CompletedNCT04478071Updated Mar 26, 2025Results posted

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

A Phase 2 interventional study of vadadustat and placebo in Acute Respiratory Distress Syndrome and Coronavirus Infection, sponsored by The University of Texas Health Science Center, Houston. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-26.

Sponsored by The University of Texas Health Science Center, Houston · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 448
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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).

Conditions studied

Acute Respiratory Distress Syndrome
Coronavirus Infection

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Keywords

COVID-19
ARDS

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 448 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

The University of Texas Health Science Center, Houston is the lead sponsor of 880 studies on the registry; 209 are open to participants now.

Of its 170 completed or terminated interventional studies of FDA-regulated products, 140 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 448 participants (actual)

Study arms

Experimental
vadadustat
Drug: vadadustat
Placebo comparator
placebo
Drug: placebo

Interventions

Drugvadadustat
Participants will receive vadadustat once daily for 14 days.
Also known as: AKB-6548
Drugplacebo
Participants will receive matching placebo once daily for 14 days.

What researchers measure

Primary outcomes

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
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
Time frame: day 14

Secondary outcomes

Number of Participants With a Total Score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale
Modified Sequential Organ Failure Assessment (MSOFA) scale: Each of 5 organ systems is given a score of 0 to 4.The MSOFA scale total score is the sum of the score for the 5 organ systems. Total score ranges from 0 to 20, a higher score indicates a worse outcome. Discharged patients will be assigned a score of 0 and dead patients a score of 20.
Time frame: day 14

Other outcomes

Score on the Modified Sequential Organ Failure Assessment (MSOFA) Scale
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)
Time frame: day 7
Score on the Modified Sequential Organ Failure Assessment (MSOFA) Scale
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)
Time frame: day 14
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
Hypotension is defined as Mean Arterial Pressure (MAP) \<70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.
Time frame: day 7
Number of Participants With Hypotension
Hypotension is defined as Mean Arterial Pressure (MAP) \<70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.
Time frame: day 14
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)

Results

Posted Mar 26, 2025

Participant flow

Participant flow — Overall Study
Milestone	Vadadustat	Placebo
Started	221	227
Completed day 7	217	223
Completed day 14	216	223
Completed day 28	215	221
Completed	215	221
Not completed	6	6

Outcome measures

PrimaryNumber 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

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

Time frame:: day 14
Reported as:: Count of participants · Participants

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
Participants	Vadadustat	Placebo
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	43	53

Statistical analysis

Vadadustat vs Placebo · Risk difference (rd): -0.036 · 95% CI -0.084 to 0.009Risk difference of Vadadustat relative to Placebo. Values under "confidence interval" reflect Bayesian 95% credible interval rather than frequentist confidence interval.
Vadadustat vs Placebo · Posterior probability: 0.94Posterior probability of the risk difference of Vadadustat relative to Placebo.

SecondaryNumber of Participants With a Total Score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale

Modified Sequential Organ Failure Assessment (MSOFA) scale: Each of 5 organ systems is given a score of 0 to 4.The MSOFA scale total score is the sum of the score for the 5 organ systems. Total score ranges from 0 to 20, a higher score indicates a worse outcome. Discharged patients will be assigned a score of 0 and dead patients a score of 20.

Time frame:: day 14
Reported as:: Count of participants · Participants

Number of Participants With a Total Score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale
Participants	Vadadustat	Placebo
Number of Participants With a Total Score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale	156	157

Statistical analysis

Vadadustat vs Placebo · Risk ratio (rr): 1.01 · 95% CI 0.92 to 1.1Risk ratio of Vadadustat relative to Placebo. Values under "confidence interval" reflect Bayesian 95% credible interval rather than frequentist confidence interval.
Vadadustat vs Placebo · Posterior probability: 0.57Posterior probability of the risk ratio of Vadadustat relative to Placebo.

Other pre-specifiedScore on the Modified Sequential Organ Failure Assessment (MSOFA) Scale

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)

Time frame:: day 7