
&#xD;
      Registered as one or more of following:&#xD;
&#xD;
        1. Dyspnoea&#xD;
&#xD;
        2. Fatigue&#xD;
&#xD;
        3. Malaise&#xD;
&#xD;
        4. Dizziness&#xD;
&#xD;
        5. Syncope&#xD;
&#xD;
        6. Angina&#xD;
&#xD;
        7. Cardiac arrest&#xD;
&#xD;
        8. No symptoms&#xD;
&#xD;
      Echocardiography:&#xD;
&#xD;
      Performed maximum two weeks before day of first pacemaker implant The reported values are&#xD;
      what the echocardiographer describes.&#xD;
&#xD;
      Registered as:&#xD;
&#xD;
      LVEF in % (values over 60% is reported as &gt;60 %) Hypertrophy of LV y/n Dilatation of LV y/n&#xD;
      Dilatation of LA y/n Valvular disease/artificial valve y/n&#xD;
&#xD;
      Coronary angiography:&#xD;
&#xD;
      At day of first pacemaker implant +/- 4 weeks&#xD;
&#xD;
      Registered as:&#xD;
&#xD;
      Normal y/n Significantly disease on LAD y/n Significantly disease on RCA y/n Significantly&#xD;
      disease on CX y/n Significantly disease = leading to CABG, PCI or antithrombotic treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <primary_completion_date type="Anticipated">August 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prevalence of structural heart disease as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of ischemic heart disease as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of congenital heart disease as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of congenital AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of muscular dystrophy as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of sarcoidosis as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of lyme disease as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of genetic cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of complications to operation as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of complications to radio frequency ablation as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of endocarditis as cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of unknown cause of AV-block</measure>
    <time_frame>01.01.1996 - 31.12.2015</time_frame>
  </primary_outcome>
  <enrollment type="Anticipated">1255</enrollment>
  <condition>Atrioventricular Block</condition>
  <condition>Progressive Cardiac Conduction Defect</condition>
  <condition>Genetic Disease</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Pacemaker</intervention_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All patients in Denmark with AV-block who were treated with pacemaker for the first time&#xD;
        between 01.01.1996 - 31.12.2015 with age at implantation &lt;50 years will be included in the&#xD;
        study (n=1,255 patients).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients in Denmark&#xD;
&#xD;
          -  Treated with pacemaker due to AV-block&#xD;
&#xD;
          -  Implanted for the first time between 01.01.1996 - 31.12.2015&#xD;
&#xD;
          -  Age at implantation &lt;50 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Johnni T. R. Dideriksen, M.D.</last_name>
    <phone>0045 40832508</phone>
    <email>johndide@rm.dk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of cardiology, Research, Aarhus University Hospital, Denmark</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <contact>
      <last_name>Johnni T. R. Dideriksen, M.D.</last_name>
      <phone>0045 40832508</phone>
      <email>johndide@rm.dk</email>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>January 13, 2017</last_update_submitted>
  <last_update_submitted_qc>January 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 18, 2017</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>Atrioventricular Block</mesh_term>
    <mesh_term>Cardiac Conduction System Disease</mesh_term>
    <mesh_term>Bundle-Branch Block</mesh_term>
    <mesh_term>Genetic Diseases, Inborn</mesh_term>
  </condition_browse>
  <!-- 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/NCT03024047
org study id: DAN-BLOCK_Study1
nct id: NCT03024047
lead sponsor: 
has dmc: Yes
Background:

      Disturbances of the heart's atrioventricular conduction - AV-block - may show by shortness of
      breath, fainting or sudden death. If AV-block is diagnosed in time pacemaker therapy may be
      lifesaving.

      AV-block in younger can be seen along with structural or ischemic heart disease, congenital
      heart disease (incl. congenital AV-block) storage disorders, specific muscle diseases,
      sarcoidosis, Borrelia infection or drug intoxication. AV-block in younger can also be seen in
      conditions, primarily localized to the AV-node without other cardiac disease at diagnosis.

      This form of AV-block is often hereditary and can be seen in families where relatives have
      another types of heart disease in form of fore example, cardiomyopathy, ion channel disease
      or sudden death. The different forms of presentation are due to the same gene mutation being
      expressed differently within the same family. Thus, early onset of AV-block (<50 years) may
      indicate hereditary AV-conduction disorder but it can also be the first manifestation of
      severe ion channel disease or cardiomyopathy.

      Denmark has annually over 50 individuals <50 years treated with pacemaker due to advanced
      AV-block. There have been no overall figures regarding the causes of advanced AV-block, and
      therefore no systematic approach to diagnosing this group of patients. Furthermore, the
      prevalence of individuals with a genetic cause of AV-block is unknown and presumably an often
      overlooked diagnosis among younger patients with advanced AV-blok. There are no data on
      disease progression after diagnosis, and therefore there is no evidence-based knowledge about
      how these patients should be followed after diagnosis.

      With modern gene technology, a range of new, yet unknown genes with potentially pathogenic
      mutations is likely to be identified. Identification of such genes, and the development of a
      strategy for systematic approach to diagnose younger patients with AV-block, will enable
      presymptomatic genetic screening of relatives and implementation of evidence-based,
      preventive treatment with pacemaker and/or medical treatment for heart failure based on a
      specific genetic predisposition for development of AV-block with or without heart failure.

      Hypotheses:

      In a significant proportion of younger patients with advanced AV-block the underlying cause
      is unknown.

      Objective:

      To investigate the prevalence and causes of advanced AV-block in younger patients in Denmark
      and describe the current diagnostics.

      Method:

      The study is a cross sectional study. The patients for this study are identified from Danish
      Pacemaker and ICD Register. The investigators will review medical records and obtain clinical
      information and test results (see detailed description).

      Perspectives:

      This study is the first part of a large study of AV-block in younger patients in Denmark. The
      overall goal, is to increase knowledge about the causes of and disease progression after the
      diagnosis of advanced AV-block in young patients which could lead to a significant
      improvement in the treatment of this patient group and may lead to a customized choice of
      pacemaker type in the future and perhaps additional medical treatment in this patient group.
      This could potentially lead to a reduction in both their morbidity mortality.
Method:

      The following covariates will be reported.

      Date of diagnosis of AV-block:

      The date of diagnosis is defined as the day the physician diagnoses the AV-block. E.g. if the
      patient has a Holter monitoring performed, the date of diagnosis is the dag the monitoring is
      reviewed.

      Reported as: Day-month-year

      Comorbidity at day of first pacemaker implant:

      Registered as one or more of the following:

        1. Diabetes

        2. Hypertension

        3. Hypercholesterolemia

        4. Heart failure

        5. Atrial fibrillation or flutter

        6. Ischemic heart disease

        7. Sarcoidosis

        8. Connecting tissue disorder

        9. Other

      Smoking status at day of first pacemaker implant:

      Registered as: Current, former, never

      Device selected at first pacemaker implant:

      Registered as: DDD, CTR, etcetera

      Genetic investigation:

      Is there performed genetic investigation due to the finding of AV-block? Investigation must
      be initiated maximum 4 weeks after day of first pacemaker implant.

      Registered as: y/n.

      Date of first pacemaker implant:

      Registered as: Day-month-year

      Implant sight

      ECG 12 description:

      ECG 12 must be taken maximum one week before day of first pacemaker implant Registered as:
      Bpm., RBBB y/n, LBBB y/n, PR in msec, QRS in msec, QT in msec, QTc in msec (Frederica)

      Implant indication:

      Registered as one of following:

        1. First-degree atrioventricular block with symptoms

        2. Mobitz type 1 with symptoms

        3. Mobitz type 2

        4. Advanced second-degree atrioventricular block

        5. Third-degree atrioventricular block

        6. Unknown The most malignant is chosen and it is reported if it is intermittent or
           persistent.

      Symptoms:

      Registered as one or more of following:

        1. Dyspnoea

        2. Fatigue

        3. Malaise

        4. Dizziness

        5. Syncope

        6. Angina

        7. Cardiac arrest

        8. No symptoms

      Echocardiography:

      Performed maximum two weeks before day of first pacemaker implant The reported values are
      what the echocardiographer describes.

      Registered as:

      LVEF in % (values over 60% is reported as >60 %) Hypertrophy of LV y/n Dilatation of LV y/n
      Dilatation of LA y/n Valvular disease/artificial valve y/n

      Coronary angiography:

      At day of first pacemaker implant +/- 4 weeks

      Registered as:

      Normal y/n Significantly disease on LAD y/n Significantly disease on RCA y/n Significantly
      disease on CX y/n Significantly disease = leading to CABG, PCI or antithrombotic treatment
time perspective: Retrospective
measure: Prevalence of structural heart disease as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of ischemic heart disease as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of congenital heart disease as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of congenital AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of muscular dystrophy as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of sarcoidosis as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of lyme disease as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of genetic cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of complications to operation as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of complications to radio frequency ablation as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of endocarditis as cause of AV-block
time frame: 01.01.1996 - 31.12.2015
measure: Prevalence of unknown cause of AV-block
time frame: 01.01.1996 - 31.12.2015
intervention type: Device
intervention name: Pacemaker
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 49 Years
healthy volunteers: No
last name: Johnni T. R. Dideriksen, M.D.
phone: 0045 40832508
email: johndide@rm.dk
facility: 
contact: 
country: Denmark
responsible party type: Sponsor
mesh term: Atrioventricular Block
mesh term: Cardiac Conduction System Disease
mesh term: Bundle-Branch Block
mesh term: Genetic Diseases, Inborn