<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/NCT04441996</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00000949</org_study_id>
    <nct_id>NCT04441996</nct_id>
  </id_info>
  <brief_title>Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity</brief_title>
  <official_title>Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many patients with Coronavirus Disease 2019 (COVID-19) have atypical blood clots. These blood&#xD;
      clots can occur in either veins or arteries and be large, like in stroke or heart attack, or&#xD;
      very tiny, called microthrombi. Some patients with COVID-19 even have blood clots despite&#xD;
      being on anti-clotting medications. Blood with increased viscosity does not flow through the&#xD;
      body normally, in the same way that syrup, a highly viscous liquid, and water, a minimally&#xD;
      viscous liquid, flow differently. The researchers believe that hyperviscosity may contribute&#xD;
      to blood clots and organ damage seen in patients with severe COVID-19. Plasma exchange&#xD;
      removes a patient's plasma, which contains the large sticky factors that the researchers&#xD;
      believe are increasing viscosity, and replaces it with plasma from healthy donors. In&#xD;
      addition to providing important information about plasma exchange as a treatment in COVID-19&#xD;
      for patients, this study will provide data to justify resource and staffing decisions.&#xD;
&#xD;
      This study will enroll 20 participants who are critically ill from COVID-19. Participants&#xD;
      will be randomized to receive therapeutic plasma exchange (TPE) or standard of care (SOC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Critically ill COVID-19 patients have high rates of complications, including respiratory&#xD;
      failure, renal impairment, and a coagulopathic state that may exacerbate these conditions and&#xD;
      contribute to additional end organ injury. Consistent with a fundamentally distinct nature of&#xD;
      COVID-19-associated disease, our preliminary studies demonstrate that patients with COVID-19&#xD;
      exhibit an increase in plasma viscosity. Furthermore, the researchers have found that plasma&#xD;
      viscosity strongly correlates with sequential organ failure assessment (SOFA) scores, a&#xD;
      mortality prediction score used in the intensive care unit (ICU), in COVID-19 infected&#xD;
      patients. These results strongly suggest that altered blood flow secondary to hyperviscosity&#xD;
      may contribute to end organ injury and therefore morbidity and mortality in the most&#xD;
      critically ill COVID-19 patients. More detailed analysis of the potential etiology of&#xD;
      COVID-19-associated plasma hyperviscosity has demonstrated that these patients also have&#xD;
      significantly elevated levels of the plasma protein fibrinogen. Increased fibrinogen levels,&#xD;
      which may be either entirely responsible for or at least contribute to hyperviscosity in&#xD;
      these patients, may be the primary mediator of refractory hypercoagulability in this patient&#xD;
      population. Thus, hyperviscosity induced by hyperfibrinogenemia may be a critical driver of&#xD;
      morbidity and mortality in patients with COVID-19.&#xD;
&#xD;
      Therapeutic plasma exchange (TPE) is the only procedure known to directly and rapidly&#xD;
      decrease plasma viscosity, suggesting that TPE may improve patient outcomes in critically ill&#xD;
      patients with COVID-19 by decreasing plasma viscosity and thereby enhancing blood flow.&#xD;
      However, as a procedure, extensive implementation of TPE would require significant devotion&#xD;
      of hospital resources, including apheresis machines and the staff needed to successfully&#xD;
      conduct these procedures. The procedures alone require staff to have prolonged interactions&#xD;
      with critically ill COVID-19 patients, placing them at a potentially increased risk for&#xD;
      contracting COVID-19. It is therefore essential that clear and unequivocal data be generated&#xD;
      in order to accurately assess the risk and benefits of this procedure for both patients and&#xD;
      staff. Such data will also aid in determining the necessary resources that may be needed to&#xD;
      successfully conduct TPE for this patient population.&#xD;
&#xD;
      Participants will be randomized in a 1:1 ratio to receive TPE or SOC. Participants in the TPE&#xD;
      study arm will receive two treatments of TPE with frozen plasma on sequential days. Plasma&#xD;
      viscosity will be measured before TPE (Day 1) and following the second TPE treatment (Day 3&#xD;
      or 4). Participants in the SOC study arm will also have their plasma viscosity assessed on&#xD;
      Days 1 and 3. Participants will be followed for the duration of their hospital stay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2020</start_date>
  <completion_date type="Actual">March 18, 2021</completion_date>
  <primary_completion_date type="Actual">March 18, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma Viscosity</measure>
    <time_frame>Day 1 (within 24 hours prior to TPE), Day 4 (within 24 hours of last TPE)</time_frame>
    <description>Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Incidence of Adverse Events</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative All Cause Mortality</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>The number of participants dying from any cause is reported as a cumulative measures of mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Count of Bleeding and Thromboembolic Complications</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots. The values reported are cumulative.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Treatment Failure</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>Time to treatment failure will be assessed in days and is defined as plasma viscosity &gt; 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU Stay</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospital Stay</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Discharge Disposition</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Status Score</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with &quot;terminal&quot; scores carried over from the measure before for those that expired or fully recovered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Temperature</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Body temperature will be assessed in degrees Celsius.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systolic Blood Pressure</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diastolic Blood Pressure</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Heart rate will be assessed as beats per minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Rate</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Respiratory rate will be assessed as breaths per minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator Days</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator Oxygen Percent (FiO2)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive End-Expiratory Pressure (PEEP)</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vasopressor Requirements</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Whether or not breathing assistance from vasopressors is needed will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for Treatment From a Registered Respiratory Therapist (RRT)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Whether or not breathing assistance from an RRT is needed will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sequential Organ Failure Assessment (SOFA) Score</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Ratio</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>White Blood Count (WBC)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin (Hb)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematocrit (Hct)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Count</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Platelet Volume (MVP)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Urea Nitrogen (BUN)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creatinine</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bilirubin</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Protein</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Albumin</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive Protein (CRP)</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin 6 (IL-6)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prothrombin Time (PT)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International Normalized Ratio (INR)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activated Partial Thromboplastin Time (aPTT)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-factor Xa (Anti-Xa)</measure>
    <time_frame>Days 7, 14, 21, and 28</time_frame>
    <description>The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrinogen</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-dimer</measure>
    <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
    <description>The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Therapeutic plasma exchange (TPE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with COVID-19-associated hyperviscosity randomized to receive therapeutic plasma exchange (TPE).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants with COVID-19-associated hyperviscosity randomized to receive standard of care treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Therapeutic plasma exchange (TPE)</intervention_name>
    <description>Participants will receive two treatments of TPE with frozen plasma (FP) replacement on two sequential days (Day 2 and Day 3). All procedures will be performed by the apheresis staff at the hospital sites, following institutional standard operating procedures. FP will be obtained from American Red Cross or LifeSouth Community Blood centers.</description>
    <arm_group_label>Therapeutic plasma exchange (TPE)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of care</intervention_name>
    <description>Participants will continue to receive standard of care and be closely monitored by ICU team for any change in clinical status, and any adverse events directly related to study intervention will be reported to the study investigator.</description>
    <arm_group_label>Standard of care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Patients admitted to the ICU at Emory University Hospital, Emory University Hospital&#xD;
             Midtown, or Emory Saint Joseph's Hospital&#xD;
&#xD;
          -  Evidence of COVID-19 infection documented by a laboratory test either by one of the&#xD;
             following:&#xD;
&#xD;
               -  A diagnostic test (e.g., nasopharyngeal swab, tracheal aspirate, other)&#xD;
&#xD;
               -  Positive serological test for severe acute respiratory syndrome coronavirus 2&#xD;
                  (SARS-CoV-2) antibodies&#xD;
&#xD;
               -  Medical records from outside institution&#xD;
&#xD;
          -  Plasma viscosity &gt;2.3 and &lt;3.5 centipoise (cp) or Fibrinogen &gt;800 mg/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with plasma viscosity &gt; 3.5 cp&#xD;
&#xD;
          -  Moribund patients that the ICU clinical team expects to die within 24 hours&#xD;
&#xD;
          -  Patients with any condition that, in the opinion of the clinical team or investigator,&#xD;
             could increase the subject's risk by participating in the study or confound the&#xD;
             outcome of the study&#xD;
&#xD;
          -  Patients participating in another clinical trial that prohibits the use of TPE&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Prisoners&#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>Cheryl Maier, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory Saint Joseph's Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <results_first_submitted>October 28, 2022</results_first_submitted>
  <results_first_submitted_qc>November 29, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 21, 2022</results_first_posted>
  <disposition_first_submitted>December 8, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>November 29, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">December 21, 2022</disposition_first_posted>
  <last_update_submitted>November 29, 2022</last_update_submitted>
  <last_update_submitted_qc>November 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Cheryl Maier</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Hyperviscosity</keyword>
  <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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT04441996/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from Emory University Hospital, Emory University Hospital Midtown, and Emory Saint Joseph's Hospital in Atlanta, Georgia, USA. Participant enrollment began July 17, 2020 and all follow-up assessments were completed by March 18, 2021.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Therapeutic Plasma Exchange (TPE)</title>
          <description>Participants with Coronavirus Disease 2019 (COVID-19) associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care</title>
          <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Therapeutic Plasma Exchange (TPE)</title>
          <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care</title>
          <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.9" spread="14.4"/>
                    <measurement group_id="B2" value="58.8" spread="9.04"/>
                    <measurement group_id="B3" value="58.9" spread="11.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Plasma Viscosity</title>
        <description>Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.</description>
        <time_frame>Day 1 (within 24 hours prior to TPE), Day 4 (within 24 hours of last TPE)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Viscosity</title>
          <description>Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.</description>
          <units>cP</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.35" spread="0.37"/>
                    <measurement group_id="O2" value="2.47" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.61" spread="0.09"/>
                    <measurement group_id="O2" value="2.47" spread="0.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cumulative Incidence of Adverse Events</title>
        <description>The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.</description>
        <time_frame>Up to Day 28</time_frame>
        <population>This analysis includes participants in the TPE study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Incidence of Adverse Events</title>
          <description>The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.</description>
          <population>This analysis includes participants in the TPE study arm.</population>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative All Cause Mortality</title>
        <description>The number of participants dying from any cause is reported as a cumulative measures of mortality.</description>
        <time_frame>Up to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative All Cause Mortality</title>
          <description>The number of participants dying from any cause is reported as a cumulative measures of mortality.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 to Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Count of Bleeding and Thromboembolic Complications</title>
        <description>The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots. The values reported are cumulative.</description>
        <time_frame>Up to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Count of Bleeding and Thromboembolic Complications</title>
          <description>The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots. The values reported are cumulative.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 to Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 to Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Treatment Failure</title>
        <description>Time to treatment failure will be assessed in days and is defined as plasma viscosity &gt; 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.</description>
        <time_frame>Up to Day 28</time_frame>
        <population>This analysis includes participants experiencing treatment failure.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Treatment Failure</title>
          <description>Time to treatment failure will be assessed in days and is defined as plasma viscosity &gt; 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.</description>
          <population>This analysis includes participants experiencing treatment failure.</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="2.12"/>
                    <measurement group_id="O2" value="2.5" spread="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of ICU Stay</title>
        <description>The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.</description>
        <time_frame>Up to Day 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of ICU Stay</title>
          <description>The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1" spread="15.7"/>
                    <measurement group_id="O2" value="16.0" spread="11.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospital Stay</title>
        <description>The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.</description>
        <time_frame>Up to Day 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospital Stay</title>
          <description>The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.2" spread="12.4"/>
                    <measurement group_id="O2" value="21.7" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Discharge Disposition</title>
        <description>The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.</description>
        <time_frame>Up to Day 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Discharge Disposition</title>
          <description>The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Home or LTAC</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Palliative care or death</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Status Score</title>
        <description>The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with &quot;terminal&quot; scores carried over from the measure before for those that expired or fully recovered.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Status Score</title>
          <description>The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with &quot;terminal&quot; scores carried over from the measure before for those that expired or fully recovered.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" lower_limit="6.0" upper_limit="7.75"/>
                    <measurement group_id="O2" value="8.0" lower_limit="7.25" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (1 day after second TPE treatment)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" lower_limit="6.0" upper_limit="7.0"/>
                    <measurement group_id="O2" value="8.0" lower_limit="7.25" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" lower_limit="6.0" upper_limit="8.0"/>
                    <measurement group_id="O2" value="8.0" lower_limit="7.0" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="6.0" upper_limit="8.0"/>
                    <measurement group_id="O2" value="7.5" lower_limit="7.0" upper_limit="9.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" lower_limit="5.5" upper_limit="8.0"/>
                    <measurement group_id="O2" value="8.0" lower_limit="7.0" upper_limit="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" lower_limit="5.5" upper_limit="8.75"/>
                    <measurement group_id="O2" value="10.0" lower_limit="7.0" upper_limit="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Body Temperature</title>
        <description>Body temperature will be assessed in degrees Celsius.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Body temperature was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Body Temperature</title>
          <description>Body temperature will be assessed in degrees Celsius.</description>
          <population>Body temperature was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systolic Blood Pressure</title>
        <description>Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Systolic Blood Pressure</title>
          <description>Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).</description>
          <population>Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Diastolic Blood Pressure</title>
        <description>Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Diastolic Blood Pressure</title>
          <description>Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).</description>
          <population>Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Heart Rate</title>
        <description>Heart rate will be assessed as beats per minute.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Heart rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate</title>
          <description>Heart rate will be assessed as beats per minute.</description>
          <population>Heart rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Rate</title>
        <description>Respiratory rate will be assessed as breaths per minute.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Respiratory rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Rate</title>
          <description>Respiratory rate will be assessed as breaths per minute.</description>
          <population>Respiratory rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilator Days</title>
        <description>The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.</description>
        <time_frame>Up to Day 28</time_frame>
        <population>This analysis includes participants who were on a ventilator; two participants in the TPE arm were never on a ventilator.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilator Days</title>
          <description>The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.</description>
          <population>This analysis includes participants who were on a ventilator; two participants in the TPE arm were never on a ventilator.</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.6" spread="11.6"/>
                    <measurement group_id="O2" value="19.2" spread="11.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilator Oxygen Percent (FiO2)</title>
        <description>The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>FiO2 was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilator Oxygen Percent (FiO2)</title>
          <description>The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.</description>
          <population>FiO2 was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Positive End-Expiratory Pressure (PEEP)</title>
        <description>PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants who were assessed for PEEP at the indicated time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Positive End-Expiratory Pressure (PEEP)</title>
          <description>PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.</description>
          <population>This analysis includes participants who were assessed for PEEP at the indicated time point.</population>
          <units>cmH2O</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" spread="5.0"/>
                    <measurement group_id="O2" value="15.9" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="4.3"/>
                    <measurement group_id="O2" value="13.0" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" spread="6.2"/>
                    <measurement group_id="O2" value="11.3" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" spread="2.0"/>
                    <measurement group_id="O2" value="13.3" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" spread="1.2"/>
                    <measurement group_id="O2" value="11.0" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" spread="2.6"/>
                    <measurement group_id="O2" value="12.7" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vasopressor Requirements</title>
        <description>Whether or not breathing assistance from vasopressors is needed will be compared between study arms.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Vasopressor requirements were not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Vasopressor Requirements</title>
          <description>Whether or not breathing assistance from vasopressors is needed will be compared between study arms.</description>
          <population>Vasopressor requirements were not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Need for Treatment From a Registered Respiratory Therapist (RRT)</title>
        <description>Whether or not breathing assistance from an RRT is needed will be compared between study arms.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Need for treatment from an RRT was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Need for Treatment From a Registered Respiratory Therapist (RRT)</title>
          <description>Whether or not breathing assistance from an RRT is needed will be compared between study arms.</description>
          <population>Need for treatment from an RRT was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sequential Organ Failure Assessment (SOFA) Score</title>
        <description>The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants who had a SOFA score assessment at the indicated time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Sequential Organ Failure Assessment (SOFA) Score</title>
          <description>The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.</description>
          <population>This analysis includes participants who had a SOFA score assessment at the indicated time point.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" lower_limit="8.5" upper_limit="12.75"/>
                    <measurement group_id="O2" value="13.0" lower_limit="11.25" upper_limit="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" lower_limit="7.75" upper_limit="12.5"/>
                    <measurement group_id="O2" value="11.5" lower_limit="11.0" upper_limit="12.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" lower_limit="10.0" upper_limit="12.0"/>
                    <measurement group_id="O2" value="12.0" lower_limit="11.25" upper_limit="13.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" lower_limit="8.75" upper_limit="13.75"/>
                    <measurement group_id="O2" value="12.5" lower_limit="11.0" upper_limit="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5" lower_limit="8.75" upper_limit="12.0"/>
                    <measurement group_id="O2" value="13.0" lower_limit="10.75" upper_limit="15.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5" lower_limit="8.25" upper_limit="12.75"/>
                    <measurement group_id="O2" value="12.0" lower_limit="9.0" upper_limit="15.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio</title>
        <description>The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants with available arterial blood gas (ABG) values.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio</title>
          <description>The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).</description>
          <population>This analysis includes participants with available arterial blood gas (ABG) values.</population>
          <units>PaO2/FiO2 ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="219" spread="102"/>
                    <measurement group_id="O2" value="166" spread="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="132" spread="80"/>
                    <measurement group_id="O2" value="157" spread="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="151" spread="131"/>
                    <measurement group_id="O2" value="141" spread="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109" spread="21"/>
                    <measurement group_id="O2" value="101" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104" spread="32"/>
                    <measurement group_id="O2" value="145" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108" spread="54"/>
                    <measurement group_id="O2" value="146" spread="127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Ratio</title>
        <description>Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for calculating the ventilatory ratio was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Ratio</title>
          <description>Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).</description>
          <population>Information for calculating the ventilatory ratio was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>White Blood Count (WBC)</title>
        <description>The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>White Blood Count (WBC)</title>
          <description>The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hemoglobin (Hb)</title>
        <description>Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Hemoglobin (Hb)</title>
          <description>Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hematocrit (Hct)</title>
        <description>A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematocrit (Hct)</title>
          <description>A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Count</title>
        <description>A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Count</title>
          <description>A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Platelet Volume (MVP)</title>
        <description>MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Platelet Volume (MVP)</title>
          <description>MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Blood Urea Nitrogen (BUN)</title>
        <description>The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Blood Urea Nitrogen (BUN)</title>
          <description>The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Creatinine</title>
        <description>The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants who had creatinine assessed at the indicated time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Creatinine</title>
          <description>The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.</description>
          <population>This analysis includes participants who had creatinine assessed at the indicated time point.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="2.1"/>
                    <measurement group_id="O2" value="2.9" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="1.3"/>
                    <measurement group_id="O2" value="2.6" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="1.4"/>
                    <measurement group_id="O2" value="2.6" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="2.3"/>
                    <measurement group_id="O2" value="2.7" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="3.3"/>
                    <measurement group_id="O2" value="2.8" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="1.6"/>
                    <measurement group_id="O2" value="2.0" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bilirubin</title>
        <description>For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Bilirubin</title>
          <description>For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Protein</title>
        <description>The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Protein</title>
          <description>The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Albumin</title>
        <description>The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Albumin</title>
          <description>The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>C-reactive Protein (CRP)</title>
        <description>A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants who had CRP assessed at the indicated time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>C-reactive Protein (CRP)</title>
          <description>A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.</description>
          <population>This analysis includes participants who had CRP assessed at the indicated time point.</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="226" spread="74"/>
                    <measurement group_id="O2" value="234" spread="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83" spread="37"/>
                    <measurement group_id="O2" value="179" spread="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153" spread="153"/>
                    <measurement group_id="O2" value="210" spread="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119" spread="94"/>
                    <measurement group_id="O2" value="195" spread="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="149" spread="134"/>
                    <measurement group_id="O2" value="71" spread="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="215" spread="213"/>
                    <measurement group_id="O2" value="141" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin 6 (IL-6)</title>
        <description>A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin 6 (IL-6)</title>
          <description>A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Prothrombin Time (PT)</title>
        <description>Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Prothrombin Time (PT)</title>
          <description>Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>International Normalized Ratio (INR)</title>
        <description>An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>International Normalized Ratio (INR)</title>
          <description>An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Activated Partial Thromboplastin Time (aPTT)</title>
        <description>The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Activated Partial Thromboplastin Time (aPTT)</title>
          <description>The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anti-factor Xa (Anti-Xa)</title>
        <description>The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).</description>
        <time_frame>Days 7, 14, 21, and 28</time_frame>
        <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Anti-factor Xa (Anti-Xa)</title>
          <description>The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).</description>
          <population>Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fibrinogen</title>
        <description>Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants who had fibrinogen assessed at the indicated time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Fibrinogen</title>
          <description>Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.</description>
          <population>This analysis includes participants who had fibrinogen assessed at the indicated time point.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="934" spread="79"/>
                    <measurement group_id="O2" value="860" spread="182"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="359" spread="71"/>
                    <measurement group_id="O2" value="807" spread="199"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="663" spread="166"/>
                    <measurement group_id="O2" value="806" spread="189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="593" spread="143"/>
                    <measurement group_id="O2" value="762" spread="145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="687" spread="125"/>
                    <measurement group_id="O2" value="598" spread="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="693" spread="33"/>
                    <measurement group_id="O2" value="116" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>D-dimer</title>
        <description>The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.</description>
        <time_frame>Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28</time_frame>
        <population>This analysis includes participants who had D-dimer at the indicated time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Therapeutic Plasma Exchange (TPE)</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>D-dimer</title>
          <description>The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.</description>
          <population>This analysis includes participants who had D-dimer at the indicated time point.</population>
          <units>mcg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (day of study enrollment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5187" spread="8973"/>
                    <measurement group_id="O2" value="1632" spread="1163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 (one day after second TPE treatment)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3519" spread="5575"/>
                    <measurement group_id="O2" value="6253" spread="9325"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4041" spread="6408"/>
                    <measurement group_id="O2" value="1749" spread="1126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1819" spread="650"/>
                    <measurement group_id="O2" value="6767" spread="8304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6765" spread="13044"/>
                    <measurement group_id="O2" value="3136" spread="1911"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16648" spread="28942"/>
                    <measurement group_id="O2" value="6567" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Information on TPE-associated adverse events was collected in patients receiving the study intervention (TPE) beginning with the initiation of the first TPE and continued up to 28 days after study enrollment. Adverse events were not collected for participants in the standard of care study arm.</time_frame>
      <desc>Adverse events were limited to TPE-associated complications of: hypotension, hypocalcemia, citrate toxicity, angiotensin-converting enzyme (ACE) inhibitor reactions, transfusion-associated circulatory overload, transfusion-related acute lung injury, transfusion-associated dyspnea, allergic reaction, hypotensive transfusion reaction, febrile non-hemolytic transfusion reaction, acute hemolytic transfusion reaction, delayed hemolytic transfusion reaction, and transfusion-transmitted infection.</desc>
      <group_list>
        <group group_id="E1">
          <title>Therapeutic Plasma Exchange (TPE)</title>
          <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care</title>
          <description>Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Mild tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Cheryl Maier MD, PhD</name_or_title>
      <organization>Emory University</organization>
      <phone>404-712-2795</phone>
      <email>cheryl.maier@emory.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04441996
org study id: STUDY00000949
nct id: NCT04441996
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Many patients with Coronavirus Disease 2019 (COVID-19) have atypical blood clots. These blood
      clots can occur in either veins or arteries and be large, like in stroke or heart attack, or
      very tiny, called microthrombi. Some patients with COVID-19 even have blood clots despite
      being on anti-clotting medications. Blood with increased viscosity does not flow through the
      body normally, in the same way that syrup, a highly viscous liquid, and water, a minimally
      viscous liquid, flow differently. The researchers believe that hyperviscosity may contribute
      to blood clots and organ damage seen in patients with severe COVID-19. Plasma exchange
      removes a patient's plasma, which contains the large sticky factors that the researchers
      believe are increasing viscosity, and replaces it with plasma from healthy donors. In
      addition to providing important information about plasma exchange as a treatment in COVID-19
      for patients, this study will provide data to justify resource and staffing decisions.

      This study will enroll 20 participants who are critically ill from COVID-19. Participants
      will be randomized to receive therapeutic plasma exchange (TPE) or standard of care (SOC).
Critically ill COVID-19 patients have high rates of complications, including respiratory
      failure, renal impairment, and a coagulopathic state that may exacerbate these conditions and
      contribute to additional end organ injury. Consistent with a fundamentally distinct nature of
      COVID-19-associated disease, our preliminary studies demonstrate that patients with COVID-19
      exhibit an increase in plasma viscosity. Furthermore, the researchers have found that plasma
      viscosity strongly correlates with sequential organ failure assessment (SOFA) scores, a
      mortality prediction score used in the intensive care unit (ICU), in COVID-19 infected
      patients. These results strongly suggest that altered blood flow secondary to hyperviscosity
      may contribute to end organ injury and therefore morbidity and mortality in the most
      critically ill COVID-19 patients. More detailed analysis of the potential etiology of
      COVID-19-associated plasma hyperviscosity has demonstrated that these patients also have
      significantly elevated levels of the plasma protein fibrinogen. Increased fibrinogen levels,
      which may be either entirely responsible for or at least contribute to hyperviscosity in
      these patients, may be the primary mediator of refractory hypercoagulability in this patient
      population. Thus, hyperviscosity induced by hyperfibrinogenemia may be a critical driver of
      morbidity and mortality in patients with COVID-19.

      Therapeutic plasma exchange (TPE) is the only procedure known to directly and rapidly
      decrease plasma viscosity, suggesting that TPE may improve patient outcomes in critically ill
      patients with COVID-19 by decreasing plasma viscosity and thereby enhancing blood flow.
      However, as a procedure, extensive implementation of TPE would require significant devotion
      of hospital resources, including apheresis machines and the staff needed to successfully
      conduct these procedures. The procedures alone require staff to have prolonged interactions
      with critically ill COVID-19 patients, placing them at a potentially increased risk for
      contracting COVID-19. It is therefore essential that clear and unequivocal data be generated
      in order to accurately assess the risk and benefits of this procedure for both patients and
      staff. Such data will also aid in determining the necessary resources that may be needed to
      successfully conduct TPE for this patient population.

      Participants will be randomized in a 1:1 ratio to receive TPE or SOC. Participants in the TPE
      study arm will receive two treatments of TPE with frozen plasma on sequential days. Plasma
      viscosity will be measured before TPE (Day 1) and following the second TPE treatment (Day 3
      or 4). Participants in the SOC study arm will also have their plasma viscosity assessed on
      Days 1 and 3. Participants will be followed for the duration of their hospital stay.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Plasma Viscosity
time frame: Day 1 (within 24 hours prior to TPE), Day 4 (within 24 hours of last TPE)
description: Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.
measure: Cumulative Incidence of Adverse Events
time frame: Up to Day 28
description: The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.
measure: Cumulative All Cause Mortality
time frame: Up to Day 28
description: The number of participants dying from any cause is reported as a cumulative measures of mortality.
measure: Cumulative Count of Bleeding and Thromboembolic Complications
time frame: Up to Day 28
description: The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots. The values reported are cumulative.
measure: Time to Treatment Failure
time frame: Up to Day 28
description: Time to treatment failure will be assessed in days and is defined as plasma viscosity > 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.
measure: Duration of ICU Stay
time frame: Up to Day 48
description: The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.
measure: Duration of Hospital Stay
time frame: Up to Day 48
description: The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.
measure: Discharge Disposition
time frame: Up to Day 48
description: The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.
measure: Clinical Status Score
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with "terminal" scores carried over from the measure before for those that expired or fully recovered.
measure: Body Temperature
time frame: Days 7, 14, 21, and 28
description: Body temperature will be assessed in degrees Celsius.
measure: Systolic Blood Pressure
time frame: Days 7, 14, 21, and 28
description: Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).
measure: Diastolic Blood Pressure
time frame: Days 7, 14, 21, and 28
description: Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).
measure: Heart Rate
time frame: Days 7, 14, 21, and 28
description: Heart rate will be assessed as beats per minute.
measure: Respiratory Rate
time frame: Days 7, 14, 21, and 28
description: Respiratory rate will be assessed as breaths per minute.
measure: Ventilator Days
time frame: Up to Day 28
description: The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.
measure: Ventilator Oxygen Percent (FiO2)
time frame: Days 7, 14, 21, and 28
description: The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.
measure: Positive End-Expiratory Pressure (PEEP)
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.
measure: Vasopressor Requirements
time frame: Days 7, 14, 21, and 28
description: Whether or not breathing assistance from vasopressors is needed will be compared between study arms.
measure: Need for Treatment From a Registered Respiratory Therapist (RRT)
time frame: Days 7, 14, 21, and 28
description: Whether or not breathing assistance from an RRT is needed will be compared between study arms.
measure: Sequential Organ Failure Assessment (SOFA) Score
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.
measure: Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).
measure: Ventilatory Ratio
time frame: Days 7, 14, 21, and 28
description: Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).
measure: White Blood Count (WBC)
time frame: Days 7, 14, 21, and 28
description: The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.
measure: Hemoglobin (Hb)
time frame: Days 7, 14, 21, and 28
description: Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.
measure: Hematocrit (Hct)
time frame: Days 7, 14, 21, and 28
description: A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%
measure: Platelet Count
time frame: Days 7, 14, 21, and 28
description: A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.
measure: Mean Platelet Volume (MVP)
time frame: Days 7, 14, 21, and 28
description: MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).
measure: Blood Urea Nitrogen (BUN)
time frame: Days 7, 14, 21, and 28
description: The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.
measure: Creatinine
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.
measure: Bilirubin
time frame: Days 7, 14, 21, and 28
description: For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.
measure: Total Protein
time frame: Days 7, 14, 21, and 28
description: The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.
measure: Albumin
time frame: Days 7, 14, 21, and 28
description: The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.
measure: C-reactive Protein (CRP)
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.
measure: Interleukin 6 (IL-6)
time frame: Days 7, 14, 21, and 28
description: A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.
measure: Prothrombin Time (PT)
time frame: Days 7, 14, 21, and 28
description: Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.
measure: International Normalized Ratio (INR)
time frame: Days 7, 14, 21, and 28
description: An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.
measure: Activated Partial Thromboplastin Time (aPTT)
time frame: Days 7, 14, 21, and 28
description: The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.
measure: Anti-factor Xa (Anti-Xa)
time frame: Days 7, 14, 21, and 28
description: The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).
measure: Fibrinogen
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.
measure: D-dimer
time frame: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28
description: The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.
arm group label: Therapeutic plasma exchange (TPE)
arm group type: Experimental
description: Participants with COVID-19-associated hyperviscosity randomized to receive therapeutic plasma exchange (TPE).
arm group label: Standard of care
arm group type: Active Comparator
description: Participants with COVID-19-associated hyperviscosity randomized to receive standard of care treatment.
intervention type: Biological
intervention name: Therapeutic plasma exchange (TPE)
description: Participants will receive two treatments of TPE with frozen plasma (FP) replacement on two sequential days (Day 2 and Day 3). All procedures will be performed by the apheresis staff at the hospital sites, following institutional standard operating procedures. FP will be obtained from American Red Cross or LifeSouth Community Blood centers.
arm group label: Therapeutic plasma exchange (TPE)
intervention type: Other
intervention name: Standard of care
description: Participants will continue to receive standard of care and be closely monitored by ICU team for any change in clinical status, and any adverse events directly related to study intervention will be reported to the study investigator.
arm group label: Standard of care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cheryl Maier, MD, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Cheryl Maier
investigator title: Assistant Professor
mesh term: COVID-19
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 