<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/NCT04412369</url>
  </required_header>
  <id_info>
    <org_study_id>A09565</org_study_id>
    <nct_id>NCT04412369</nct_id>
  </id_info>
  <brief_title>Multi-modality Imaging &amp; Immunophenotyping of COVID-19 Related Myocardial Injury</brief_title>
  <acronym>MIIC-MI</acronym>
  <official_title>Multi-modality Imaging &amp; Immunophenotyping of COVID-19 Related Myocardial Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cambridge</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>British Heart Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cambridge</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>
      Cardiovascular involvement in coronavirus disease-2019 (COVID-19) encompasses a wide range of&#xD;
      vascular and myocardial pathologies, including both acute and long-term sequelae. The MIIC-MI&#xD;
      study aims to investigate mechanisms of cardiac injury in COVID-19 using multi-modality&#xD;
      imaging and immunophenotyping to better understand the link with adverse patient outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiovascular involvement in coronavirus disease-2019 (COVID-19) encompasses a wide range of&#xD;
      vascular and myocardial pathologies, including both acute and long-term sequelae.&#xD;
&#xD;
      Cardiac Troponin elevation, a marker of acute myocardial injury, has been identified in up to&#xD;
      28% of hospitalized patients with coronavirus disease 2019 (COVID-19) and is associated with&#xD;
      an increased mortality risk. However, the predominant aetiology of myocardial injury relating&#xD;
      to COVID-19 remains unclear. The Troponin leak could either signify direct cardiac&#xD;
      involvement in COVID-19 or serve as a non-specific marker of a severe systemic insult.&#xD;
&#xD;
      There have been numerous reports of acute myocarditis in patients with COVID-19. Other&#xD;
      contributory mechanisms of cardiac Troponin elevation in patients with COVID-19 that are also&#xD;
      driven by a proinflammatory state include acute myocardial infarction due to atherosclerotic&#xD;
      plaque rupture (type 1) or demand ischemia (type 2), endothelial and microvascular&#xD;
      dysfunction, immune-mediated activation of coagulation and fibrinolytic systems, and stress&#xD;
      cardiomyopathy.&#xD;
&#xD;
      Longer-term effects of COVID-19 on the cardiovascular system are also unknown. Many&#xD;
      individuals with post-acute sequalae of SARS-CoV-2 infection (or 'long COVID') have&#xD;
      unexplained cardiac symptoms. Patients may also present with new-onset heart failure after&#xD;
      COVID-19, which is not attributed to another cause.&#xD;
&#xD;
      We aim to identify patterns of myocardial injury in COVID-19 using non-invasive&#xD;
      multi-modality cardiac imaging, paired with cytokine/chemokine testing, immunophenotyping of&#xD;
      peripheral blood cells and coagulation profiles.&#xD;
&#xD;
      A better understanding of the mechanisms underlying the excess mortality risk attributable to&#xD;
      myocardial injury in COVID-19 is needed and may help to improve patient care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Actual">December 1, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnosis</measure>
    <time_frame>Baseline</time_frame>
    <description>Number of participants with a diagnosis of COVID-19 related myocarditis, Type 1 or 2 myocardial infarction and/or other mechanism of cardiac injury confirmed by multi-modality imaging.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune markers</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of a panel of inflammatory cytokines and immune cell profiles in patients stratified by cardiac diagnosis/imaging findings</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation markers</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of a panel of blood coagulation markers in patients stratified by cardiac diagnosis/imaging findings</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>COVID19</condition>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Study group</arm_group_label>
    <description>Patients with COVID-19 and cardiac Troponin elevation</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Non-invasive cardiac imaging</intervention_name>
    <description>Cardiac MRI ± CT coronary angiography ± Cardiac PET/MRI (68Ga-DOTATATE or 18F-FDG)</description>
    <arm_group_label>Study group</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 with a history of COVID-19 and cardiovascular involvement&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt;18 years old&#xD;
&#xD;
          -  Confirmed COVID-19 infection AND Troponin I elevation &gt;99th percentile of upper&#xD;
             reference limit OR new-onset heart failure OR unexplained cardiac symptoms&#xD;
&#xD;
          -  Able to give written, informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women of child-bearing potential not using adequate contraception&#xD;
&#xD;
          -  Contra-indication to MRI scanning&#xD;
&#xD;
          -  Contrast allergy or contrast-nephropathy&#xD;
&#xD;
          -  Chronic kidney disease (eGFR &lt;30 mL/min/1.73 m2)&#xD;
&#xD;
          -  Previous myocardial infarction&#xD;
&#xD;
          -  Uncontrolled atrial fibrillation&#xD;
&#xD;
          -  Uncontrolled chronic inflammatory disease&#xD;
&#xD;
          -  Severe lymphopenia (&lt;0.2 x109/L)&#xD;
&#xD;
          -  Treatment with immunomodulatory therapies within the last month (excluding inhaled or&#xD;
             topical steroid therapy)&#xD;
&#xD;
          -  Any medical condition, in the opinion of the investigator, that prevents the&#xD;
             participant from lying flat during scanning, or from participating in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason M Tarkin, MBBS, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cambridge Univeristy Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>March 26, 2023</last_update_submitted>
  <last_update_submitted_qc>March 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cambridge</investigator_affiliation>
    <investigator_full_name>Jason Tarkin</investigator_full_name>
    <investigator_title>Wellcome Clinical Research Career Development Fellow</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Cardiovascular Diseases</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/NCT04412369
org study id: A09565
nct id: NCT04412369
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cardiovascular involvement in coronavirus disease-2019 (COVID-19) encompasses a wide range of
      vascular and myocardial pathologies, including both acute and long-term sequelae. The MIIC-MI
      study aims to investigate mechanisms of cardiac injury in COVID-19 using multi-modality
      imaging and immunophenotyping to better understand the link with adverse patient outcomes.
Cardiovascular involvement in coronavirus disease-2019 (COVID-19) encompasses a wide range of
      vascular and myocardial pathologies, including both acute and long-term sequelae.

      Cardiac Troponin elevation, a marker of acute myocardial injury, has been identified in up to
      28% of hospitalized patients with coronavirus disease 2019 (COVID-19) and is associated with
      an increased mortality risk. However, the predominant aetiology of myocardial injury relating
      to COVID-19 remains unclear. The Troponin leak could either signify direct cardiac
      involvement in COVID-19 or serve as a non-specific marker of a severe systemic insult.

      There have been numerous reports of acute myocarditis in patients with COVID-19. Other
      contributory mechanisms of cardiac Troponin elevation in patients with COVID-19 that are also
      driven by a proinflammatory state include acute myocardial infarction due to atherosclerotic
      plaque rupture (type 1) or demand ischemia (type 2), endothelial and microvascular
      dysfunction, immune-mediated activation of coagulation and fibrinolytic systems, and stress
      cardiomyopathy.

      Longer-term effects of COVID-19 on the cardiovascular system are also unknown. Many
      individuals with post-acute sequalae of SARS-CoV-2 infection (or 'long COVID') have
      unexplained cardiac symptoms. Patients may also present with new-onset heart failure after
      COVID-19, which is not attributed to another cause.

      We aim to identify patterns of myocardial injury in COVID-19 using non-invasive
      multi-modality cardiac imaging, paired with cytokine/chemokine testing, immunophenotyping of
      peripheral blood cells and coagulation profiles.

      A better understanding of the mechanisms underlying the excess mortality risk attributable to
      myocardial injury in COVID-19 is needed and may help to improve patient care.
observational model: Case-Only
time perspective: Prospective
measure: Diagnosis
time frame: Baseline
description: Number of participants with a diagnosis of COVID-19 related myocarditis, Type 1 or 2 myocardial infarction and/or other mechanism of cardiac injury confirmed by multi-modality imaging.
measure: Immune markers
time frame: Baseline
description: Comparison of a panel of inflammatory cytokines and immune cell profiles in patients stratified by cardiac diagnosis/imaging findings
measure: Coagulation markers
time frame: Baseline
description: Comparison of a panel of blood coagulation markers in patients stratified by cardiac diagnosis/imaging findings
arm group label: Study group
description: Patients with COVID-19 and cardiac Troponin elevation
intervention type: Diagnostic Test
intervention name: Non-invasive cardiac imaging
description: Cardiac MRI ± CT coronary angiography ± Cardiac PET/MRI (68Ga-DOTATATE or 18F-FDG)
arm group label: Study group
Blood samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Jason M Tarkin, MBBS, PhD
role: Principal Investigator
affiliation: University of Cambridge
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Cambridge
investigator full name: Jason Tarkin
investigator title: Wellcome Clinical Research Career Development Fellow
mesh term: COVID-19
mesh term: Cardiovascular Diseases
sharing ipd: Undecided