<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/NCT04448639</url>
  </required_header>
  <id_info>
    <org_study_id>Dnr 2019-04092</org_study_id>
    <nct_id>NCT04448639</nct_id>
  </id_info>
  <brief_title>Stunning in Takotsubo Versus Acute Myocardial Infarction</brief_title>
  <acronym>STAMI</acronym>
  <official_title>STAMI- Stunning in Takotsubo Versus Acute Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vastra Gotaland Region</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vastra Gotaland Region</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 Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) Study&#xD;
&#xD;
      Background: Acute myocardial stunning, herein defined as the reversible loss of myocardial&#xD;
      function, occurs in both takotsubo syndrome (TS) and ST-elevation myocardial infarction&#xD;
      (STEMI), and can be life-threatening in both conditions. However, despite typically having&#xD;
      considerably more pronounced myocardial stunning, TS patients have better prognosis than&#xD;
      patients with STEMI. Despite the different relationship between extent of myocardial stunning&#xD;
      and prognosis in TS vs STEMI, no 'head-to-head' comparison of the myocardial stunning&#xD;
      phenotypes in TS vs STEMI has been done.&#xD;
&#xD;
      Methods: The Stunning In Takotsubo and Acute Myocardial Infarction (STAMI) study is a&#xD;
      single-center, prospective clinical study that will enroll 100 patients with STEMI and 25&#xD;
      patients with TS. Echocardiography, laboratory testing (including troponin and NTpro-BNP),&#xD;
      and ECG will be done immediately after angiography and at days 1, 2, 3, 7, 14 and 30. The&#xD;
      primary endpoint is the proportion of myocardial stunning that has resolved after 72 hours,&#xD;
      as determined by echocardiography. Total myocardial stunning is defined as the extent of&#xD;
      akinesia observed at day 0 that resolves by day 30.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective assessment of the temporal electrocardiographic-, vectorcardiographic- and&#xD;
      echocardiographic changes in STelevation myocardial infarction versus the takotsubo syndrome.&#xD;
&#xD;
      AIM To compare the temporal pattern of myocardial funtional recovery after ST-elevation&#xD;
      myocardial infarction (STEMI) versus the takotsubo syndrome (TS).&#xD;
&#xD;
      BACKGROUND Modern therapies have reduced the incidence of acute ischemic heart failure (AIHF)&#xD;
      -But AIHF is still common and once it develops prognosis remains dismal.Despite considerable&#xD;
      therapeutic advancements over the last decades, acute myocardialinfarction (AMI) remains one&#xD;
      of the most common causes of death . Among patients who are admitted with AMI, the 10% that&#xD;
      develop AIHF account for approximately 50% of Deaths within 30 days . The prognosis for&#xD;
      patients with AIHF has not improved over the last decade . AIHF occurs due to acute loss of&#xD;
      cardiac function, some of which occurs in myocardium that is not irreparably damaged - so&#xD;
      called stunned myocardium.&#xD;
&#xD;
      Myocardial stunning in AIHF - Temporary mechanical dysfunction without irreparable injury.&#xD;
      Myocardial stunning was originally described in the setting of ischemia and was defined as&#xD;
      temporary mechanical dysfunction that persists after resolution of ischemia, with the absence&#xD;
      of irreversible histological damage . For the purpose of this application it is more broadly&#xD;
      defined as temporary mechanical dysfunction, with the absence of irreversible histological&#xD;
      damage - irrespective of the underlying cause. Myocardial stunning is believed to be a&#xD;
      harmful phenomenon caused by cellular injury .&#xD;
&#xD;
      Study hypothesis: Myocardial stunning is a protective mechanism by which the cardiomyocytes&#xD;
      preserve energy for vital processes in states of severe cellular stress - but that can&#xD;
      &quot;overshoot&quot; and lead to potentially lethal cardiac decompensation. In the normal heart, the&#xD;
      contractile apparatus consumes the majority of myocardial energy and oxygen . Non-contractile&#xD;
      myocardial functions, including cellular and electrical homeostasis, require less than 20% as&#xD;
      much oxygen. When oxygen supply to the heart is interrupted myocardial stunning ensues within&#xD;
      seconds, whereas it takes at least 10 minutes for the cardiomyocyte's energy metabolites to&#xD;
      decrease to 50% of their initial level .Hence, by shutting down the contractile apparatus&#xD;
      before it consumes the cells' energy stores myocardial stunning effectively preserves energy&#xD;
      for processes that are necessary for cell survival . Irrespective of its beneficial effects&#xD;
      on cardiomyocyte metabolism, myocardial stunning may lead to sufficiently pronounced cardiac&#xD;
      dysfunction to cause life-threatening AIHF.&#xD;
&#xD;
      Study purpose:&#xD;
&#xD;
      To better understand the difference between myocardial stunning in STEMI and the more benign&#xD;
      form of stunning in TS. The sudden occurrence of temporary myocardial mechanical dysfunction&#xD;
      with the absence of irreversible myocardial damage is not limited to AMI. It can occur&#xD;
      postoperatively after cardiac arrest; in the settings of acute myocarditis and&#xD;
      tachycardia-induced cardiomyopathy; and as a consequence of severe emotional or somatic&#xD;
      stress in the takotsubo syndrome .Intriguingly, takotsubo is characterized by a compensated&#xD;
      hemodynamic profile despite extensive myocardial dysfunction, effective recovery of&#xD;
      myocardial function within days orweeks, and a relatively good prognosis .Takotsubo therefore&#xD;
      appears to be a more efficient form of stunning than AIHF. Better understanding of the&#xD;
      mechanisms behind the stunning phenomenon could allow for manipulation of the stunning&#xD;
      phenotype in AIHF, or for pharmacological reversal of myocardial stunning once coronary&#xD;
      reperfusion and adequate myocardial energy delivery has been ensured.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 12, 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of stunning that has resolved at 3 days versus 14 days</measure>
    <time_frame>30 days</time_frame>
    <description>StunningResolution at 3 days is defined as StunningRes3D = (%Akinesia Baseline - %Akinesia 3day) / (%Akinesia Baseline -&#xD;
%Akinesia 30days); where %Akinesia is calculated as the endocardial length of the akinetic left ventricular myocardium divided by the total endocardial length of the left ventricular myoocardium - as assessed in the apical 2-chamber and 4-chamber views at end-diastole.&#xD;
The recovery of stunning at 3 days is compared to the recovery of stunning at 30 days. Thus a 14 day timeframe is required.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative increase in global longitudinal strain at 3 days vs index</measure>
    <time_frame>3 days</time_frame>
    <description>Global longitudinal strain as measured by speckle tracking echocardiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global longitudinal strain at 0, 1, 2, 3, 7, 14 and 30 days</measure>
    <time_frame>Days 0, 1, 2, 3, 7, 14, 30 days</time_frame>
    <description>Global longitudinal strain as measured by speckle tracking echocardiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional radial strain in the unaffected contralateral myocardial wall at days 0, 1, 2, 3, 7, 14 and 30</measure>
    <time_frame>Days 0, 1, 2, 3, 7, 14 and 30</time_frame>
    <description>Radial longitudinal strain as measured by speckle tracking echocardiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major adverse cardiac events at 30 days and 1 year</measure>
    <time_frame>Days 30 and 365</time_frame>
    <description>Major adverse cardiac event is defined as all-cause death, stroke, myocardial infarction or rehospitalization for heart failure.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">125</enrollment>
  <condition>Myocardial Stunning</condition>
  <arm_group>
    <arm_group_label>STEMI</arm_group_label>
    <description>Patients with ST-elevation myocardial Infarction (STEMI) (TS) who undergo urgent coronary angiography within 12 hours of symptom onset.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TS</arm_group_label>
    <description>Patients with Takotsubo Syndrome (TS) who undergo urgent coronary angiography within 12 hours ofsymptom onset.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Echocardigraphy (ECHO)</intervention_name>
    <description>Standar 12 lead electrocardiogram</description>
    <arm_group_label>STEMI</arm_group_label>
    <arm_group_label>TS</arm_group_label>
    <other_name>Standard electrocardigraphy (ECG )</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Bloodtest</intervention_name>
    <description>cardiac biomarkers</description>
    <arm_group_label>STEMI</arm_group_label>
    <arm_group_label>TS</arm_group_label>
    <other_name>Troponin and NT-proBNP</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with STEMI or TS who undergo urgent coronary angiography within 12 hours of&#xD;
        symptom onset.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  STEMI or TS with planned coronary angiography within 12 hours from the onset of&#xD;
             symptoms&#xD;
&#xD;
          -  Written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiogenic shock, defined as Killip class IV&#xD;
&#xD;
          -  Expected inability to comply with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Cardiology; Sahlgrenska University Hospital</name>
      <address>
        <city>Gothenburg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Björn Redfors, MD, PhD</last_name>
      <phone>004631-342 7560;</phone>
      <email>Bjoern.Redfors@wlab.gu.se</email>
    </contact>
    <contact_backup>
      <last_name>Sandeep Jha, MD</last_name>
      <phone>0046738491912</phone>
      <email>sandeep.jha@vgregion.se</email>
    </contact_backup>
    <investigator>
      <last_name>Björn Redfors, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sandeep Jha, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Emanuele Bobbio, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sigurdur Thorleifsson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thomas Mellberg, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rickard Zeijlon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>July 21, 2020</last_update_submitted>
  <last_update_submitted_qc>July 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vastra Gotaland Region</investigator_affiliation>
    <investigator_full_name>Björn Redfors</investigator_full_name>
    <investigator_title>Doctor of medicine, PhD; Associate Proffessor</investigator_title>
  </responsible_party>
  <keyword>Myocardial Stunning</keyword>
  <keyword>Acute heart failure</keyword>
  <keyword>Taoktsubo Syndrome</keyword>
  <keyword>Acute myocardial infarction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Myocardial Stunning</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04448639
org study id: Dnr 2019-04092
nct id: NCT04448639
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) Study

      Background: Acute myocardial stunning, herein defined as the reversible loss of myocardial
      function, occurs in both takotsubo syndrome (TS) and ST-elevation myocardial infarction
      (STEMI), and can be life-threatening in both conditions. However, despite typically having
      considerably more pronounced myocardial stunning, TS patients have better prognosis than
      patients with STEMI. Despite the different relationship between extent of myocardial stunning
      and prognosis in TS vs STEMI, no 'head-to-head' comparison of the myocardial stunning
      phenotypes in TS vs STEMI has been done.

      Methods: The Stunning In Takotsubo and Acute Myocardial Infarction (STAMI) study is a
      single-center, prospective clinical study that will enroll 100 patients with STEMI and 25
      patients with TS. Echocardiography, laboratory testing (including troponin and NTpro-BNP),
      and ECG will be done immediately after angiography and at days 1, 2, 3, 7, 14 and 30. The
      primary endpoint is the proportion of myocardial stunning that has resolved after 72 hours,
      as determined by echocardiography. Total myocardial stunning is defined as the extent of
      akinesia observed at day 0 that resolves by day 30.
Prospective assessment of the temporal electrocardiographic-, vectorcardiographic- and
      echocardiographic changes in STelevation myocardial infarction versus the takotsubo syndrome.

      AIM To compare the temporal pattern of myocardial funtional recovery after ST-elevation
      myocardial infarction (STEMI) versus the takotsubo syndrome (TS).

      BACKGROUND Modern therapies have reduced the incidence of acute ischemic heart failure (AIHF)
      -But AIHF is still common and once it develops prognosis remains dismal.Despite considerable
      therapeutic advancements over the last decades, acute myocardialinfarction (AMI) remains one
      of the most common causes of death . Among patients who are admitted with AMI, the 10% that
      develop AIHF account for approximately 50% of Deaths within 30 days . The prognosis for
      patients with AIHF has not improved over the last decade . AIHF occurs due to acute loss of
      cardiac function, some of which occurs in myocardium that is not irreparably damaged - so
      called stunned myocardium.

      Myocardial stunning in AIHF - Temporary mechanical dysfunction without irreparable injury.
      Myocardial stunning was originally described in the setting of ischemia and was defined as
      temporary mechanical dysfunction that persists after resolution of ischemia, with the absence
      of irreversible histological damage . For the purpose of this application it is more broadly
      defined as temporary mechanical dysfunction, with the absence of irreversible histological
      damage - irrespective of the underlying cause. Myocardial stunning is believed to be a
      harmful phenomenon caused by cellular injury .

      Study hypothesis: Myocardial stunning is a protective mechanism by which the cardiomyocytes
      preserve energy for vital processes in states of severe cellular stress - but that can
      "overshoot" and lead to potentially lethal cardiac decompensation. In the normal heart, the
      contractile apparatus consumes the majority of myocardial energy and oxygen . Non-contractile
      myocardial functions, including cellular and electrical homeostasis, require less than 20% as
      much oxygen. When oxygen supply to the heart is interrupted myocardial stunning ensues within
      seconds, whereas it takes at least 10 minutes for the cardiomyocyte's energy metabolites to
      decrease to 50% of their initial level .Hence, by shutting down the contractile apparatus
      before it consumes the cells' energy stores myocardial stunning effectively preserves energy
      for processes that are necessary for cell survival . Irrespective of its beneficial effects
      on cardiomyocyte metabolism, myocardial stunning may lead to sufficiently pronounced cardiac
      dysfunction to cause life-threatening AIHF.

      Study purpose:

      To better understand the difference between myocardial stunning in STEMI and the more benign
      form of stunning in TS. The sudden occurrence of temporary myocardial mechanical dysfunction
      with the absence of irreversible myocardial damage is not limited to AMI. It can occur
      postoperatively after cardiac arrest; in the settings of acute myocarditis and
      tachycardia-induced cardiomyopathy; and as a consequence of severe emotional or somatic
      stress in the takotsubo syndrome .Intriguingly, takotsubo is characterized by a compensated
      hemodynamic profile despite extensive myocardial dysfunction, effective recovery of
      myocardial function within days orweeks, and a relatively good prognosis .Takotsubo therefore
      appears to be a more efficient form of stunning than AIHF. Better understanding of the
      mechanisms behind the stunning phenomenon could allow for manipulation of the stunning
      phenotype in AIHF, or for pharmacological reversal of myocardial stunning once coronary
      reperfusion and adequate myocardial energy delivery has been ensured.
observational model: Case-Control
time perspective: Prospective
measure: Proportion of stunning that has resolved at 3 days versus 14 days
time frame: 30 days
description: StunningResolution at 3 days is defined as StunningRes3D = (%Akinesia Baseline - %Akinesia 3day) / (%Akinesia Baseline -
%Akinesia 30days); where %Akinesia is calculated as the endocardial length of the akinetic left ventricular myocardium divided by the total endocardial length of the left ventricular myoocardium - as assessed in the apical 2-chamber and 4-chamber views at end-diastole.
The recovery of stunning at 3 days is compared to the recovery of stunning at 30 days. Thus a 14 day timeframe is required.
measure: Relative increase in global longitudinal strain at 3 days vs index
time frame: 3 days
description: Global longitudinal strain as measured by speckle tracking echocardiography.
measure: Global longitudinal strain at 0, 1, 2, 3, 7, 14 and 30 days
time frame: Days 0, 1, 2, 3, 7, 14, 30 days
description: Global longitudinal strain as measured by speckle tracking echocardiography.
measure: Regional radial strain in the unaffected contralateral myocardial wall at days 0, 1, 2, 3, 7, 14 and 30
time frame: Days 0, 1, 2, 3, 7, 14 and 30
description: Radial longitudinal strain as measured by speckle tracking echocardiography.
measure: Major adverse cardiac events at 30 days and 1 year
time frame: Days 30 and 365
description: Major adverse cardiac event is defined as all-cause death, stroke, myocardial infarction or rehospitalization for heart failure.
arm group label: STEMI
description: Patients with ST-elevation myocardial Infarction (STEMI) (TS) who undergo urgent coronary angiography within 12 hours of symptom onset.
arm group label: TS
description: Patients with Takotsubo Syndrome (TS) who undergo urgent coronary angiography within 12 hours ofsymptom onset.
intervention type: Diagnostic Test
intervention name: Echocardigraphy (ECHO)
description: Standar 12 lead electrocardiogram
arm group label: STEMI
arm group label: TS
other name: Standard electrocardigraphy (ECG )
intervention type: Diagnostic Test
intervention name: Bloodtest
description: cardiac biomarkers
arm group label: STEMI
arm group label: TS
other name: Troponin and NT-proBNP
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Vastra Gotaland Region
investigator full name: Björn Redfors
investigator title: Doctor of medicine, PhD; Associate Proffessor
mesh term: Myocardial Infarction
mesh term: Myocardial Stunning
mesh term: Infarction
sharing ipd: Undecided