<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/NCT04478071</url>
  </required_header>
  <id_info>
    <org_study_id>HSC-MS-20-0395</org_study_id>
    <secondary_id>W81XWH-21-10032</secondary_id>
    <nct_id>NCT04478071</nct_id>
  </id_info>
  <brief_title>Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)</brief_title>
  <official_title>Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center, Houston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Akebia Therapeutics Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Health Science Center, Houston</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy of vadadustat for the prevention and&#xD;
      treatment of acute respiratory distress syndrome (ARDS) in hospitalized patients with&#xD;
      Coronavirus Disease 2019 (COVID-19).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 22, 2020</start_date>
  <completion_date type="Actual">March 7, 2022</completion_date>
  <primary_completion_date type="Actual">March 7, 2022</primary_completion_date>
  <phase>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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants who are classified 8 (dead), 7 (hospitalized, on invasive mechanical ventilation or ECMO), or 6 (hospitalized, on non-invasive ventilation or high flow oxygen devices) on the NIAID ordinal scale</measure>
    <time_frame>day 14</time_frame>
    <description>National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS):&#xD;
8 - Death 7 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 6 - Hospitalized, on non-invasive ventilation or high flow oxygen devices 5 - Hospitalized, requiring supplemental oxygen 4 - Hospitalized, not requiring supplemental oxygen - requiring ongoing care (COVID-19 related or otherwise) 3 - Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 2 - Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
1 - Not hospitalized, no limitations on activities</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with a total score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) scale</measure>
    <time_frame>day 14</time_frame>
    <description>Modified Sequential Organ Failure Assessment (MSOFA) scale:&#xD;
Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20.&#xD;
Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (&gt; 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150)&#xD;
Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice)&#xD;
Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP &lt; 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine &gt; 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine &gt; 15, Epinephrine &gt; 0.1, Norepinephrine &gt; 0.1)&#xD;
Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (&lt; 6)&#xD;
Renal, Creatinine mg/dL: 0 (&lt; 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (&gt; 5.0)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale</measure>
    <time_frame>day 7</time_frame>
    <description>Modified Sequential Organ Failure Assessment (MSOFA) scale:&#xD;
Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20.&#xD;
Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (&gt; 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150)&#xD;
Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice)&#xD;
Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP &lt; 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine &gt; 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine &gt; 15, Epinephrine &gt; 0.1, Norepinephrine &gt; 0.1)&#xD;
Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (&lt; 6)&#xD;
Renal, Creatinine mg/dL: 0 (&lt; 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (&gt; 5.0)</description>
  </other_outcome>
  <other_outcome>
    <measure>Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale</measure>
    <time_frame>day 14</time_frame>
    <description>Modified Sequential Organ Failure Assessment (MSOFA) scale:&#xD;
Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20.&#xD;
Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (&gt; 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150)&#xD;
Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice)&#xD;
Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP &lt; 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine &gt; 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine &gt; 15, Epinephrine &gt; 0.1, Norepinephrine &gt; 0.1)&#xD;
Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (&lt; 6)&#xD;
Renal, Creatinine mg/dL: 0 (&lt; 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (&gt; 5.0)</description>
  </other_outcome>
  <other_outcome>
    <measure>Ventilator-free survival</measure>
    <time_frame>day 7</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Ventilator-free survival</measure>
    <time_frame>day 14</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>day 7</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>day 14</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with hypotension</measure>
    <time_frame>day 7</time_frame>
    <description>Hypotension is defined as Mean Arterial Pressure (MAP) &lt;70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with hypotension</measure>
    <time_frame>day 14</time_frame>
    <description>Hypotension is defined as Mean Arterial Pressure (MAP) &lt;70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with acute kidney injury</measure>
    <time_frame>day 7</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with acute kidney injury</measure>
    <time_frame>day 14</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to hospital discharge</measure>
    <time_frame>From the time of hospital admission to hospital discharge (about 7 days)</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">449</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <condition>Coronavirus Infection</condition>
  <arm_group>
    <arm_group_label>vadadustat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vadadustat</intervention_name>
    <description>Participants will receive vadadustat once daily for 14 days.</description>
    <arm_group_label>vadadustat</arm_group_label>
    <other_name>AKB-6548</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Participants will receive matching placebo once daily for 14 days.</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Laboratory-confirmed diagnosis of COVID-19 by detection of severe acute respiratory&#xD;
             syndrome coronavirus 2 (SARS-CoV-2) RNA by Reverse transcription polymerase chain&#xD;
             reaction (RT-PCR) from any specimen respiratory&#xD;
&#xD;
          -  Admitted to the hospital within 36 hours&#xD;
&#xD;
          -  Oxygen saturation of hemoglobin by pulse oximetry at room air ≤94%&#xD;
&#xD;
          -  For patients admitted WITH respiratory symptoms, enrollment must occur within 36 hours&#xD;
             of hospital admission. If the patient is admitted to the hospital with normal&#xD;
             saturations, but develops respiratory symptoms DURING their hospital stay, enrollment&#xD;
             may occur within 24 hours of desaturation to 94% or less on room air&#xD;
&#xD;
          -  Understands the procedures and requirements of the study and provides written informed&#xD;
             consent and authorization for protected health information disclosure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to vadadustat or any of its excipients&#xD;
&#xD;
          -  Placed on mechanical ventilation before randomization&#xD;
&#xD;
          -  Hemoglobin above the gender-specific upper limit of normal (ULN) at randomization: 16&#xD;
             g/dL for females and 18 g/dL for males&#xD;
&#xD;
          -  Patients who have erythrocytosis or polycythemia vera&#xD;
&#xD;
          -  Patient taking Probenecid, lopinavir or ritonavir&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding, or positive pregnancy test before&#xD;
             randomization&#xD;
&#xD;
          -  Patients not on maintenance dialysis with eGFC &lt; 31 ml/min&#xD;
&#xD;
          -  Patients who have received a solid organ transplant, heart, kidney, liver or lung&#xD;
&#xD;
          -  Patients who are prisoners&#xD;
&#xD;
          -  Patients who are currently Do Not Resuscitate (DNR) or Do Not Intubate (DNI)&#xD;
&#xD;
          -  Patients with modified Rankin scale of 3 or greater&#xD;
&#xD;
          -  Patient who are currently enrolled in any other interventional clinical trial&#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>Bentley J. Bobrow, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas Health Science Center, Houston</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <disposition_first_submitted>February 14, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>February 14, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 17, 2023</disposition_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Texas Health Science Center, Houston</investigator_affiliation>
    <investigator_full_name>Bentley J. Bobrow</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>ARDS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04478071
org study id: HSC-MS-20-0395
secondary id: W81XWH-21-10032
nct id: NCT04478071
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy of vadadustat for the prevention and
      treatment of acute respiratory distress syndrome (ARDS) in hospitalized patients with
      Coronavirus Disease 2019 (COVID-19).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants who are classified 8 (dead), 7 (hospitalized, on invasive mechanical ventilation or ECMO), or 6 (hospitalized, on non-invasive ventilation or high flow oxygen devices) on the NIAID ordinal scale
time frame: day 14
description: National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS):
8 - Death 7 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 6 - Hospitalized, on non-invasive ventilation or high flow oxygen devices 5 - Hospitalized, requiring supplemental oxygen 4 - Hospitalized, not requiring supplemental oxygen - requiring ongoing care (COVID-19 related or otherwise) 3 - Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 2 - Not hospitalized, limitation on activities and/or requiring home oxygen
1 - Not hospitalized, no limitations on activities
measure: Number of participants with a total score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) scale
time frame: day 14
description: Modified Sequential Organ Failure Assessment (MSOFA) scale:
Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20.
Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (> 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150)
Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice)
Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP < 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine > 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine > 15, Epinephrine > 0.1, Norepinephrine > 0.1)
Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (< 6)
Renal, Creatinine mg/dL: 0 (< 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (> 5.0)
measure: Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale
time frame: day 7
description: Modified Sequential Organ Failure Assessment (MSOFA) scale:
Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20.
Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (> 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150)
Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice)
Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP < 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine > 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine > 15, Epinephrine > 0.1, Norepinephrine > 0.1)
Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (< 6)
Renal, Creatinine mg/dL: 0 (< 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (> 5.0)
measure: Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale
time frame: day 14
description: Modified Sequential Organ Failure Assessment (MSOFA) scale:
Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20.
Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (> 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150)
Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice)
Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP < 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine > 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine > 15, Epinephrine > 0.1, Norepinephrine > 0.1)
Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (< 6)
Renal, Creatinine mg/dL: 0 (< 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (> 5.0)
measure: Ventilator-free survival
time frame: day 7
measure: Ventilator-free survival
time frame: day 14
measure: Overall survival
time frame: day 7
measure: Overall survival
time frame: day 14
measure: Number of participants with hypotension
time frame: day 7
description: Hypotension is defined as Mean Arterial Pressure (MAP) <70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.
measure: Number of participants with hypotension
time frame: day 14
description: Hypotension is defined as Mean Arterial Pressure (MAP) <70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.
measure: Number of participants with acute kidney injury
time frame: day 7
measure: Number of participants with acute kidney injury
time frame: day 14
measure: Time to hospital discharge
time frame: From the time of hospital admission to hospital discharge (about 7 days)
arm group label: vadadustat
arm group type: Experimental
arm group label: placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: vadadustat
description: Participants will receive vadadustat once daily for 14 days.
arm group label: vadadustat
other name: AKB-6548
intervention type: Drug
intervention name: placebo
description: Participants will receive matching placebo once daily for 14 days.
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bentley J. Bobrow, MD
role: Principal Investigator
affiliation: The University of Texas Health Science Center, Houston
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The University of Texas Health Science Center, Houston
investigator full name: Bentley J. Bobrow
investigator title: Professor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
sharing ipd: No