<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/NCT04493307</url>
  </required_header>
  <id_info>
    <org_study_id>1602903</org_study_id>
    <nct_id>NCT04493307</nct_id>
  </id_info>
  <brief_title>The Evaluation of Hemostasis in Hospitalized COVID-19 Patients</brief_title>
  <acronym>TARGET-COVID</acronym>
  <official_title>The Evaluation of Hemostasis by Thromboelastography, Platelet Function Testing, and Biomarker Analysis in Hospitalized COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LifeBridge Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Haemonetics Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Inflammatory Markers Laboratory</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chronolog Corporation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Precision Biologics, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>LifeBridge Health</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>
      Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute&#xD;
      respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to predispose patients to&#xD;
      thrombotic diseases (venous and arterial) with reported rates in hospitalized patients&#xD;
      between 17-40%. The influence of SARS-CoV-2 infection on the coagulation is hypothesized to&#xD;
      be regulated by platelet activation, proinflammatory cytokines, endothelial cell injury and&#xD;
      stasis. The elevated levels of d-dimer and fibrinogen and clinical signs of organ damage&#xD;
      point to a significant hypercoagulable state. The latter induces a high risk for&#xD;
      micro-thrombi and multi-organ ischemia. Therefore, early detection and a comprehensive&#xD;
      understanding of the influence of the virus on the coagulation and platelet pathways are&#xD;
      essential to address this epidemic. It is critical at this time to make all efforts possible&#xD;
      to optimize our available technology to care for COVID-19 patients who are at risk for&#xD;
      thrombotic disease through appropriate choice, dosing, and laboratory monitoring of&#xD;
      antithrombotic therapy.&#xD;
&#xD;
      The investigators hypothesize that COVID-19 is a heightened prothrombotic/hypercoagulability&#xD;
      state that can be characterized using platelet function testing and thrombelastography. More&#xD;
      information is required to study the effect of COVID-19 on coagulation and platelet pathways&#xD;
      to develop effective antithrombotic treatment strategies.&#xD;
&#xD;
      This is a multi-center center, non-interventional study enrolling patients who are COVID-19&#xD;
      positive or who have tested negative showing indication of the disease (high D-dimer and&#xD;
      positive lung imaging). The study specific laboratory assessments will be obtained at&#xD;
      baseline (closest to time of hospitalization), Day 3, and Day 8 from baseline and at hospital&#xD;
      discharge. Laboratory measurements for TEG 6S , platelet aggregation, T-TAS, urinary&#xD;
      thromboxane, genotyping, serum and plasma biomarkers will be analyzed . In-hospital and&#xD;
      clinical follow-up data will be entered into a COVID registry Patients will be followed for&#xD;
      clinical events during hospitalization, and up to 6 months after discharge.&#xD;
&#xD;
      Patients (n=100) hospitalized with at least one of the following will be enrolled.&#xD;
&#xD;
        1. With a confirmed diagnosis of COVID-19 infection using a positive RT- PCR or a positive&#xD;
           IgG antibody test prior to or during hospitalization or&#xD;
&#xD;
        2. With a negative COVID-19 RT-PCR test but with symptoms of possible&#xD;
&#xD;
      COVID-19 infection and:&#xD;
&#xD;
        1. an elevated D-dimer and/or&#xD;
&#xD;
        2. positive imaging results showing unilateral or bilateral pneumonia or ground-glass&#xD;
           opacity in lungs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators hypothesize that serial evaluation of (a) intrinsic thrombogenicity&#xD;
      measured by thromboelastography (b) platelet activation and aggregation, and (c) selected&#xD;
      biomarkers will provide the &quot;blueprint&quot; of individual hemostasis to precisely characterize&#xD;
      COVID-19 patients who are at heightened risk for thrombosis or bleeding. The latter will&#xD;
      facilitate future efforts to personalize antithrombotic therapy regimens in COVID-19&#xD;
      patients.&#xD;
&#xD;
      Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute&#xD;
      respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to predispose patients to&#xD;
      thrombotic diseases (venous and arterial) with reported rates in hospitalized patients&#xD;
      between 17- 40%. The influence of SARS-CoV-2 infection on the coagulation is hypothesized to&#xD;
      be regulated by platelet activation, proinflammatory cytokines, endothelial cell injury and&#xD;
      stasis.&#xD;
&#xD;
      The elevated levels of d-dimer and fibrinogen and clinical signs of organ damage point to a&#xD;
      significant hypercoagulable state. The latter induces a high risk for micro-thrombi and&#xD;
      multiorgan ischemia. Therefore, early detection and a comprehensive understanding of the&#xD;
      influence of the virus on the coagulation and platelet pathways are essential to address this&#xD;
      epidemic. It is critical at this time to make all efforts possible to optimize our available&#xD;
      technology to care for COVID-19 patients who are at risk for thrombotic disease through&#xD;
      appropriate choice, dosing, and laboratory monitoring of antithrombotic therapy.&#xD;
&#xD;
      Our research group and others have reported a &quot;thrombo-inflammatory&quot; state-a distinct&#xD;
      pathophysiological state -of heightened platelet function, hypercoagulability, and&#xD;
      inflammation in several cardiovascular disease (CVD) processes. It has been demonstrated that&#xD;
      patients with acute respiratory infections are at elevated risk for acute myocardial&#xD;
      infarction after influenza (incidence ratio [IR] 6.1, 95% CI 3.9-9.5) and after non-influenza&#xD;
      viral illnesses including other coronavirus species (IR 2.8, 95% CI 1.2-6.2). Tantry et al.&#xD;
      proposed a mechanistic link between inflammation and heightened thrombogenicity in the&#xD;
      presence of unstable CVD state. Furthermore, investigators have hypothesized that this&#xD;
      thrombo-inflammatory state becomes even more relevant when patients with CVD and human&#xD;
      immunodeficiency virus (HIV) infection undergo percutaneous coronary intervention (PCI).A&#xD;
      similar scenario may be present during COVID-19 infection, where evidence of an early&#xD;
      myonecrosis may be related to fundamental changes in pathways affecting thrombosis. However,&#xD;
      currently, there is no information on how COVID-19 influences hemostasis/thrombosis pathways&#xD;
      and subsequent adverse clinical event occurrences.&#xD;
&#xD;
      Cardiovascular comorbidities including hypertension, obesity, high cholesterol, and diabetes&#xD;
      mellitus are common in patients with COVID-19 and such patients are at higher risk for&#xD;
      morbidity and mortality.12 Furthermore, emerging demographic data in COVID-19 patients shows&#xD;
      that incidence and mortality is disproportionately higher in African Americans and Latinos.&#xD;
      In a study conducted at Sinai hospital, Lev et al. analyzed a large cohort of racially&#xD;
      diverse patients (n=1,172) with CAD or CV risk and demonstrated that sex and race are&#xD;
      significantly associated with platelet-fibrin clot strength, a marker of hypercoagulability.&#xD;
      Most interesting, AA women had the highest thrombogenicity profile, potentially conferring a&#xD;
      highrisk phenotype for thrombotic event occurrence. Furthermore, in a study entitled,&#xD;
      &quot;PlateletReactivity in Different Ethnicities&quot; also conducted at Sinai hospital, investigators&#xD;
      have demonstrated that Latino and AA races had the highest platelet-fibrin clot strength as&#xD;
      compared to Caucasians and others races studied.The latter findings may be described by&#xD;
      difference in frequency of a single-nucleotide variant in protease-activated receptor-4&#xD;
      (PAR-4) between AA and Caucasians respectively (63% vs 19%). PAR-4 is an active thrombin&#xD;
      receptor on human platelets essential for thrombin-induced platelet activation and has been&#xD;
      shown to be more active in African Americans as compared to Caucasians. This evidence may&#xD;
      provide a potential mechanistic explanation for racial disparities observed in COVID-19&#xD;
      patients and require further investigation. Hence, investigators will collect a genetic&#xD;
      sample to analyze single-nucleotide variant of PAR-4 and other genetic markers related to&#xD;
      thrombosis.&#xD;
&#xD;
      Thromboelastography (TEG) is a method for measuring global hemostasis and has been widely&#xD;
      used in surgery and anesthesiology, emergency departments, trauma centers, intensive care&#xD;
      units,and cardiac catheterization labs for transfusion management, prediction of thrombotic&#xD;
      and bleeding events, and choice/adjustment of anticoagulation and antiplatelet therapies.&#xD;
      Light transmittance aggregometry (LTA) is a widely used gold standard method for identifying&#xD;
      heightened platelet reactivity to various agonists, a marker of thrombotic risk.More common&#xD;
      conventional coagulation tests include prothrombin time (PT, INR), partial thromboplastin&#xD;
      time (aPTT), fibrinogen, platelet count, and d-dimer. However, these latter tests do not&#xD;
      reflect interactions between platelets, endothelium, and fibrinolytic factors and must be&#xD;
      used in combination to provide a complete picture of hemostasis status. Unlike these tests,&#xD;
      the TEG can assess platelet function, clot strength, and fibrinolysis. Furthermore, The TEG6s&#xD;
      Hemostasis Analyzer is a portable, all-in-one cartridge-based system that requires minimal&#xD;
      blood sample and minimal sample processing, a potential safety advantage when processing&#xD;
      blood samples in COVID-19 patients. Lastly, COVID-19 infection may be associated with acute&#xD;
      cardiac injury as indicated by elevation of cardiac biomarkers to &gt; 99th percentile of the&#xD;
      upper reference limit, but also electrocardiographic and echocardiographic abnormalities.&#xD;
      Cardiac injury is highly prevalent in patients with COVID-19 but may not be an important&#xD;
      marker as it occurs after damage has been done. Inosine and hypoxanthine are specific markers&#xD;
      of acute cardiac ischemia (ACI) that are measurable within 20 minutes as compared to 4 hours&#xD;
      with CKMB and Troponin testing. Investigators believe that this marker may indicate the early&#xD;
      presence of micro-thrombi and organ damage. Investigators plan to investigate these novel&#xD;
      markers in this trial. Investigators hypothesize that COVID-19 is a heightened&#xD;
      prothrombotic/hypercoagulability state that can be characterized using platelet function&#xD;
      testing and Thromboelastography. More information is required to study the effect of COVID-19&#xD;
      on coagulation and platelet pathways to develop effective antithrombotic treatment&#xD;
      strategies.&#xD;
&#xD;
      The study is a multi-center, non-interventional study involving laboratory testing of blood&#xD;
      samples and data collection for a COVID registry using electronic medical records. The study&#xD;
      specific laboratory assessments will be obtained at baseline (closest to time of&#xD;
      hospitalization), Day 3 and Day 8 from baseline, and at hospital discharge. Patients will be&#xD;
      followed for clinical events during hospitalization, and 1 and 6 months after discharge.&#xD;
      Patients (n=100) hospitalized at Sinai Hospital of Baltimore and Northwest Hospital with at&#xD;
      least one of the following will be enrolled.&#xD;
&#xD;
        1. With a confirmed diagnosis of COVID-19 infection using a positive RT-PCR or a positive&#xD;
           IgG antibody test prior to or during hospitalization or,&#xD;
&#xD;
        2. With a negative COVID-19 RT-PCR test but with symptoms of possible COVID-19infection&#xD;
           and:&#xD;
&#xD;
             1. an elevated D-dimer and/or&#xD;
&#xD;
             2. positive imaging results showing unilateral or bilateral pneumonia or ground glass&#xD;
                opacity in lungs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Anticipated">June 2021</completion_date>
  <primary_completion_date type="Anticipated">February 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of Hypercoagulability as measured by thromboelastography measured by TEG and platelet aggregation.</measure>
    <time_frame>up to day 8</time_frame>
    <description>Frequency of Hypercoagulability as measured by point-of-care thromboelastography (TEG6s)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of High Platelet Reactivity (HPR)</measure>
    <time_frame>up to day 8</time_frame>
    <description>Incidence of High Platelet Reactivity as measured by platelet aggregation and TEG6s</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of thrombo-inflammatory syndrome</measure>
    <time_frame>up to day 8</time_frame>
    <description>Frequency of thrombo -inflammatory syndrome as determined by D-Dimer and TEG6s</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between TEG6s parameters and clinical outcomes</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>Correlation between TEG6s parameters and clinical outcomes (thrombotic and bleeding events, need for ventilation, death)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between HPR and clinical outcomes</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>Correlation between HPR and clinical outcomes (thrombotic and bleeding events, need for ventilation, death)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine response to anticoagulation therapy</measure>
    <time_frame>up to day 8</time_frame>
    <description>Determine response to anticoagulation therapy by calculating change in R-value (CK -CKH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine level of platelet aggregation</measure>
    <time_frame>up to day 8</time_frame>
    <description>Determine level of platelet aggregation by impedance aggregometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine level of platelet aggregation</measure>
    <time_frame>up to day 8</time_frame>
    <description>Determine percent platelet aggregation by TEG-6S platelet Mapping assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine platelet thrombi and fibrin rich platelet thrombus Area Under the Curve</measure>
    <time_frame>up to day 8</time_frame>
    <description>Determine platelet thrombi and fibrin rich platelet thrombus Area Under the Curve using TTAS analyzer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine short and long IgG, IgM and IgG antibody levels</measure>
    <time_frame>up to day 6 months</time_frame>
    <description>Determine short and long IgG, IgM and IgG antibody levels against using multiple specimen types (saliva, whole blood, serum, plasma, urine)</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>COVID-19</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Phlebotomy</intervention_name>
    <description>Serial assessment of hemostasis by blood and urine collection</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and urine samples will be collected at study timepoints for the following:&#xD;
&#xD;
        1. TEG6S with citrated multi-channel and Platelet Mapping cartridges&#xD;
&#xD;
        2. Platelet aggregation will be assessed using a Chronolog Lumi- Aggregometer&#xD;
&#xD;
        3. Serum and Plasma Biomarkers of Inflammation/Cytokine Storm, Coagulation,and&#xD;
           Ischemia/Organ Injury&#xD;
&#xD;
        4. Urinary 11-dehydrothromboxane B2&#xD;
&#xD;
        5. Evaluation of whole blood thrombogenicity using The Total Thrombus- Formation Analysis&#xD;
           System (T-TAS)&#xD;
&#xD;
        6. Genotyping: Genetic variations of single nucleotide polymorphisms (SNPs) related to&#xD;
           coagulation, platelet function, immune response and thrombosis related clinical outcomes&#xD;
           using SNP microarrays and PCR-based methods.&#xD;
&#xD;
        7. COVID-19 Antibody Detection&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study's intended population is inclusive of both genders (males and females), aged 3&#xD;
        years and older, and all racial and ethnic groups.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  · Confirmed diagnosis of COVID-19 infection using a positive RT-PCR or a positive IgG&#xD;
             antibody test prior to or during hospitalization or,&#xD;
&#xD;
             · With a negative COVID-19 RT-PCR test but with symptoms of possible COVID-19&#xD;
             infection and:&#xD;
&#xD;
          -  elevated D-dimer and/or&#xD;
&#xD;
          -  positive imaging results showing unilateral or bilateral pneumonia or ground-glass&#xD;
             opacity in lungs · The subject or legal authorized representative able to read and&#xD;
             sign an informed consent document including authorization permitting release of&#xD;
             personal health information approved by the investigator's Institutional Review Board&#xD;
             (IRB).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects will be excluded from entry if ANY of the criteria listed below are met:&#xD;
&#xD;
          -  Less than 3 years of age&#xD;
&#xD;
          -  Subject is pregnant&#xD;
&#xD;
          -  Active treatment for cancer&#xD;
&#xD;
          -  History of long-term use of immunosuppressive agents&#xD;
&#xD;
          -  History of severe chronic respiratory disease and requirement for long-term oxygen&#xD;
             therapy&#xD;
&#xD;
          -  Patients undergoing hemodialysis or peritoneal dialysis&#xD;
&#xD;
          -  Patients on full dose anticoagulant at the time of enrollment&#xD;
&#xD;
          -  Any condition unsuitable for the study as determined by investigators&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul A Gurbel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LifeBridge Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>kevin bliden, MBA</last_name>
    <phone>4432441497</phone>
    <email>kbliden@lifebridgehealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cescelle Barbour, MSN</last_name>
    <phone>4106014194</phone>
    <email>cbarbour@lifebridgehealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sinai Center for Thrombosis Research</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kevin P Bliden, B.S. MBA</last_name>
      <phone>443-244-1497</phone>
      <email>kbliden@lifebridgehealth.org</email>
    </contact>
    <contact_backup>
      <last_name>Cescelle B Barbour, MSN</last_name>
      <phone>4106014194</phone>
      <email>cbarbour@lifebridgehealth.org</email>
    </contact_backup>
    <investigator>
      <last_name>Paul A Gurbel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jaime Barnes, DO</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ashwin Dharmadhikari, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04493307
org study id: 1602903
nct id: NCT04493307
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to predispose patients to
      thrombotic diseases (venous and arterial) with reported rates in hospitalized patients
      between 17-40%. The influence of SARS-CoV-2 infection on the coagulation is hypothesized to
      be regulated by platelet activation, proinflammatory cytokines, endothelial cell injury and
      stasis. The elevated levels of d-dimer and fibrinogen and clinical signs of organ damage
      point to a significant hypercoagulable state. The latter induces a high risk for
      micro-thrombi and multi-organ ischemia. Therefore, early detection and a comprehensive
      understanding of the influence of the virus on the coagulation and platelet pathways are
      essential to address this epidemic. It is critical at this time to make all efforts possible
      to optimize our available technology to care for COVID-19 patients who are at risk for
      thrombotic disease through appropriate choice, dosing, and laboratory monitoring of
      antithrombotic therapy.

      The investigators hypothesize that COVID-19 is a heightened prothrombotic/hypercoagulability
      state that can be characterized using platelet function testing and thrombelastography. More
      information is required to study the effect of COVID-19 on coagulation and platelet pathways
      to develop effective antithrombotic treatment strategies.

      This is a multi-center center, non-interventional study enrolling patients who are COVID-19
      positive or who have tested negative showing indication of the disease (high D-dimer and
      positive lung imaging). The study specific laboratory assessments will be obtained at
      baseline (closest to time of hospitalization), Day 3, and Day 8 from baseline and at hospital
      discharge. Laboratory measurements for TEG 6S , platelet aggregation, T-TAS, urinary
      thromboxane, genotyping, serum and plasma biomarkers will be analyzed . In-hospital and
      clinical follow-up data will be entered into a COVID registry Patients will be followed for
      clinical events during hospitalization, and up to 6 months after discharge.

      Patients (n=100) hospitalized with at least one of the following will be enrolled.

        1. With a confirmed diagnosis of COVID-19 infection using a positive RT- PCR or a positive
           IgG antibody test prior to or during hospitalization or

        2. With a negative COVID-19 RT-PCR test but with symptoms of possible

      COVID-19 infection and:

        1. an elevated D-dimer and/or

        2. positive imaging results showing unilateral or bilateral pneumonia or ground-glass
           opacity in lungs.
The investigators hypothesize that serial evaluation of (a) intrinsic thrombogenicity
      measured by thromboelastography (b) platelet activation and aggregation, and (c) selected
      biomarkers will provide the "blueprint" of individual hemostasis to precisely characterize
      COVID-19 patients who are at heightened risk for thrombosis or bleeding. The latter will
      facilitate future efforts to personalize antithrombotic therapy regimens in COVID-19
      patients.

      Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to predispose patients to
      thrombotic diseases (venous and arterial) with reported rates in hospitalized patients
      between 17- 40%. The influence of SARS-CoV-2 infection on the coagulation is hypothesized to
      be regulated by platelet activation, proinflammatory cytokines, endothelial cell injury and
      stasis.

      The elevated levels of d-dimer and fibrinogen and clinical signs of organ damage point to a
      significant hypercoagulable state. The latter induces a high risk for micro-thrombi and
      multiorgan ischemia. Therefore, early detection and a comprehensive understanding of the
      influence of the virus on the coagulation and platelet pathways are essential to address this
      epidemic. It is critical at this time to make all efforts possible to optimize our available
      technology to care for COVID-19 patients who are at risk for thrombotic disease through
      appropriate choice, dosing, and laboratory monitoring of antithrombotic therapy.

      Our research group and others have reported a "thrombo-inflammatory" state-a distinct
      pathophysiological state -of heightened platelet function, hypercoagulability, and
      inflammation in several cardiovascular disease (CVD) processes. It has been demonstrated that
      patients with acute respiratory infections are at elevated risk for acute myocardial
      infarction after influenza (incidence ratio [IR] 6.1, 95% CI 3.9-9.5) and after non-influenza
      viral illnesses including other coronavirus species (IR 2.8, 95% CI 1.2-6.2). Tantry et al.
      proposed a mechanistic link between inflammation and heightened thrombogenicity in the
      presence of unstable CVD state. Furthermore, investigators have hypothesized that this
      thrombo-inflammatory state becomes even more relevant when patients with CVD and human
      immunodeficiency virus (HIV) infection undergo percutaneous coronary intervention (PCI).A
      similar scenario may be present during COVID-19 infection, where evidence of an early
      myonecrosis may be related to fundamental changes in pathways affecting thrombosis. However,
      currently, there is no information on how COVID-19 influences hemostasis/thrombosis pathways
      and subsequent adverse clinical event occurrences.

      Cardiovascular comorbidities including hypertension, obesity, high cholesterol, and diabetes
      mellitus are common in patients with COVID-19 and such patients are at higher risk for
      morbidity and mortality.12 Furthermore, emerging demographic data in COVID-19 patients shows
      that incidence and mortality is disproportionately higher in African Americans and Latinos.
      In a study conducted at Sinai hospital, Lev et al. analyzed a large cohort of racially
      diverse patients (n=1,172) with CAD or CV risk and demonstrated that sex and race are
      significantly associated with platelet-fibrin clot strength, a marker of hypercoagulability.
      Most interesting, AA women had the highest thrombogenicity profile, potentially conferring a
      highrisk phenotype for thrombotic event occurrence. Furthermore, in a study entitled,
      "PlateletReactivity in Different Ethnicities" also conducted at Sinai hospital, investigators
      have demonstrated that Latino and AA races had the highest platelet-fibrin clot strength as
      compared to Caucasians and others races studied.The latter findings may be described by
      difference in frequency of a single-nucleotide variant in protease-activated receptor-4
      (PAR-4) between AA and Caucasians respectively (63% vs 19%). PAR-4 is an active thrombin
      receptor on human platelets essential for thrombin-induced platelet activation and has been
      shown to be more active in African Americans as compared to Caucasians. This evidence may
      provide a potential mechanistic explanation for racial disparities observed in COVID-19
      patients and require further investigation. Hence, investigators will collect a genetic
      sample to analyze single-nucleotide variant of PAR-4 and other genetic markers related to
      thrombosis.

      Thromboelastography (TEG) is a method for measuring global hemostasis and has been widely
      used in surgery and anesthesiology, emergency departments, trauma centers, intensive care
      units,and cardiac catheterization labs for transfusion management, prediction of thrombotic
      and bleeding events, and choice/adjustment of anticoagulation and antiplatelet therapies.
      Light transmittance aggregometry (LTA) is a widely used gold standard method for identifying
      heightened platelet reactivity to various agonists, a marker of thrombotic risk.More common
      conventional coagulation tests include prothrombin time (PT, INR), partial thromboplastin
      time (aPTT), fibrinogen, platelet count, and d-dimer. However, these latter tests do not
      reflect interactions between platelets, endothelium, and fibrinolytic factors and must be
      used in combination to provide a complete picture of hemostasis status. Unlike these tests,
      the TEG can assess platelet function, clot strength, and fibrinolysis. Furthermore, The TEG6s
      Hemostasis Analyzer is a portable, all-in-one cartridge-based system that requires minimal
      blood sample and minimal sample processing, a potential safety advantage when processing
      blood samples in COVID-19 patients. Lastly, COVID-19 infection may be associated with acute
      cardiac injury as indicated by elevation of cardiac biomarkers to > 99th percentile of the
      upper reference limit, but also electrocardiographic and echocardiographic abnormalities.
      Cardiac injury is highly prevalent in patients with COVID-19 but may not be an important
      marker as it occurs after damage has been done. Inosine and hypoxanthine are specific markers
      of acute cardiac ischemia (ACI) that are measurable within 20 minutes as compared to 4 hours
      with CKMB and Troponin testing. Investigators believe that this marker may indicate the early
      presence of micro-thrombi and organ damage. Investigators plan to investigate these novel
      markers in this trial. Investigators hypothesize that COVID-19 is a heightened
      prothrombotic/hypercoagulability state that can be characterized using platelet function
      testing and Thromboelastography. More information is required to study the effect of COVID-19
      on coagulation and platelet pathways to develop effective antithrombotic treatment
      strategies.

      The study is a multi-center, non-interventional study involving laboratory testing of blood
      samples and data collection for a COVID registry using electronic medical records. The study
      specific laboratory assessments will be obtained at baseline (closest to time of
      hospitalization), Day 3 and Day 8 from baseline, and at hospital discharge. Patients will be
      followed for clinical events during hospitalization, and 1 and 6 months after discharge.
      Patients (n=100) hospitalized at Sinai Hospital of Baltimore and Northwest Hospital with at
      least one of the following will be enrolled.

        1. With a confirmed diagnosis of COVID-19 infection using a positive RT-PCR or a positive
           IgG antibody test prior to or during hospitalization or,

        2. With a negative COVID-19 RT-PCR test but with symptoms of possible COVID-19infection
           and:

             1. an elevated D-dimer and/or

             2. positive imaging results showing unilateral or bilateral pneumonia or ground glass
                opacity in lungs.
observational model: Other
time perspective: Prospective
measure: Frequency of Hypercoagulability as measured by thromboelastography measured by TEG and platelet aggregation.
time frame: up to day 8
description: Frequency of Hypercoagulability as measured by point-of-care thromboelastography (TEG6s)
measure: Frequency of High Platelet Reactivity (HPR)
time frame: up to day 8
description: Incidence of High Platelet Reactivity as measured by platelet aggregation and TEG6s
measure: Frequency of thrombo-inflammatory syndrome
time frame: up to day 8
description: Frequency of thrombo -inflammatory syndrome as determined by D-Dimer and TEG6s
measure: Correlation between TEG6s parameters and clinical outcomes
time frame: through study completion, an average of 6 months
description: Correlation between TEG6s parameters and clinical outcomes (thrombotic and bleeding events, need for ventilation, death)
measure: Correlation between HPR and clinical outcomes
time frame: through study completion, an average of 6 months
description: Correlation between HPR and clinical outcomes (thrombotic and bleeding events, need for ventilation, death)
measure: Determine response to anticoagulation therapy
time frame: up to day 8
description: Determine response to anticoagulation therapy by calculating change in R-value (CK -CKH)
measure: Determine level of platelet aggregation
time frame: up to day 8
description: Determine level of platelet aggregation by impedance aggregometry
measure: Determine level of platelet aggregation
time frame: up to day 8
description: Determine percent platelet aggregation by TEG-6S platelet Mapping assay
measure: Determine platelet thrombi and fibrin rich platelet thrombus Area Under the Curve
time frame: up to day 8
description: Determine platelet thrombi and fibrin rich platelet thrombus Area Under the Curve using TTAS analyzer
measure: Determine short and long IgG, IgM and IgG antibody levels
time frame: up to day 6 months
description: Determine short and long IgG, IgM and IgG antibody levels against using multiple specimen types (saliva, whole blood, serum, plasma, urine)
intervention type: Diagnostic Test
intervention name: Phlebotomy
description: Serial assessment of hemostasis by blood and urine collection
Blood and urine samples will be collected at study timepoints for the following:

        1. TEG6S with citrated multi-channel and Platelet Mapping cartridges

        2. Platelet aggregation will be assessed using a Chronolog Lumi- Aggregometer

        3. Serum and Plasma Biomarkers of Inflammation/Cytokine Storm, Coagulation,and
           Ischemia/Organ Injury

        4. Urinary 11-dehydrothromboxane B2

        5. Evaluation of whole blood thrombogenicity using The Total Thrombus- Formation Analysis
           System (T-TAS)

        6. Genotyping: Genetic variations of single nucleotide polymorphisms (SNPs) related to
           coagulation, platelet function, immune response and thrombosis related clinical outcomes
           using SNP microarrays and PCR-based methods.

        7. COVID-19 Antibody Detection
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 3 Years
maximum age: N/A
healthy volunteers: No
last name: Paul A Gurbel, MD
role: Principal Investigator
affiliation: LifeBridge Health
last name: kevin bliden, MBA
phone: 4432441497
email: kbliden@lifebridgehealth.org
last name: Cescelle Barbour, MSN
phone: 4106014194
email: cbarbour@lifebridgehealth.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No