<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/NCT04403607</url>
  </required_header>
  <id_info>
    <org_study_id>GN20ID164</org_study_id>
    <nct_id>NCT04403607</nct_id>
  </id_info>
  <brief_title>Cardiac Imaging in SARS-CoV-2 (COVID-19)</brief_title>
  <acronym>CISCO-19</acronym>
  <official_title>Cardiovascular and Pulmonary Imaging in SARS-CoV-2: A Study of the Heart, Lungs and Wellbeing After COVID-19.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NHS Greater Glasgow and Clyde</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Glasgow</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NHS Greater Glasgow and Clyde</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>
      One-in-four patients with COVID-19 pneumonia develop life-threatening heart problems. Through&#xD;
      cardiovascular imaging and biomarkers analyses this study aims to evaluate whether COVID-19&#xD;
      infection results in heart injury. The investigators will also investigate which patients are&#xD;
      at risk of heart injury as a result of COVID-19 and why only some patients suffer heart&#xD;
      problems as a consequence of the infection. The study will also assess multisystem&#xD;
      involvement including the lungs and kidneys.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our study is supported through the Chief Scientist Office Rapid Research in Covid-19&#xD;
      (RARC-19) programme. Our study will clarify the pathogenesis of cardiopulmonary injury,&#xD;
      notably endotypes of myocardial injury including myocarditis, in patients with COVID-19.&#xD;
&#xD;
      The study involves a prospective, observational, multicentre, longitudinal cohort design.The&#xD;
      investigators aim to minimise selection bias by adopting consecutive screening of all-comers&#xD;
      hospitalised with COVID-19 and the eligibility criteria are broad. For example, severe renal&#xD;
      dysfunction is not an exclusion criterion. The sample size is 180 patients enrolled at&#xD;
      baseline with 160 attending for the primary outcome evaluation (cardiac imaging) at 28 days&#xD;
      post-discharge. The investigators will use advanced cardiovascular imaging to identify the&#xD;
      number (proportion) of patients with myocardial inflammation (myocarditis) that is&#xD;
      sub-clinical (i.e. not diagnosed) or clinically overt. Cardiovascular MRI and CT coronary&#xD;
      angiography will provide a comprehensive examination one month after discharge is intended to&#xD;
      detect persisting cardiovascular complications and diagnose clinical endotypes. The&#xD;
      investigators aim to clarify the pathological significance of serial changes in circulating&#xD;
      troponin, NTproBNP and renal function. By correlating the MRI findings with troponin I and&#xD;
      other measures of cardiovascular injury, such as NTproBNP, our results will inform care&#xD;
      pathways that use these blood tests to guide the management of patients with COVID-19.&#xD;
      Correlation of imaging findings with baseline clinical information, biomarkers, patient&#xD;
      reported outcome measures and well-being in the longer term will help to clarify the clinical&#xD;
      significance of cardiovascular complications in COVID-19. Since the design is observational,&#xD;
      an interim analysis may be undertaken with the timing informed by the enrolment rate.&#xD;
&#xD;
      Longer term follow-up will include a 5-year visit, contingent on funding and ethics approval,&#xD;
      and electronic health record linkage of vital status and episodes of NHS care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Anticipated">May 2023</completion_date>
  <primary_completion_date type="Actual">March 18, 2021</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>The primary cardiac outcome is the proportion of patients with a diagnosis of myocardial inflammation (myocarditis).</measure>
    <time_frame>28 days after discharge from hospital</time_frame>
    <description>Myocardial inflammation (or myocarditis) will be revealed by cardiovascular magnetic resonance imaging (MRI) according to contemporary guidelines including the modified Lake Louise Criteria. The endotypes of myocardial injury are 1) myocardial inflammation due to 1.1) viral myocarditis, 1.2) ischaemia, or 1.3) stress (Takotsubo) cardiomyopathy, 2) myocardial infarction, 3) indeterminate, or 4) none. The final diagnosis will be a consensus-based determination by an expert panel. This information will provide insights into the incidence, nature, time-course and clinical significance of cardiovascular involvement in patients with COVID-19. The clinical significance of our findings will be assessed through associations with patient reported outcome measures (PROMS) and health outcomes in the longer term.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The primary cardio-pulmonary outcome is the proportion of patients with thrombosis</measure>
    <time_frame>28 days after discharge from hospital</time_frame>
    <description>Thrombosis of the right heart, pulmonary arteries and left heart will be determined contrast-enhanced CT chest, angiography and MRI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Myocardial injury</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess mechanisms using circulating biomarkers of cardiac injury, high sensitivity troponin I (ng/L) and its change over time from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial stress</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess the significance of myocardial injury by measuring circulating concentrations of NTproBNP (pg/mL) and its change over time from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic inflammation</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess systemic inflammation by measurement of the peak circulating concentration of C-reactive protein (mg/dL) and its change over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular injury</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess vascular injury/inflammation by measurement of the peak circulating concentration of IL-6 (pg/mL) and its change over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial activation and haemostasis</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess endothelial injury by immunoassay measurement of the peak circulating concentration of VWF:ag (IU/dL) and its change over time. Other measures of haemostasis will also be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrin lysis</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess fibrin lysis by measurement of the peak circulating concentration of fibrin D-dimer (IU/dL) and its change over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess coagulation by measurement of Activated Partial Thromboplastin Time (APTT) in seconds. Other measures of coagulation will also be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet count</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess platelet count (n/microlitre), minimum value (thrombocytopaenia) and change over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Assess renal function using urine albumin:creatinine ratio and its change over time. Other measures of renal function/injury will also be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantify myocardial perfusion as a measure of coronary microvascular function</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Stress perfusion MRI will provide quantitative assessments of myocardial perfusion (ml/min/g) and classify perfusion abnormalities according to other MRI findings e.g. scar, inflammation and coronary artery disease as revealed by CT coronary angiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of the primary outcome according to a prior history of cardiovascular disease or no history of prior cardiovascular disease.</measure>
    <time_frame>28 days after discharge from hospital, &gt; 1 year post discharge (average 18-22 months)</time_frame>
    <description>Imaging for coronary disease, PTE and lung pathology will be correlated with NHS clinical data on prior history of cardiovascular disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcome measures (PROMS) - health status</measure>
    <time_frame>1 year</time_frame>
    <description>Health status, well being and function will be prospectively assessed using prespecified PROMS : EuroQOL EQ-5D-5L score. Other measures of health status will also be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMS - functional capacity</measure>
    <time_frame>1 year</time_frame>
    <description>Patient reported functional activity using the Duke Activity Status Index (DASI), measured by the score generated from the questionnaire (https://www.mdcalc.com/duke-activity-status-index-dasi)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cardiovascular science - vascular biology</measure>
    <time_frame>1 year</time_frame>
    <description>Exploratory study to help better understand the cardiovascular pathophysiology of COVID-19. The outcome is endothelial function in of isolated arterioles from gluteal biopsy. Endothelial function will be the (Emax, % vasorelaxation to acetylcholine in a pre-constricted arteriole). Other measures of vascular function will also be assessed.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiovascular science - mathematical modelling</measure>
    <time_frame>1 year</time_frame>
    <description>Exploratory study to help better understand the cardiac biomechanical implications of COVID-19. The outcome measure will be myocardial stiffness (Cauchy stress, kPa). The sub-studies will involve using mathematical modelling and, relatedly, statistical emulation. The models will also include the coronary/pulmonary circulation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiovascular science - pathology</measure>
    <time_frame>1 year</time_frame>
    <description>The pathogenesis of SARS-CoV-2 will be examined using histopathology techniques. The outcome is SARS-CoV-2 viral protein or RNA identified in cardiovascular cells.</description>
  </other_outcome>
  <other_outcome>
    <measure>Health outcomes (serious adverse events)</measure>
    <time_frame>20 years</time_frame>
    <description>Health outcomes as measured by the occurrence of serious adverse events (SAE) quantified by 1) rehospitalisation and 2) death. These events will be identified in the longer term using electronic record linkage to health records held by government and the National Health Service.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">180</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>COVID-19</arm_group_label>
    <description>Patients with confirmed COVID-19 meeting the eligibility criteria specified in the protocol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>COVID-19 negative. Age/sex matched to the COVID-19 cohort. Age range 40-80 years. At least one cardiovascular risk factor by ASSIGN criteria.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Samples will be stored for biomarker analyses including DNA&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All-comers who have attended or admitted to hospital for COVID-19 and meet the eligibility&#xD;
        criteria described&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History of hospital attendance or hospitalisation for COVID-19, confirmed by a&#xD;
             clinical diagnosis, laboratory test e.g. PCR and/or a radiological test e.g. CT chest&#xD;
             or chest X-ray&#xD;
&#xD;
          -  Age 18 years or more&#xD;
&#xD;
          -  Capacity to provide written informed consent&#xD;
&#xD;
          -  Able to comply with study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contra-indication to CMR e.g. severe claustrophobia, metallic foreign body&#xD;
&#xD;
          -  Lack of informed consent&#xD;
&#xD;
          -  Women who are pregnant, breast-feeding or of child-bearing potential without a&#xD;
             negative pregnancy test&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Colin Berry, MBChB/PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Glasgow / NHS Greater Glasgow &amp; Clyde</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Alexandra Hospital</name>
      <address>
        <city>Paisley</city>
        <state>Renfrewshire</state>
        <zip>PA2 9PJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G31 2ER</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>https://www.glasgowctu.org/Home</url>
    <description>Glasgow Clinical Trials Unit</description>
  </link>
  <link>
    <url>https://www.cso.scot.nhs.uk/covidcalloutcome/</url>
    <description>Chief Scientist Office, Scottish Government - Rapid Research in Covid-19 (RARC-19)</description>
  </link>
  <reference>
    <citation>Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, Madhur MS, Tomaszewski M, Maffia P, D'Acquisto F, Nicklin SA, Marian AJ, Nosalski R, Murray EC, Guzik B, Berry C, Touyz RM, Kreutz R, Wang DW, Bhella D, Sagliocco O, Crea F, Thomson EC, McInnes IB. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020 Aug 1;116(10):1666-1687. doi: 10.1093/cvr/cvaa106.</citation>
    <PMID>32352535</PMID>
  </reference>
  <reference>
    <citation>Cosyns B, Lochy S, Luchian ML, Gimelli A, Pontone G, Allard SD, de Mey J, Rosseel P, Dweck M, Petersen SE, Edvardsen T. The role of cardiovascular imaging for myocardial injury in hospitalized COVID-19 patients. Eur Heart J Cardiovasc Imaging. 2020 Jul 1;21(7):709-714. doi: 10.1093/ehjci/jeaa136.</citation>
    <PMID>32391912</PMID>
  </reference>
  <reference>
    <citation>Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Helio T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013 Sep;34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3.</citation>
    <PMID>23824828</PMID>
  </reference>
  <reference>
    <citation>Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.</citation>
    <PMID>30545455</PMID>
  </reference>
  <reference>
    <citation>Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e651. doi: 10.1161/CIR.0000000000000617. No abstract available. Erratum In: Circulation. 2018 Nov 13;138(20):e652.</citation>
    <PMID>30571511</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>March 2, 2022</last_update_submitted>
  <last_update_submitted_qc>March 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04403607
org study id: GN20ID164
nct id: NCT04403607
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
One-in-four patients with COVID-19 pneumonia develop life-threatening heart problems. Through
      cardiovascular imaging and biomarkers analyses this study aims to evaluate whether COVID-19
      infection results in heart injury. The investigators will also investigate which patients are
      at risk of heart injury as a result of COVID-19 and why only some patients suffer heart
      problems as a consequence of the infection. The study will also assess multisystem
      involvement including the lungs and kidneys.
Our study is supported through the Chief Scientist Office Rapid Research in Covid-19
      (RARC-19) programme. Our study will clarify the pathogenesis of cardiopulmonary injury,
      notably endotypes of myocardial injury including myocarditis, in patients with COVID-19.

      The study involves a prospective, observational, multicentre, longitudinal cohort design.The
      investigators aim to minimise selection bias by adopting consecutive screening of all-comers
      hospitalised with COVID-19 and the eligibility criteria are broad. For example, severe renal
      dysfunction is not an exclusion criterion. The sample size is 180 patients enrolled at
      baseline with 160 attending for the primary outcome evaluation (cardiac imaging) at 28 days
      post-discharge. The investigators will use advanced cardiovascular imaging to identify the
      number (proportion) of patients with myocardial inflammation (myocarditis) that is
      sub-clinical (i.e. not diagnosed) or clinically overt. Cardiovascular MRI and CT coronary
      angiography will provide a comprehensive examination one month after discharge is intended to
      detect persisting cardiovascular complications and diagnose clinical endotypes. The
      investigators aim to clarify the pathological significance of serial changes in circulating
      troponin, NTproBNP and renal function. By correlating the MRI findings with troponin I and
      other measures of cardiovascular injury, such as NTproBNP, our results will inform care
      pathways that use these blood tests to guide the management of patients with COVID-19.
      Correlation of imaging findings with baseline clinical information, biomarkers, patient
      reported outcome measures and well-being in the longer term will help to clarify the clinical
      significance of cardiovascular complications in COVID-19. Since the design is observational,
      an interim analysis may be undertaken with the timing informed by the enrolment rate.

      Longer term follow-up will include a 5-year visit, contingent on funding and ethics approval,
      and electronic health record linkage of vital status and episodes of NHS care.
observational model: Cohort
time perspective: Prospective
measure: The primary cardiac outcome is the proportion of patients with a diagnosis of myocardial inflammation (myocarditis).
time frame: 28 days after discharge from hospital
description: Myocardial inflammation (or myocarditis) will be revealed by cardiovascular magnetic resonance imaging (MRI) according to contemporary guidelines including the modified Lake Louise Criteria. The endotypes of myocardial injury are 1) myocardial inflammation due to 1.1) viral myocarditis, 1.2) ischaemia, or 1.3) stress (Takotsubo) cardiomyopathy, 2) myocardial infarction, 3) indeterminate, or 4) none. The final diagnosis will be a consensus-based determination by an expert panel. This information will provide insights into the incidence, nature, time-course and clinical significance of cardiovascular involvement in patients with COVID-19. The clinical significance of our findings will be assessed through associations with patient reported outcome measures (PROMS) and health outcomes in the longer term.
measure: The primary cardio-pulmonary outcome is the proportion of patients with thrombosis
time frame: 28 days after discharge from hospital
description: Thrombosis of the right heart, pulmonary arteries and left heart will be determined contrast-enhanced CT chest, angiography and MRI.
measure: Myocardial injury
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess mechanisms using circulating biomarkers of cardiac injury, high sensitivity troponin I (ng/L) and its change over time from baseline.
measure: Myocardial stress
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess the significance of myocardial injury by measuring circulating concentrations of NTproBNP (pg/mL) and its change over time from baseline.
measure: Systemic inflammation
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess systemic inflammation by measurement of the peak circulating concentration of C-reactive protein (mg/dL) and its change over time.
measure: Vascular injury
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess vascular injury/inflammation by measurement of the peak circulating concentration of IL-6 (pg/mL) and its change over time.
measure: Endothelial activation and haemostasis
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess endothelial injury by immunoassay measurement of the peak circulating concentration of VWF:ag (IU/dL) and its change over time. Other measures of haemostasis will also be measured.
measure: Fibrin lysis
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess fibrin lysis by measurement of the peak circulating concentration of fibrin D-dimer (IU/dL) and its change over time.
measure: Coagulation
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess coagulation by measurement of Activated Partial Thromboplastin Time (APTT) in seconds. Other measures of coagulation will also be measured.
measure: Platelet count
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess platelet count (n/microlitre), minimum value (thrombocytopaenia) and change over time.
measure: Renal function
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Assess renal function using urine albumin:creatinine ratio and its change over time. Other measures of renal function/injury will also be assessed.
measure: Quantify myocardial perfusion as a measure of coronary microvascular function
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Stress perfusion MRI will provide quantitative assessments of myocardial perfusion (ml/min/g) and classify perfusion abnormalities according to other MRI findings e.g. scar, inflammation and coronary artery disease as revealed by CT coronary angiography.
measure: Association of the primary outcome according to a prior history of cardiovascular disease or no history of prior cardiovascular disease.
time frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
description: Imaging for coronary disease, PTE and lung pathology will be correlated with NHS clinical data on prior history of cardiovascular disease.
measure: Patient reported outcome measures (PROMS) - health status
time frame: 1 year
description: Health status, well being and function will be prospectively assessed using prespecified PROMS : EuroQOL EQ-5D-5L score. Other measures of health status will also be assessed.
measure: PROMS - functional capacity
time frame: 1 year
description: Patient reported functional activity using the Duke Activity Status Index (DASI), measured by the score generated from the questionnaire (https://www.mdcalc.com/duke-activity-status-index-dasi)
measure: Cardiovascular science - vascular biology
time frame: 1 year
description: Exploratory study to help better understand the cardiovascular pathophysiology of COVID-19. The outcome is endothelial function in of isolated arterioles from gluteal biopsy. Endothelial function will be the (Emax, % vasorelaxation to acetylcholine in a pre-constricted arteriole). Other measures of vascular function will also be assessed.
measure: Cardiovascular science - mathematical modelling
time frame: 1 year
description: Exploratory study to help better understand the cardiac biomechanical implications of COVID-19. The outcome measure will be myocardial stiffness (Cauchy stress, kPa). The sub-studies will involve using mathematical modelling and, relatedly, statistical emulation. The models will also include the coronary/pulmonary circulation.
measure: Cardiovascular science - pathology
time frame: 1 year
description: The pathogenesis of SARS-CoV-2 will be examined using histopathology techniques. The outcome is SARS-CoV-2 viral protein or RNA identified in cardiovascular cells.
measure: Health outcomes (serious adverse events)
time frame: 20 years
description: Health outcomes as measured by the occurrence of serious adverse events (SAE) quantified by 1) rehospitalisation and 2) death. These events will be identified in the longer term using electronic record linkage to health records held by government and the National Health Service.
arm group label: COVID-19
description: Patients with confirmed COVID-19 meeting the eligibility criteria specified in the protocol.
arm group label: Control
description: COVID-19 negative. Age/sex matched to the COVID-19 cohort. Age range 40-80 years. At least one cardiovascular risk factor by ASSIGN criteria.
Samples will be stored for biomarker analyses including DNA
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Colin Berry, MBChB/PhD
role: Principal Investigator
affiliation: University of Glasgow / NHS Greater Glasgow & Clyde
facility: 
facility: 
facility: 
country: United Kingdom
url: https://www.glasgowctu.org/Home
description: Glasgow Clinical Trials Unit
url: https://www.cso.scot.nhs.uk/covidcalloutcome/
description: Chief Scientist Office, Scottish Government - Rapid Research in Covid-19 (RARC-19)
citation: Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, Madhur MS, Tomaszewski M, Maffia P, D'Acquisto F, Nicklin SA, Marian AJ, Nosalski R, Murray EC, Guzik B, Berry C, Touyz RM, Kreutz R, Wang DW, Bhella D, Sagliocco O, Crea F, Thomson EC, McInnes IB. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020 Aug 1;116(10):1666-1687. doi: 10.1093/cvr/cvaa106.
PMID: 32352535
citation: Cosyns B, Lochy S, Luchian ML, Gimelli A, Pontone G, Allard SD, de Mey J, Rosseel P, Dweck M, Petersen SE, Edvardsen T. The role of cardiovascular imaging for myocardial injury in hospitalized COVID-19 patients. Eur Heart J Cardiovasc Imaging. 2020 Jul 1;21(7):709-714. doi: 10.1093/ehjci/jeaa136.
PMID: 32391912
citation: Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Helio T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013 Sep;34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3.
PMID: 23824828
citation: Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.
PMID: 30545455
citation: Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e651. doi: 10.1161/CIR.0000000000000617. No abstract available. Erratum In: Circulation. 2018 Nov 13;138(20):e652.
PMID: 30571511
responsible party type: Sponsor