Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)

• ClinicalTrials.gov Identifier: NCT04478071
• Recruitment Status: Completed
• First Posted: July 20, 2020
• Last Update Posted: February 17, 2023
• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Akebia Therapeutics Inc.; United States Department of Defense
• Information provided by (Responsible Party): Bentley J. Bobrow, The University of Texas Health Science Center, Houston

Tracking Information

• First Submitted Date: July 15, 2020
• First Posted Date: July 20, 2020
• Last Update Posted Date: February 17, 2023
• Actual Study Start Date: August 22, 2020
• Actual Primary Completion Date: March 7, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 15, 2020)

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 ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 15, 2020)

Number of participants with a total score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) scale [ Time Frame: day 14 ]

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)

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 21, 2021)

• Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale [ Time Frame: day 7 ]
  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)
• Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale [ Time Frame: day 14 ]
  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)
• Ventilator-free survival [ Time Frame: day 7 ]
• Ventilator-free survival [ Time Frame: day 14 ]
• Overall survival [ Time Frame: day 7 ]
• Overall survival [ Time Frame: day 14 ]
• Number of participants with hypotension [ Time Frame: day 7 ]
  Hypotension is defined as Mean Arterial Pressure (MAP) <70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.
• Number of participants with hypotension [ Time Frame: day 14 ]
  Hypotension is defined as Mean Arterial Pressure (MAP) <70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.
• Number of participants with acute kidney injury [ Time Frame: day 7 ]
• Number of participants with acute kidney injury [ Time Frame: day 14 ]
• Time to hospital discharge [ Time Frame: From the time of hospital admission to hospital discharge (about 7 days) ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)
• Official Title: Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Acute Respiratory Distress Syndrome
• Coronavirus Infection

Intervention

• Drug: vadadustat
  Participants will receive vadadustat once daily for 14 days.
  Other Name: AKB-6548
• Drug: placebo
  Participants will receive matching placebo once daily for 14 days.

Study Arms

• Experimental: vadadustat
  Intervention: Drug: vadadustat
• Placebo Comparator: placebo
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 10, 2022): 449
• Original Estimated Enrollment (submitted: July 15, 2020): 300
• Actual Study Completion Date: March 7, 2022
• Actual Primary Completion Date: March 7, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Laboratory-confirmed diagnosis of COVID-19 by detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by Reverse transcription polymerase chain reaction (RT-PCR) from any specimen respiratory
• Admitted to the hospital within 36 hours
• Oxygen saturation of hemoglobin by pulse oximetry at room air ≤94%
• For patients admitted WITH respiratory symptoms, enrollment must occur within 36 hours of hospital admission. If the patient is admitted to the hospital with normal saturations, but develops respiratory symptoms DURING their hospital stay, enrollment may occur within 24 hours of desaturation to 94% or less on room air
• Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

• Hypersensitivity to vadadustat or any of its excipients
• Placed on mechanical ventilation before randomization
• Hemoglobin above the gender-specific upper limit of normal (ULN) at randomization: 16 g/dL for females and 18 g/dL for males
• Patients who have erythrocytosis or polycythemia vera
• Patient taking Probenecid, lopinavir or ritonavir
• Women who are pregnant or breastfeeding, or positive pregnancy test before randomization
• Patients not on maintenance dialysis with eGFC < 31 ml/min
• Patients who have received a solid organ transplant, heart, kidney, liver or lung
• Patients who are prisoners
• Patients who are currently Do Not Resuscitate (DNR) or Do Not Intubate (DNI)
• Patients with modified Rankin scale of 3 or greater
• Patient who are currently enrolled in any other interventional clinical trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04478071
• Other Study ID Numbers: HSC-MS-20-0395; W81XWH-21-10032 ( Other Grant/Funding Number: United States Department of Defense )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bentley J. Bobrow, The University of Texas Health Science Center, Houston
• Original Responsible Party: Same as current
• Current Study Sponsor: The University of Texas Health Science Center, Houston
• Original Study Sponsor: Same as current

Collaborators

• Akebia Therapeutics Inc.
• United States Department of Defense

Investigators

• Principal Investigator: Bentley J. Bobrow, MD; The University of Texas Health Science Center, Houston

• PRS Account: The University of Texas Health Science Center, Houston
• Verification Date: February 2023