<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/NCT04497389</url>
  </required_header>
  <id_info>
    <org_study_id>132922</org_study_id>
    <nct_id>NCT04497389</nct_id>
  </id_info>
  <brief_title>Safety and Feasibility of Amniotic Fluid as a Treatment for COVID-19 Patients</brief_title>
  <official_title>A Phase I/II Randomized Double-blinded Placebo-controlled Clinical Trial to Determine Safety and Feasibility of Using an Acellular Sterile Filtered Amniotic Fluid as a Treatment for COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to explore the effectiveness of processed human amniotic fluid&#xD;
      as a treatment for COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Past use of human amniotic products (i.e., membrane and fluid) has previously been&#xD;
      FDA-approved as a human cells, Tissues, and Cellular and Tissue-Based Products (HCT/P) under&#xD;
      21 CFR 1271 for tissue injury; and has been used to reduce inflammation and fibrosis in&#xD;
      patients with a variety of ailments. Given this, the investigators hypothesize that&#xD;
      intravenously (IV) administered processed sterile filtered amniotic fluid will reduce&#xD;
      inflammation in COVID-19 patients, and improve secondary clinical outcomes. Specifically, the&#xD;
      investigators hypothesize that patients who receive IV administered hAF will see a 50%&#xD;
      reduction in mean C-reactive protein levels following treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 28, 2020</start_date>
  <completion_date type="Anticipated">September 15, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 15, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>C-reactive protein</measure>
    <time_frame>Baseline through post-treatment (6 days)</time_frame>
    <description>Assess reduction of inflammation in COVID-19 patients, potentially leading to a decrease in the need for critical care. This will be assessed by measurement of C-reactive protein levels before and after the intervention. Units: mg/dL</description>
  </primary_outcome>
  <other_outcome>
    <measure>Death within 30 Days</measure>
    <time_frame>Baseline through 30 days</time_frame>
    <description>Comparison of mortality between intervention and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>ICU-free days at 30 days</measure>
    <time_frame>Baseline through 30 days</time_frame>
    <description>Comparison of days spend in ICU between intervention and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>From date of hospital admission through date of discharge or death, whichever comes first (up to 100 days)</time_frame>
    <description>Comparison of days spent in hospital between intervention and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Need for invasive mechanical ventilation</measure>
    <time_frame>From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)</time_frame>
    <description>Comparison of mechanical ventilation incidence between intervention and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker levels (interleukin-6)</measure>
    <time_frame>Baseline through post-treatment (6 days)</time_frame>
    <description>Comparison of mean biomarker level change between intervention and control groups. Units: pg/mL</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker levels (d-dimer)</measure>
    <time_frame>Baseline through post-treatment (6 days)</time_frame>
    <description>Comparison of mean biomarker level change between intervention and control groups. Units: ug/mL</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker levels (lactate dehydrogenase)</measure>
    <time_frame>Baseline through post-treatment (6 days)</time_frame>
    <description>Comparison of mean biomarker level change between intervention and control groups. Units: u/L</description>
  </other_outcome>
  <other_outcome>
    <measure>Need for ECMO</measure>
    <time_frame>From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)</time_frame>
    <description>Comparison of ECMO incidence between intervention and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Major adverse cardiac events</measure>
    <time_frame>From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)</time_frame>
    <description>Compare frequency of major adverse cardiac events (MACE) between intervention and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Patient-reported functional status</measure>
    <time_frame>Administered at 1, 3, 6, and 12 months post discharge (1 year)</time_frame>
    <description>Comparison of PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire results on a computer-adaptive platform between intervention and control groups using T-scores. Scale mean = 50, standard deviation = 10.</description>
  </other_outcome>
  <other_outcome>
    <measure>PTSD Checklist</measure>
    <time_frame>Administered at 1, 3, 6, and 12 months post discharge (1 year)</time_frame>
    <description>Patients will be administered a 20-question self-report measure of PTSD symptoms. Total scores range from 0-80. Scores of 31-33 or above generally indicate clinically likely PTSD.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>SARS CoV-2</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10ml intravenous hAF QD for 5 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>10 mL normal saline QD for 5 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human Amniotic Fluid</intervention_name>
    <description>Patients will receive 10ml intravenous hAF each day for 5 consecutive days.</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Age &gt;18&#xD;
&#xD;
          2. SARS CoV-2 laboratory positive test, obtained within 14 days of enrollment&#xD;
&#xD;
          3. Hospitalized&#xD;
&#xD;
          4. COVID-19 symptomatic (cough, fevers, shortness of breath, and/or sputum production)&#xD;
&#xD;
          5. Has a room air pulse oximetry of ≤94% and requires supplemental oxygen therapy&#xD;
&#xD;
          6. Patients of childbearing potential who agree to use acceptable methods of&#xD;
             contraception for 90 days after last administration of study IP&#xD;
&#xD;
          7. Patients who are receiving standard of care therapies for COVID-19 that are not FDA&#xD;
             approved are eligible for this study&#xD;
&#xD;
          8. Subjects must be able to consent to the study (i.e., Glasgow Coma Scale score of ≥14)&#xD;
&#xD;
          9. Patients are required to have controlled blood pressure of &lt;160/96 and a pulse of&#xD;
             &lt;110.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Patients on invasive mechanical ventilation (e.g., endotracheal intubation)&#xD;
&#xD;
          2. Chronic home oxygen utilization&#xD;
&#xD;
          3. Home or current use of immunosuppressive medications (including steroids)&#xD;
&#xD;
          4. Women who are pregnant, breastfeeding, or become pregnant during the study&#xD;
&#xD;
          5. Patients on non-invasive positive pressure ventilation&#xD;
&#xD;
          6. Patients on &gt;12 liters per minute via non-rebreather (NRB) or &gt;80% oxygen via high&#xD;
             flow nasal cannula&#xD;
&#xD;
          7. Patients who, in the opinion of the PI, have impending respiratory failure, defined as&#xD;
             requiring rapidly escalating oxygen supplementation&#xD;
&#xD;
          8. Patients with a hemoglobin &lt;9 mg/dL&#xD;
&#xD;
          9. Patients diagnosed with Stage 4 or 5 chronic kidney disease (CKD)&#xD;
&#xD;
         10. Patients with diagnosed NYHA class 4 or 5 congestive heart failure&#xD;
&#xD;
         11. Patients with a left ventricular assist device (LVAD)&#xD;
&#xD;
         12. Patients with thromboembolic phenomena&#xD;
&#xD;
         13. Patients with Type 2 and above heart block&#xD;
&#xD;
         14. Patients with established positive bacterial blood cultures prior to enrollment&#xD;
&#xD;
         15. Patients with ongoing pericardial effusion or ascites&#xD;
&#xD;
         16. Patients with clinically significant arrhythmia&#xD;
&#xD;
         17. Patients with liver function tests (ALT or AST) &gt;3x normal&#xD;
&#xD;
         18. Patients with untreated HIV infection&#xD;
&#xD;
         19. Patients diagnosed with end-stage organ disease&#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>Craig Selzman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Craig Selzman, MD</last_name>
    <phone>8015815311</phone>
    <email>craig.selzman@hsc.utah.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alyssa Messina, MA</last_name>
    <phone>8015853752</phone>
    <email>alyssa.messina@hsc.utah.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Utah Health</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Craig Selzman, MD</last_name>
      <phone>801-581-5311</phone>
      <email>craig.selzman@hsc.utah.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>November 4, 2020</last_update_submitted>
  <last_update_submitted_qc>November 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Craig Selzman</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>Amniotic fluid</keyword>
  <keyword>COVID-19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04497389
org study id: 132922
nct id: NCT04497389
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to explore the effectiveness of processed human amniotic fluid
      as a treatment for COVID-19.
Past use of human amniotic products (i.e., membrane and fluid) has previously been
      FDA-approved as a human cells, Tissues, and Cellular and Tissue-Based Products (HCT/P) under
      21 CFR 1271 for tissue injury; and has been used to reduce inflammation and fibrosis in
      patients with a variety of ailments. Given this, the investigators hypothesize that
      intravenously (IV) administered processed sterile filtered amniotic fluid will reduce
      inflammation in COVID-19 patients, and improve secondary clinical outcomes. Specifically, the
      investigators hypothesize that patients who receive IV administered hAF will see a 50%
      reduction in mean C-reactive protein levels following treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: C-reactive protein
time frame: Baseline through post-treatment (6 days)
description: Assess reduction of inflammation in COVID-19 patients, potentially leading to a decrease in the need for critical care. This will be assessed by measurement of C-reactive protein levels before and after the intervention. Units: mg/dL
measure: Death within 30 Days
time frame: Baseline through 30 days
description: Comparison of mortality between intervention and control groups
measure: ICU-free days at 30 days
time frame: Baseline through 30 days
description: Comparison of days spend in ICU between intervention and control groups
measure: Hospital length of stay
time frame: From date of hospital admission through date of discharge or death, whichever comes first (up to 100 days)
description: Comparison of days spent in hospital between intervention and control groups
measure: Need for invasive mechanical ventilation
time frame: From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
description: Comparison of mechanical ventilation incidence between intervention and control groups
measure: Biomarker levels (interleukin-6)
time frame: Baseline through post-treatment (6 days)
description: Comparison of mean biomarker level change between intervention and control groups. Units: pg/mL
measure: Biomarker levels (d-dimer)
time frame: Baseline through post-treatment (6 days)
description: Comparison of mean biomarker level change between intervention and control groups. Units: ug/mL
measure: Biomarker levels (lactate dehydrogenase)
time frame: Baseline through post-treatment (6 days)
description: Comparison of mean biomarker level change between intervention and control groups. Units: u/L
measure: Need for ECMO
time frame: From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
description: Comparison of ECMO incidence between intervention and control groups
measure: Major adverse cardiac events
time frame: From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
description: Compare frequency of major adverse cardiac events (MACE) between intervention and control groups
measure: Patient-reported functional status
time frame: Administered at 1, 3, 6, and 12 months post discharge (1 year)
description: Comparison of PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire results on a computer-adaptive platform between intervention and control groups using T-scores. Scale mean = 50, standard deviation = 10.
measure: PTSD Checklist
time frame: Administered at 1, 3, 6, and 12 months post discharge (1 year)
description: Patients will be administered a 20-question self-report measure of PTSD symptoms. Total scores range from 0-80. Scores of 31-33 or above generally indicate clinically likely PTSD.
arm group label: Intervention
arm group type: Experimental
description: 10ml intravenous hAF QD for 5 consecutive days
arm group label: Standard of Care
arm group type: No Intervention
description: 10 mL normal saline QD for 5 days
intervention type: Biological
intervention name: Human Amniotic Fluid
description: Patients will receive 10ml intravenous hAF each day for 5 consecutive days.
arm group label: Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Craig Selzman, MD
role: Principal Investigator
affiliation: University of Utah
last name: Craig Selzman, MD
phone: 8015815311
email: craig.selzman@hsc.utah.edu
last name: Alyssa Messina, MA
phone: 8015853752
email: alyssa.messina@hsc.utah.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Utah
investigator full name: Craig Selzman
investigator title: Principle Investigator
mesh term: COVID-19