<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/NCT03801681</url>
  </required_header>
  <id_info>
    <org_study_id>ARMY</org_study_id>
    <nct_id>NCT03801681</nct_id>
  </id_info>
  <brief_title>ARrhythmias in MYocarditis</brief_title>
  <acronym>ARMY</acronym>
  <official_title>Risk Assessment of Cardiac ARrhythmias in Patients With MYocarditis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Warsaw</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>
      Myocarditis promotes the occurrence of serious cardiac arrhythmias and conduction disorders&#xD;
      which may lead to sudden cardiac death, the need for catheter ablation of arrhythmia or&#xD;
      implantation of a cardioverter-defibrillator or pacemaker. The aim of the study is to fill&#xD;
      the evidence gap regarding the type and burden of arrhythmias in patients with myocarditis&#xD;
      and their correlation with clinical parameters, biomarkers and additional tests. During a&#xD;
      multi-center observational study, patients will be subjected to prolonged ECG monitoring. As&#xD;
      a result, a risk scale will be created that can facilitate the identification of patients&#xD;
      with an increased risk of arrhythmia and further specifying recommendations for therapeutic&#xD;
      management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Myocarditis is a serious social problem, usually affecting young or middle-aged people.&#xD;
      Making of the diagnosis of myocarditis, due to the varied course of the disease, is a&#xD;
      significant challenge, therefore clinical suspicion of myocarditis is based on symptoms and&#xD;
      abnormalities in additional tests (ECG, echocardiography, magnetic resonance of the heart,&#xD;
      biomarkers), which should be confirmed by cardiac biopsy. Despite the fact that in the&#xD;
      majority of patients myocarditis occurs in a mild and uncomplicated manner, in some patients&#xD;
      the inflammatory process progresses leading to dilated cardiomyopathy, end-stage heart&#xD;
      failure and often to the need for heart transplantation. Myocarditis also promotes the&#xD;
      occurrence of severe arrhythmias and conduction which may lead to sudden cardiac death&#xD;
      (myocarditis is confirmed in autopsy even in 2-42% of cases), the need for percutaneous&#xD;
      ablation of arrhythmia, cardioverter-defibrillator implantation or cardiac stimulator.&#xD;
&#xD;
      In order to better identify the causes and improve the diagnosis and treatment of&#xD;
      myocarditis, new data are needed including biomarkers (including biochemical, genetic,&#xD;
      immunohistochemical biomarkers) responsible for the process of necrosis, fibrosis,&#xD;
      haemodynamic stress of myocardium in the course of myocarditis, as well as studies aimed at&#xD;
      identifying pathogens that cause myocarditis and factors predisposing to the onset of&#xD;
      myocarditis. In addition, there is no systematic information on the type and burden of&#xD;
      arrhythmias and their variability over time. A significant deficiency of research in the&#xD;
      field of the above biomarkers and the severity of arrhythmia in the course of myocarditis&#xD;
      translates into the lack of clear recommendations on the myocarditis management from the&#xD;
      scientific societies and often leads to wrong therapeutic decisions.&#xD;
&#xD;
      The aim of the study is to fill the evidence gap regarding the diagnostic and prognostic&#xD;
      value of biomarkers, as well as the type and burden of arrhythmias in patients with&#xD;
      myocarditis.&#xD;
&#xD;
      This will be a non-interventional, observational study. The study will include 100 adult&#xD;
      patients with confirmed (based on clinical findings, in accordance with applicable&#xD;
      guidelines) first myocarditis episode, who agree to participate in the study.&#xD;
&#xD;
      During the multicenter observational study will be collected basic demographic data, current&#xD;
      diagnosis, current disease history and clinical presentation of symptoms, laboratory tests&#xD;
      results and all other additional tests carried out during or after index hospitalization.&#xD;
      During the index hospitalization peripheral venous blood (10 ml) will be collected to obtain&#xD;
      serum for further diagnostic tests (i.e. biochemical, genetic). The obtained material will be&#xD;
      stored frozen until analysis. The tested biomarkers will include those that have a confirmed&#xD;
      role in the diagnosis of myocardial necrosis, in inflammatory processes and fibrosis of the&#xD;
      myocardium, participate in the pathophysiology of arrhythmia and heart failure development,&#xD;
      i.e. high sensitive troponin, N-terminal-pro Brain Natriuretic Peptide (NT-proBNP),&#xD;
      Galectin-3, (Suppression of Tumorigenicity 2) ST2.&#xD;
&#xD;
      Additionally, in selected cases, when a biopsy of the heart is performed in the course of the&#xD;
      independent diagnostic procedure, the heart muscle biopsies will be analyzed. In the&#xD;
      collected material (both in blood and biopsy samples) immunohistochemistry, virology and&#xD;
      genetic research will be performed for specific antibodies and genetic material of pathogens&#xD;
      causing myocarditis (mainly viruses, i.e. parvovirus B19, coxsackie, adenovirus).&#xD;
&#xD;
      The immunogenetic predisposition, as well as gene profiling of people who have become ill&#xD;
      with myocarditis will also be sought.&#xD;
&#xD;
      In addition, patients will undergo prolonged ECG Holter monitoring for up to 7 days from the&#xD;
      moment of consenting to participate in the study. Registered ECG recordings will be evaluated&#xD;
      after the completed follow-up period. Then, after 3-months form inclusion in the study, a&#xD;
      control visit will be made assessing the clinical condition of patients, clinical&#xD;
      examination, collection of blood samples, standard resting 12-lead ECG, and 7-day ECG-Holter&#xD;
      monitoring. Other study endpoints will be assessed after 1-year observation. The next stage&#xD;
      will be the analysis of clinical history, obtained results of ECG monitoring, biomarkers and&#xD;
      additional tests.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</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>Assessment of type and burden of arrhythmia using Holter-ECG monitoring in patients with myocarditis.</measure>
    <time_frame>3 months</time_frame>
    <description>During the Holter-ECG monitoring type and burden of arrhythmias or cardiac rhythm disorders will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to occurrence of new heart failure, heart failure hospitalizations or heart failure outpatient visits.</measure>
    <time_frame>1 year</time_frame>
    <description>it will be assessed on clinical interview during control visits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to occurrence of cardiovascular hospitalization.</measure>
    <time_frame>1 year</time_frame>
    <description>it will be assessed on clinical interview during control visits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to occurrence to left ventricular systolic dysfunction.</measure>
    <time_frame>1 year</time_frame>
    <description>left ventricular systolic dysfunction occurrence will be assessed using echocardiography during control visits.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to occurrence to left ventricular diastolic dysfunction.</measure>
    <time_frame>1 year</time_frame>
    <description>left ventricular diastolic dysfunction occurrence will be assessed using echocardiography during control visits.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation of serum biomarkers concentrations with cardiac remodeling</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of serum biomarkers concentrations with inflammation</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Myocarditis</condition>
  <condition>Heart Failure</condition>
  <condition>Endomyocardial Biopsy</condition>
  <condition>Arrythmia</condition>
  <condition>Sudden Cardiac Death</condition>
  <condition>Biomarker</condition>
  <condition>Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>myocarditis</arm_group_label>
    <description>patients with clinically suspected myocarditis</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>ECG holter monitoring</intervention_name>
    <description>patients will be monitored using ECG-holter</description>
    <arm_group_label>myocarditis</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients admitted to the hospital having clinically suspected myocarditis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  clinically suspected myocarditis&#xD;
&#xD;
          -  age ≥ 18 years&#xD;
&#xD;
          -  signed informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous history of heart failure&#xD;
&#xD;
          -  already Implanted implantable cardioverter-defibrillator (ICD), cardiac&#xD;
             resynchronization therapy (CRT) or pacemaker (PM)&#xD;
&#xD;
          -  history of percutaneous ablation due to arrhythmias&#xD;
&#xD;
          -  history of arrhythmias or conduction disorders&#xD;
&#xD;
          -  active cancer&#xD;
&#xD;
          -  advanced chronic kidney disease&#xD;
&#xD;
          -  chronic inflammatory disease&#xD;
&#xD;
          -  previous or current myocardial infarction&#xD;
&#xD;
          -  current myocardial ischemia as the cause of arrhythmia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Grzegorz Opolski, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Medical University of Warsaw</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Krzysztof J Filipiak, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Medical University of Warsaw</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Krzysztof Ozierański, MD</last_name>
    <phone>22 5991958</phone>
    <phone_ext>+48</phone_ext>
    <email>krzysztof.ozieranski@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Agata Tymińska, MD</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>1st Chair and Department of Cardiology, Medical University of Warsaw</name>
      <address>
        <city>Warsaw</city>
        <zip>02-097</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Krzysztof Ozierański, MD</last_name>
      <email>krzysztof.ozieranski@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Krzysztof Ozierański, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Agata Tymińska, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jerzy Kłoszewski, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maciej Kusztal, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 5, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>January 10, 2019</last_update_submitted>
  <last_update_submitted_qc>January 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Warsaw</investigator_affiliation>
    <investigator_full_name>Krzysztof Ozieranski</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>myocarditis</keyword>
  <keyword>heart failure</keyword>
  <keyword>endomyocardial biopsy</keyword>
  <keyword>arrythmia</keyword>
  <keyword>sudden cardiac death</keyword>
  <keyword>biomarker</keyword>
  <keyword>cardiomyopathy</keyword>
  <keyword>high-sensitive troponin</keyword>
  <keyword>galectin-3</keyword>
  <keyword>st-2</keyword>
  <keyword>NT-proBNP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Arrhythmias, Cardiac</mesh_term>
    <mesh_term>Death, Sudden, Cardiac</mesh_term>
    <mesh_term>Myocarditis</mesh_term>
    <mesh_term>Death</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>after contact</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_access_criteria>principal investigator approval</ipd_access_criteria>
  </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/NCT03801681
org study id: ARMY
nct id: NCT03801681
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Myocarditis promotes the occurrence of serious cardiac arrhythmias and conduction disorders
      which may lead to sudden cardiac death, the need for catheter ablation of arrhythmia or
      implantation of a cardioverter-defibrillator or pacemaker. The aim of the study is to fill
      the evidence gap regarding the type and burden of arrhythmias in patients with myocarditis
      and their correlation with clinical parameters, biomarkers and additional tests. During a
      multi-center observational study, patients will be subjected to prolonged ECG monitoring. As
      a result, a risk scale will be created that can facilitate the identification of patients
      with an increased risk of arrhythmia and further specifying recommendations for therapeutic
      management.
Myocarditis is a serious social problem, usually affecting young or middle-aged people.
      Making of the diagnosis of myocarditis, due to the varied course of the disease, is a
      significant challenge, therefore clinical suspicion of myocarditis is based on symptoms and
      abnormalities in additional tests (ECG, echocardiography, magnetic resonance of the heart,
      biomarkers), which should be confirmed by cardiac biopsy. Despite the fact that in the
      majority of patients myocarditis occurs in a mild and uncomplicated manner, in some patients
      the inflammatory process progresses leading to dilated cardiomyopathy, end-stage heart
      failure and often to the need for heart transplantation. Myocarditis also promotes the
      occurrence of severe arrhythmias and conduction which may lead to sudden cardiac death
      (myocarditis is confirmed in autopsy even in 2-42% of cases), the need for percutaneous
      ablation of arrhythmia, cardioverter-defibrillator implantation or cardiac stimulator.

      In order to better identify the causes and improve the diagnosis and treatment of
      myocarditis, new data are needed including biomarkers (including biochemical, genetic,
      immunohistochemical biomarkers) responsible for the process of necrosis, fibrosis,
      haemodynamic stress of myocardium in the course of myocarditis, as well as studies aimed at
      identifying pathogens that cause myocarditis and factors predisposing to the onset of
      myocarditis. In addition, there is no systematic information on the type and burden of
      arrhythmias and their variability over time. A significant deficiency of research in the
      field of the above biomarkers and the severity of arrhythmia in the course of myocarditis
      translates into the lack of clear recommendations on the myocarditis management from the
      scientific societies and often leads to wrong therapeutic decisions.

      The aim of the study is to fill the evidence gap regarding the diagnostic and prognostic
      value of biomarkers, as well as the type and burden of arrhythmias in patients with
      myocarditis.

      This will be a non-interventional, observational study. The study will include 100 adult
      patients with confirmed (based on clinical findings, in accordance with applicable
      guidelines) first myocarditis episode, who agree to participate in the study.

      During the multicenter observational study will be collected basic demographic data, current
      diagnosis, current disease history and clinical presentation of symptoms, laboratory tests
      results and all other additional tests carried out during or after index hospitalization.
      During the index hospitalization peripheral venous blood (10 ml) will be collected to obtain
      serum for further diagnostic tests (i.e. biochemical, genetic). The obtained material will be
      stored frozen until analysis. The tested biomarkers will include those that have a confirmed
      role in the diagnosis of myocardial necrosis, in inflammatory processes and fibrosis of the
      myocardium, participate in the pathophysiology of arrhythmia and heart failure development,
      i.e. high sensitive troponin, N-terminal-pro Brain Natriuretic Peptide (NT-proBNP),
      Galectin-3, (Suppression of Tumorigenicity 2) ST2.

      Additionally, in selected cases, when a biopsy of the heart is performed in the course of the
      independent diagnostic procedure, the heart muscle biopsies will be analyzed. In the
      collected material (both in blood and biopsy samples) immunohistochemistry, virology and
      genetic research will be performed for specific antibodies and genetic material of pathogens
      causing myocarditis (mainly viruses, i.e. parvovirus B19, coxsackie, adenovirus).

      The immunogenetic predisposition, as well as gene profiling of people who have become ill
      with myocarditis will also be sought.

      In addition, patients will undergo prolonged ECG Holter monitoring for up to 7 days from the
      moment of consenting to participate in the study. Registered ECG recordings will be evaluated
      after the completed follow-up period. Then, after 3-months form inclusion in the study, a
      control visit will be made assessing the clinical condition of patients, clinical
      examination, collection of blood samples, standard resting 12-lead ECG, and 7-day ECG-Holter
      monitoring. Other study endpoints will be assessed after 1-year observation. The next stage
      will be the analysis of clinical history, obtained results of ECG monitoring, biomarkers and
      additional tests.
observational model: Cohort
time perspective: Prospective
measure: Assessment of type and burden of arrhythmia using Holter-ECG monitoring in patients with myocarditis.
time frame: 3 months
description: During the Holter-ECG monitoring type and burden of arrhythmias or cardiac rhythm disorders will be assessed.
measure: Time to occurrence of new heart failure, heart failure hospitalizations or heart failure outpatient visits.
time frame: 1 year
description: it will be assessed on clinical interview during control visits
measure: Time to occurrence of cardiovascular hospitalization.
time frame: 1 year
description: it will be assessed on clinical interview during control visits
measure: Time to occurrence to left ventricular systolic dysfunction.
time frame: 1 year
description: left ventricular systolic dysfunction occurrence will be assessed using echocardiography during control visits.
measure: Time to occurrence to left ventricular diastolic dysfunction.
time frame: 1 year
description: left ventricular diastolic dysfunction occurrence will be assessed using echocardiography during control visits.
measure: Correlation of serum biomarkers concentrations with cardiac remodeling
time frame: 1 year
measure: Correlation of serum biomarkers concentrations with inflammation
time frame: 1 year
arm group label: myocarditis
description: patients with clinically suspected myocarditis
intervention type: Diagnostic Test
intervention name: ECG holter monitoring
description: patients will be monitored using ECG-holter
arm group label: myocarditis
blood samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Grzegorz Opolski, Professor
role: Study Chair
affiliation: Medical University of Warsaw
last name: Krzysztof J Filipiak, Professor
role: Study Chair
affiliation: Medical University of Warsaw
last name: Krzysztof Ozierański, MD
phone: 22 5991958
phone ext: +48
email: krzysztof.ozieranski@gmail.com
last name: Agata Tymińska, MD
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Medical University of Warsaw
investigator full name: Krzysztof Ozieranski
investigator title: Principal Investigator
mesh term: Heart Failure
mesh term: Cardiomyopathies
mesh term: Arrhythmias, Cardiac
mesh term: Death, Sudden, Cardiac
mesh term: Myocarditis
mesh term: Death
sharing ipd: Yes
ipd description: after contact
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd access criteria: principal investigator approval