<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/NCT04499612</url>
  </required_header>
  <id_info>
    <org_study_id>05/290120</org_study_id>
    <nct_id>NCT04499612</nct_id>
  </id_info>
  <brief_title>Influence of Cardiac Implantable Electronic Devices on the Hemostatic System</brief_title>
  <official_title>Assessment of the Hemostatic System, Thromboembolic Complications and Cardiovascular Events in Patients With Cardiovascular Implantable Electronic Devices</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ryazan State Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ryazan State Medical University</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>
      The hemostasis system is one of the many biological systems of the human body, designed to&#xD;
      preserve the liquid state of blood and prevent its loss during vascular injuries. The ideal&#xD;
      balance between its coagulant and anticoagulant components never occurs. In various diseases&#xD;
      and pathological conditions, the balance of the hemostasis system may be disturbed. Shifts&#xD;
      towards hypercoagulability lead to the development of hemorrhagic complications, opposite&#xD;
      shifts lead to the development of thrombotic complications.&#xD;
&#xD;
      Patients with cardiac implantable electronic devices (CIED) are not rare and unique, today&#xD;
      doctors meet with them every day. Its more than 1.5 million CIED's implanted every year.&#xD;
&#xD;
      Before surgery these patients are standard cardiology department patients with chronic heart&#xD;
      failure (CHF), which develops due to the presence of arrhythmias, coronary heart disease,&#xD;
      hypertension, congenital heart disease, myocardial infarction, myocarditis or other diseases&#xD;
      and conditions. CHF is the most common, severe and unfavorable prognostic complication of&#xD;
      these diseases. With CHF, the balance of the hemostasis system shifts towards&#xD;
      hypercoagulation. Patients with CHF have an increased risk of arterial and venous thrombosis,&#xD;
      pulmonary embolism, myocardial infarction, stroke, numerous brady- and tachyarrhythmias and&#xD;
      other complications.&#xD;
&#xD;
      After CIED implantation, bradyarrhythmia is eliminated, as one of the parts in the&#xD;
      pathogenesis of CHF. Patients, especially those with severe symptoms, improve their condition&#xD;
      in the early postoperative period. In the long-term period, pacing, on the contrary, may&#xD;
      contribute to the progression of CHF. The wrong choice of pacing mode or the place of&#xD;
      electrode implantation can lead to desynchronization of the heart chambers, myocardial&#xD;
      remodeling and left ventricular dysfunction.&#xD;
&#xD;
      Uncertainty is also observed in relation to the hemostasis system after CIED implantation. On&#xD;
      the one hand, correction of bradyarrhythmia and CHF should provide patients with a shift&#xD;
      towards hypocoagulability by normalizing the heart rate. On the other hand, trauma to the&#xD;
      vessel wall during surgery, further placement of the CIED leads in the vessels, and&#xD;
      perioperative stress can lead to even greater shifts towards hypercoagulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      250 patients of similar age, gender, and ethnicity will be divided into five groups: Group&#xD;
      A1-3: 150 patients with indications for cardiac implantable electronic device (CIED)&#xD;
      implantation; Group B: 50 patients with an CIED implanted 8-10 years ago; Group C: 50&#xD;
      patients with diseases similar to group A, but without indications for CIED implantation;&#xD;
      Patients will be followed up for 2 years. Patients of group A1-3 will be taken peripheral&#xD;
      venous blood to assess the studied parameters of hemostasis (platelet count, plateletcrit,&#xD;
      mean platelet volume, platelet distribution width, von Willebrand factor, P-selectin,&#xD;
      coagulation factor I (FI), coagulation factor II (FII), coagulation factor V (FV),&#xD;
      coagulation factor VII (FVII), coagulation factor X (FX), coagulation factor VIII (FVIII),&#xD;
      coagulation factor IX (FIX), coagulation factor XI (FXI), coagulation factor XII (FXII),&#xD;
      plasminogen, soluble fibrin, plasminogen activator inhibitor-1 (PAI-1), D-dimer, antithrombin&#xD;
      III, protein C) and duplex ultrasound of the vessels of the upper and lower extremities&#xD;
      before the operation, after 7 days, 1 and 12 months after the operation. Similar procedures&#xD;
      will be performed for patients of groups B and C only when included in the study.&#xD;
      Echocardiography will be performed on all patients at enrollment, after 12 and 24 months of&#xD;
      follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2020</start_date>
  <completion_date type="Anticipated">March 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2024</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>Development of thromboembolism: venous thrombosis, pulmonary embolism, arterial thrombosis, arterial thromboembolism, transient ischemic attack, stroke.</measure>
    <time_frame>Up to 2 years after enrollment (according to the study design).</time_frame>
    <description>Development of thromboembolic complications after the cardiac implantable electronic device implantation/replace or thromboembolism in conservative group patients during observation period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Development of cardiovascular event: myocardial infarction, acute coronary syndrome, atrial fibrillation, decompensation of chronic heart failure.</measure>
    <time_frame>Up to 2 years after enrollment (according to the study design).</time_frame>
    <description>Development of cardiovascular events after the cardiac implantable electronic device implantation/replace or in conservative group patients during observation period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemostasis system markers deviations.</measure>
    <time_frame>Up to 2 years after enrollment (according to the study design).</time_frame>
    <description>Deviation of investigated markers of the hemostasis system from normal values.</description>
  </secondary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Thromboembolism</condition>
  <condition>Cardiac Event</condition>
  <condition>Hemostatic Disorder</condition>
  <arm_group>
    <arm_group_label>Group &quot;Single-chamber CIED&quot; (A1)</arm_group_label>
    <description>50 patients with permanent atrial fibrillation and indications for cardiac implantable electronic device implantation (single-chamber system).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group &quot;Dual-chamber CIED&quot; (A2)</arm_group_label>
    <description>50 patients with atrioventricular block/sick sinus syndrome and indications for cardiac implantable electronic device implantation (dual-chamber system).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group &quot;Dual-chamber CIED + Atrial fibrillation&quot; (A3)</arm_group_label>
    <description>50 patients with atrioventricular block/sick sinus syndrome, paroxysmal or persistent atrial fibrillation and indications for cardiac implantable electronic device implantation (dual-chamber system).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group &quot;CIED Replace&quot; (B)</arm_group_label>
    <description>50 patients with cardiac implantable electronic device implantation 6-12 years ago (single- or dual-chamber system).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group &quot;Conservative&quot; (C)</arm_group_label>
    <description>50 patients with atrioventricular block/sick sinus syndrome/atrial fibrillation and without indications for cardiac implantable electronic device implantation (conservative group).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cardiac implantable electronic device implantation.</intervention_name>
    <description>Patients who have indications will receive cardiac implantable electronic device implantation.</description>
    <arm_group_label>Group &quot;Dual-chamber CIED + Atrial fibrillation&quot; (A3)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED&quot; (A2)</arm_group_label>
    <arm_group_label>Group &quot;Single-chamber CIED&quot; (A1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cardiac implantable electronic device replace.</intervention_name>
    <description>Patients who have indications will receive cardiac implantable electronic device replace.</description>
    <arm_group_label>Group &quot;CIED Replace&quot; (B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Duplex ultrasound.</intervention_name>
    <description>Patients will undergo ultrasound examination of the vessels of the upper and lower extremities.</description>
    <arm_group_label>Group &quot;CIED Replace&quot; (B)</arm_group_label>
    <arm_group_label>Group &quot;Conservative&quot; (C)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED + Atrial fibrillation&quot; (A3)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED&quot; (A2)</arm_group_label>
    <arm_group_label>Group &quot;Single-chamber CIED&quot; (A1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Echocardiography.</intervention_name>
    <description>Patients will undergo an ultrasound examination of the heart.</description>
    <arm_group_label>Group &quot;CIED Replace&quot; (B)</arm_group_label>
    <arm_group_label>Group &quot;Conservative&quot; (C)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED + Atrial fibrillation&quot; (A3)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED&quot; (A2)</arm_group_label>
    <arm_group_label>Group &quot;Single-chamber CIED&quot; (A1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood sampling.</intervention_name>
    <description>Patients will be taken venous blood to determine the studied markers of hemostasis system.</description>
    <arm_group_label>Group &quot;CIED Replace&quot; (B)</arm_group_label>
    <arm_group_label>Group &quot;Conservative&quot; (C)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED + Atrial fibrillation&quot; (A3)</arm_group_label>
    <arm_group_label>Group &quot;Dual-chamber CIED&quot; (A2)</arm_group_label>
    <arm_group_label>Group &quot;Single-chamber CIED&quot; (A1)</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing treatment in cardiology and cardiac surgery departments who have an&#xD;
        implanted cardiac implantable electronic device or have indication/no indication for&#xD;
        cardiac implantable electronic device implantation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  for group A1-3: atrioventricular block/sick sinus syndrome/atrial fibrillation with&#xD;
             impaired conduction as indications for cardiac implantable electronic device&#xD;
             implantation;&#xD;
&#xD;
          -  for group B: atrioventricular block/sick sinus syndrome/atrial fibrillation with&#xD;
             impaired conduction and cardiac implantable electronic device implanted 6-12 years&#xD;
             ago;&#xD;
&#xD;
          -  for group C: atrioventricular block/sick sinus syndrome/atrial fibrillation with&#xD;
             impaired conduction without indications for cardiac implantable electronic device&#xD;
             implantation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  active cancer or a remission period of less than 5 years;&#xD;
&#xD;
          -  decompensated somatic pathology;&#xD;
&#xD;
          -  pregnancy or breastfeeding in women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Igor A. Suchkov, MD, DSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ryazan State Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vladislav O. Povarov, MD, PhD</last_name>
    <phone>+7-915-602-7478</phone>
    <email>povarov.vladislav@mail.ru</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Igor A. Suchkov, MD, DSc</last_name>
    <phone>+7-903-836-2417</phone>
    <email>suchkov_med@mail.ru</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ryazan State Medical University</name>
      <address>
        <city>Ryazan'</city>
        <state>Ryazan</state>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Igor A. Suchkov, MD, DSc</last_name>
      <phone>+7-903-836-2417</phone>
      <email>suchkov_med@mail.ru</email>
    </contact>
    <investigator>
      <last_name>Vladislav O. Povarov, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <reference>
    <citation>Kalinin RE, Suchkov IA, Shitov II, Mzhavanadze ND, Povarov VO. [Venous thromboembolic complications in patients with cardiovascular implantable electronic devices]. Angiol Sosud Khir. 2017;23(4):69-74. Russian.</citation>
    <PMID>29240058</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>July 20, 2023</last_update_submitted>
  <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiac implantable electronic devices</keyword>
  <keyword>Pacing</keyword>
  <keyword>Hemostasis</keyword>
  <keyword>Thromboembolism</keyword>
  <keyword>Cardiovascular events</keyword>
  <keyword>Arrhythmias</keyword>
  <keyword>Atrial fibrillation</keyword>
  <keyword>Chronic heart failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Hemostatic Disorders</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Basic demographic data, including sex, age, and ethnicity are to be shared if allowed by the privacy policy.</ipd_description>
  </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/NCT04499612
org study id: 05/290120
nct id: NCT04499612
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The hemostasis system is one of the many biological systems of the human body, designed to
      preserve the liquid state of blood and prevent its loss during vascular injuries. The ideal
      balance between its coagulant and anticoagulant components never occurs. In various diseases
      and pathological conditions, the balance of the hemostasis system may be disturbed. Shifts
      towards hypercoagulability lead to the development of hemorrhagic complications, opposite
      shifts lead to the development of thrombotic complications.

      Patients with cardiac implantable electronic devices (CIED) are not rare and unique, today
      doctors meet with them every day. Its more than 1.5 million CIED's implanted every year.

      Before surgery these patients are standard cardiology department patients with chronic heart
      failure (CHF), which develops due to the presence of arrhythmias, coronary heart disease,
      hypertension, congenital heart disease, myocardial infarction, myocarditis or other diseases
      and conditions. CHF is the most common, severe and unfavorable prognostic complication of
      these diseases. With CHF, the balance of the hemostasis system shifts towards
      hypercoagulation. Patients with CHF have an increased risk of arterial and venous thrombosis,
      pulmonary embolism, myocardial infarction, stroke, numerous brady- and tachyarrhythmias and
      other complications.

      After CIED implantation, bradyarrhythmia is eliminated, as one of the parts in the
      pathogenesis of CHF. Patients, especially those with severe symptoms, improve their condition
      in the early postoperative period. In the long-term period, pacing, on the contrary, may
      contribute to the progression of CHF. The wrong choice of pacing mode or the place of
      electrode implantation can lead to desynchronization of the heart chambers, myocardial
      remodeling and left ventricular dysfunction.

      Uncertainty is also observed in relation to the hemostasis system after CIED implantation. On
      the one hand, correction of bradyarrhythmia and CHF should provide patients with a shift
      towards hypocoagulability by normalizing the heart rate. On the other hand, trauma to the
      vessel wall during surgery, further placement of the CIED leads in the vessels, and
      perioperative stress can lead to even greater shifts towards hypercoagulation.
250 patients of similar age, gender, and ethnicity will be divided into five groups: Group
      A1-3: 150 patients with indications for cardiac implantable electronic device (CIED)
      implantation; Group B: 50 patients with an CIED implanted 8-10 years ago; Group C: 50
      patients with diseases similar to group A, but without indications for CIED implantation;
      Patients will be followed up for 2 years. Patients of group A1-3 will be taken peripheral
      venous blood to assess the studied parameters of hemostasis (platelet count, plateletcrit,
      mean platelet volume, platelet distribution width, von Willebrand factor, P-selectin,
      coagulation factor I (FI), coagulation factor II (FII), coagulation factor V (FV),
      coagulation factor VII (FVII), coagulation factor X (FX), coagulation factor VIII (FVIII),
      coagulation factor IX (FIX), coagulation factor XI (FXI), coagulation factor XII (FXII),
      plasminogen, soluble fibrin, plasminogen activator inhibitor-1 (PAI-1), D-dimer, antithrombin
      III, protein C) and duplex ultrasound of the vessels of the upper and lower extremities
      before the operation, after 7 days, 1 and 12 months after the operation. Similar procedures
      will be performed for patients of groups B and C only when included in the study.
      Echocardiography will be performed on all patients at enrollment, after 12 and 24 months of
      follow-up.
observational model: Cohort
time perspective: Prospective
measure: Development of thromboembolism: venous thrombosis, pulmonary embolism, arterial thrombosis, arterial thromboembolism, transient ischemic attack, stroke.
time frame: Up to 2 years after enrollment (according to the study design).
description: Development of thromboembolic complications after the cardiac implantable electronic device implantation/replace or thromboembolism in conservative group patients during observation period.
measure: Development of cardiovascular event: myocardial infarction, acute coronary syndrome, atrial fibrillation, decompensation of chronic heart failure.
time frame: Up to 2 years after enrollment (according to the study design).
description: Development of cardiovascular events after the cardiac implantable electronic device implantation/replace or in conservative group patients during observation period.
measure: Hemostasis system markers deviations.
time frame: Up to 2 years after enrollment (according to the study design).
description: Deviation of investigated markers of the hemostasis system from normal values.
arm group label: Group "Single-chamber CIED" (A1)
description: 50 patients with permanent atrial fibrillation and indications for cardiac implantable electronic device implantation (single-chamber system).
arm group label: Group "Dual-chamber CIED" (A2)
description: 50 patients with atrioventricular block/sick sinus syndrome and indications for cardiac implantable electronic device implantation (dual-chamber system).
arm group label: Group "Dual-chamber CIED + Atrial fibrillation" (A3)
description: 50 patients with atrioventricular block/sick sinus syndrome, paroxysmal or persistent atrial fibrillation and indications for cardiac implantable electronic device implantation (dual-chamber system).
arm group label: Group "CIED Replace" (B)
description: 50 patients with cardiac implantable electronic device implantation 6-12 years ago (single- or dual-chamber system).
arm group label: Group "Conservative" (C)
description: 50 patients with atrioventricular block/sick sinus syndrome/atrial fibrillation and without indications for cardiac implantable electronic device implantation (conservative group).
intervention type: Procedure
intervention name: Cardiac implantable electronic device implantation.
description: Patients who have indications will receive cardiac implantable electronic device implantation.
arm group label: Group "Dual-chamber CIED + Atrial fibrillation" (A3)
arm group label: Group "Dual-chamber CIED" (A2)
arm group label: Group "Single-chamber CIED" (A1)
intervention type: Procedure
intervention name: Cardiac implantable electronic device replace.
description: Patients who have indications will receive cardiac implantable electronic device replace.
arm group label: Group "CIED Replace" (B)
intervention type: Diagnostic Test
intervention name: Duplex ultrasound.
description: Patients will undergo ultrasound examination of the vessels of the upper and lower extremities.
arm group label: Group "CIED Replace" (B)
arm group label: Group "Conservative" (C)
arm group label: Group "Dual-chamber CIED + Atrial fibrillation" (A3)
arm group label: Group "Dual-chamber CIED" (A2)
arm group label: Group "Single-chamber CIED" (A1)
intervention type: Diagnostic Test
intervention name: Echocardiography.
description: Patients will undergo an ultrasound examination of the heart.
arm group label: Group "CIED Replace" (B)
arm group label: Group "Conservative" (C)
arm group label: Group "Dual-chamber CIED + Atrial fibrillation" (A3)
arm group label: Group "Dual-chamber CIED" (A2)
arm group label: Group "Single-chamber CIED" (A1)
intervention type: Diagnostic Test
intervention name: Blood sampling.
description: Patients will be taken venous blood to determine the studied markers of hemostasis system.
arm group label: Group "CIED Replace" (B)
arm group label: Group "Conservative" (C)
arm group label: Group "Dual-chamber CIED + Atrial fibrillation" (A3)
arm group label: Group "Dual-chamber CIED" (A2)
arm group label: Group "Single-chamber CIED" (A1)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Igor A. Suchkov, MD, DSc
role: Principal Investigator
affiliation: Ryazan State Medical University
last name: Vladislav O. Povarov, MD, PhD
phone: +7-915-602-7478
email: povarov.vladislav@mail.ru
last name: Igor A. Suchkov, MD, DSc
phone: +7-903-836-2417
email: suchkov_med@mail.ru
facility: 
status: Recruiting
contact: 
investigator: 
country: Russian Federation
citation: Kalinin RE, Suchkov IA, Shitov II, Mzhavanadze ND, Povarov VO. [Venous thromboembolic complications in patients with cardiovascular implantable electronic devices]. Angiol Sosud Khir. 2017;23(4):69-74. Russian.
PMID: 29240058
responsible party type: Sponsor
mesh term: Thromboembolism
mesh term: Cardiovascular Diseases
mesh term: Hemostatic Disorders
mesh term: Blood Coagulation Disorders
sharing ipd: Undecided
ipd description: Basic demographic data, including sex, age, and ethnicity are to be shared if allowed by the privacy policy.