xml: <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/NCT05992259</url>
    </required_header>
    <id_info>
      <org_study_id>#12</org_study_id>
      <nct_id>NCT05992259</nct_id>
    </id_info>
    <brief_title>Auricular Vagus Stimulation and STEMI</brief_title>
    <official_title>Auricular Vagus Stimulation and ST-Segment Elevation Myocardial Infarction</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Bakulev Scientific Center of Cardiovascular Surgery</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Bakulev Scientific Center of Cardiovascular Surgery</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        At the moment, the invasive strategy for the infarct-associated coronary artery in patients&#xD;
        with ST-segment elevation myocardial infarction (STEMI) necessary to save the myocardium and&#xD;
        reduce the size of the necrosis zone remains the leading one. However, despite the high&#xD;
        efficiency of providing medical care to patients with acute coronary syndrome (ACS), there&#xD;
        remains a high mortality and disability of this group of patients. In this regard, the search&#xD;
        for new drug and non-drug strategies for the treatment of patients with ACS is actively&#xD;
        continuing. Over the past decade, it has been shown that transcutaneous vagus nerve&#xD;
        stimulation (TENS) has a cardioprotective effect both in chronic heart failure and in&#xD;
        coronary heart disease, improves cardiac function, prevents reperfusion injury, weakens&#xD;
        myocardial remodeling, increases the effectiveness of defibrillation and reduces the size of&#xD;
        a heart attack. One of the methods of noninvasive stimulation of the afferent fibers of the&#xD;
        vagus nerve is percutaneous electrical stimulation of the auricular branch of the vagus&#xD;
        nerve. However, further studies are needed to determine whether stimulation of the tragus can&#xD;
        improve the long-term clinical outcome in this cohort of patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        ACS is a combined concept for such life-threatening conditions as acute myocardial infarction&#xD;
        (AMI) and unstable angina, which are exacerbations of coronary heart disease. However,&#xD;
        despite the high effectiveness of the invasive treatment strategy, there remains a high&#xD;
        mortality and disability of this group of patients. One of the reasons for this problem is&#xD;
        reperfusion injury of the myocardium during revascularization, since reperfusion itself&#xD;
        causes myocardial damage, known as Myocardial Ischemia Reperfusion Injury (MIRI). Every year,&#xD;
        new data from experimental studies and small clinical trials appear, confirming the concept&#xD;
        that MIRI makes a big contribution to the final size of a heart attack and cardiac myocardial&#xD;
        function. Currently, there is no specific treatment aimed at MIRI in patients with STEMI.&#xD;
        Thus, new treatment methods are needed that can reduce MIRI in revascularized patients. In&#xD;
        the course of small clinical studies, it was shown that against the background of vagus nerve&#xD;
        stimulation, a significant decrease in heart rate occurs, inflammatory processes and cellular&#xD;
        apoptosis are suppressed, left ventricular remodeling decreases and myocardial contractile&#xD;
        function improves. Also, a significant decrease in MIRI is demonstrated with percutaneous&#xD;
        stimulation of the vagus nerve in the acute period of myocardial infarction. The data of the&#xD;
        first clinical trial with VNS in patients with STEMI were published in 2017&#xD;
        (doi:10.1016/j.jcin.2017.04.036). This experimental study increases the likelihood that this&#xD;
        noninvasive therapy can be used to treat patients with STEMI who are undergoing primary&#xD;
        percutaneous coronary intervention (PCI). New studies are needed to prove the safety and&#xD;
        effectiveness of vagus nerve stimulation in patients with STEMI.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 1, 2022</start_date>
    <completion_date type="Anticipated">December 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>1:1 randomization of active stimulation vs. sham stimulation</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Hospital mortality</measure>
      <time_frame>From date of randomization until the date of death from any cause, assessed up to 14 days.</time_frame>
      <description>The number of patients who died in the hospital.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>30-day mortality</measure>
      <time_frame>From date of randomization until the date of death from any cause, assessed up to 30 days.</time_frame>
      <description>The number of patients who died within 30 days from the development of myocardial infarction.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of participants with non-lethal events.</measure>
      <time_frame>From the date of randomization to the date of any of the listed events, assessed up to 14 days.</time_frame>
      <description>The main hospital non-lethal events (Pulmonary edema, Cardiogenic shock, Cardiac arrhythmias: Atrial fibrillation, Ventricular tachycardia/fibrillation, Accelerated idioventricular rhythm/Atrioventricular block II, III).</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Assessment of the level of myocardial damage.</measure>
      <time_frame>Diagnosis will be carried out during hospitalization, after 6 hours and on the 4th day of hospitalization.</time_frame>
      <description>Dynamics of Troponin I (hs-cTnI) in blood plasma.</description>
    </other_outcome>
    <other_outcome>
      <measure>Assessment of the level of inflammation.</measure>
      <time_frame>Diagnosis will be carried out during hospitalization and after 24 hours.</time_frame>
      <description>Dynamics of high-sensitivity C-reactive protein (hs-CRP) in blood plasma. Dynamics of copeptin (CPP) in blood plasma.</description>
    </other_outcome>
    <other_outcome>
      <measure>Assessment of the level of heart failure</measure>
      <time_frame>Diagnosis will be carried out during hospitalization and on the 4th day of hospitalization.</time_frame>
      <description>Dynamics of NT-proBNP in blood plasma.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Vagus Nerve Stimulation</condition>
    <condition>Acute Coronary Syndrome</condition>
    <condition>Ischemia Reperfusion Injury</condition>
    <arm_group>
      <arm_group_label>Active TENS</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>It will be performed attached to the tragus of the left ear.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham TENS</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>It will be performed attached to the earlobe of the left ear.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>TENS</intervention_name>
      <description>TENS will be performed from the moment of admission to the PCI, during the PCI and for the next 30 minutes after it.</description>
      <arm_group_label>Active TENS</arm_group_label>
      <arm_group_label>Sham TENS</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  patients with STEMI who have signed an informed voluntary consent to participate in&#xD;
               the study;&#xD;
  &#xD;
            -  primary myocardial infarction;&#xD;
  &#xD;
            -  treatment in the first 12 hours from the onset of pain syndrome;&#xD;
  &#xD;
            -  primary PCI.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  acute heart failure III-IV;&#xD;
  &#xD;
            -  bradyarrhythmias;&#xD;
  &#xD;
            -  atrial fibrillation/flutter at the time of switching on;&#xD;
  &#xD;
            -  Thrombolytic therapy at the prehospital stage;&#xD;
  &#xD;
            -  a history of myocardial infarction;&#xD;
  &#xD;
            -  PCI/coronary artery bypass grafting (CABG) in the anamnesis.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Vladimir Shvartz, MD, DM</last_name>
      <role>Principal Investigator</role>
      <affiliation>Bakoulev Scientific Center for Cardiovascular Surgery</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Vladimir Shvartz, MD, DM</last_name>
      <phone>+79032619292</phone>
      <email>vashvarts@bakulev.ru</email>
    </overall_contact>
    <location>
      <facility>
        <name>Scientific Research Institute Ochapovsky Regional Clinical Hospital</name>
        <address>
          <city>Krasnodar</city>
          <country>Russian Federation</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Sofia Kruchinova, MD, PhD</last_name>
        <phone>+79189504597</phone>
        <email>skruchinova@mail.ru</email>
      </contact>
    </location>
    <location_countries>
      <country>Russian Federation</country>
    </location_countries>
    <link>
      <url>https://doi.org/10.1016/j.jcin.2017.04.036</url>
      <description>Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study</description>
    </link>
    <link>
      <url>https://doi.org/10.1016/j.jcin.2017.05.063</url>
      <description>Vagal Cardioprotection in Reperfused Acute Myocardial Infarction</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Bakulev Scientific Center of Cardiovascular Surgery</investigator_affiliation>
      <investigator_full_name>Vladimir A Shvartz, MD</investigator_full_name>
      <investigator_title>MD, DM, Professor</investigator_title>
    </responsible_party>
    <keyword>auricular stimulation</keyword>
    <keyword>auricular vagus nerve stimulation</keyword>
    <keyword>transcutaneous vagus nerve stimulation (TENS)</keyword>
    <keyword>vagus nerve stimulation (VNS)</keyword>
    <keyword>acute coronary syndrome</keyword>
    <keyword>myocardial ischemia reperfusion injury</keyword>
    <keyword>ST-segment elevation myocardial infarction</keyword>
    <keyword>coronary heart disease</keyword>
    <keyword>acute myocardial infarction</keyword>
    <keyword>mortality</keyword>
    <keyword>atrial fibrillation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Myocardial Infarction</mesh_term>
      <mesh_term>Acute Coronary Syndrome</mesh_term>
      <mesh_term>Reperfusion Injury</mesh_term>
      <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
      <mesh_term>Ischemia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05992259
  org study id: #12
  nct id: NCT05992259
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  At the moment, the invasive strategy for the infarct-associated coronary artery in patients
        with ST-segment elevation myocardial infarction (STEMI) necessary to save the myocardium and
        reduce the size of the necrosis zone remains the leading one. However, despite the high
        efficiency of providing medical care to patients with acute coronary syndrome (ACS), there
        remains a high mortality and disability of this group of patients. In this regard, the search
        for new drug and non-drug strategies for the treatment of patients with ACS is actively
        continuing. Over the past decade, it has been shown that transcutaneous vagus nerve
        stimulation (TENS) has a cardioprotective effect both in chronic heart failure and in
        coronary heart disease, improves cardiac function, prevents reperfusion injury, weakens
        myocardial remodeling, increases the effectiveness of defibrillation and reduces the size of
        a heart attack. One of the methods of noninvasive stimulation of the afferent fibers of the
        vagus nerve is percutaneous electrical stimulation of the auricular branch of the vagus
        nerve. However, further studies are needed to determine whether stimulation of the tragus can
        improve the long-term clinical outcome in this cohort of patients.
  ACS is a combined concept for such life-threatening conditions as acute myocardial infarction
        (AMI) and unstable angina, which are exacerbations of coronary heart disease. However,
        despite the high effectiveness of the invasive treatment strategy, there remains a high
        mortality and disability of this group of patients. One of the reasons for this problem is
        reperfusion injury of the myocardium during revascularization, since reperfusion itself
        causes myocardial damage, known as Myocardial Ischemia Reperfusion Injury (MIRI). Every year,
        new data from experimental studies and small clinical trials appear, confirming the concept
        that MIRI makes a big contribution to the final size of a heart attack and cardiac myocardial
        function. Currently, there is no specific treatment aimed at MIRI in patients with STEMI.
        Thus, new treatment methods are needed that can reduce MIRI in revascularized patients. In
        the course of small clinical studies, it was shown that against the background of vagus nerve
        stimulation, a significant decrease in heart rate occurs, inflammatory processes and cellular
        apoptosis are suppressed, left ventricular remodeling decreases and myocardial contractile
        function improves. Also, a significant decrease in MIRI is demonstrated with percutaneous
        stimulation of the vagus nerve in the acute period of myocardial infarction. The data of the
        first clinical trial with VNS in patients with STEMI were published in 2017
        (doi:10.1016/j.jcin.2017.04.036). This experimental study increases the likelihood that this
        noninvasive therapy can be used to treat patients with STEMI who are undergoing primary
        percutaneous coronary intervention (PCI). New studies are needed to prove the safety and
        effectiveness of vagus nerve stimulation in patients with STEMI.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: 1:1 randomization of active stimulation vs. sham stimulation
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Hospital mortality
  time frame: From date of randomization until the date of death from any cause, assessed up to 14 days.
  description: The number of patients who died in the hospital.
  measure: 30-day mortality
  time frame: From date of randomization until the date of death from any cause, assessed up to 30 days.
  description: The number of patients who died within 30 days from the development of myocardial infarction.
  measure: Number of participants with non-lethal events.
  time frame: From the date of randomization to the date of any of the listed events, assessed up to 14 days.
  description: The main hospital non-lethal events (Pulmonary edema, Cardiogenic shock, Cardiac arrhythmias: Atrial fibrillation, Ventricular tachycardia/fibrillation, Accelerated idioventricular rhythm/Atrioventricular block II, III).
  measure: Assessment of the level of myocardial damage.
  time frame: Diagnosis will be carried out during hospitalization, after 6 hours and on the 4th day of hospitalization.
  description: Dynamics of Troponin I (hs-cTnI) in blood plasma.
  measure: Assessment of the level of inflammation.
  time frame: Diagnosis will be carried out during hospitalization and after 24 hours.
  description: Dynamics of high-sensitivity C-reactive protein (hs-CRP) in blood plasma. Dynamics of copeptin (CPP) in blood plasma.
  measure: Assessment of the level of heart failure
  time frame: Diagnosis will be carried out during hospitalization and on the 4th day of hospitalization.
  description: Dynamics of NT-proBNP in blood plasma.
  arm group label: Active TENS
  arm group type: Active Comparator
  description: It will be performed attached to the tragus of the left ear.
  arm group label: Sham TENS
  arm group type: Sham Comparator
  description: It will be performed attached to the earlobe of the left ear.
  intervention type: Device
  intervention name: TENS
  description: TENS will be performed from the moment of admission to the PCI, during the PCI and for the next 30 minutes after it.
  arm group label: Active TENS
  arm group label: Sham TENS
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Vladimir Shvartz, MD, DM
  role: Principal Investigator
  affiliation: Bakoulev Scientific Center for Cardiovascular Surgery
  last name: Vladimir Shvartz, MD, DM
  phone: +79032619292
  email: vashvarts@bakulev.ru
  facility: 
  status: Recruiting
  contact: 
  country: Russian Federation
  url: https://doi.org/10.1016/j.jcin.2017.04.036
  description: Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study
  url: https://doi.org/10.1016/j.jcin.2017.05.063
  description: Vagal Cardioprotection in Reperfused Acute Myocardial Infarction
  responsible party type: Principal Investigator
  investigator affiliation: Bakulev Scientific Center of Cardiovascular Surgery
  investigator full name: Vladimir A Shvartz, MD
  investigator title: MD, DM, Professor
  mesh term: Myocardial Infarction
  mesh term: Acute Coronary Syndrome
  mesh term: Reperfusion Injury
  mesh term: ST Elevation Myocardial Infarction
  mesh term: Ischemia
  sharing ipd: No