NCT04478071

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

Completed Phase 2 Results posted Last updated 26 March 2025

What this trial tests

Phase 2 trial testing vadadustat in Acute Respiratory Distress Syndrome in 448 participants. Completed in 25 March 2022.

Timeline

22 August 2020

Primary endpoint
7 March 2022

25 March 2022

Quick facts

Lead sponsor	The University of Texas Health Science Center, Houston
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	448
Start date	22 August 2020
Primary completion	7 March 2022
Estimated completion	25 March 2022
Sites	1 location across United States

Drugs / interventions tested

• vadadustat — full drug profile →
• placebo

Conditions studied

• Acute Respiratory Distress Syndrome — all drugs for Acute Respiratory Distress Syndrome →
• Coronavirus Infection — all drugs for Coronavirus Infection →

Sponsor

The University of Texas Health Science Center, Houston

Who can join

18 and older, any sex, with Acute Respiratory Distress Syndrome or Coronavirus Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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 h

Group	Value	95% CI
Vadadustat	43
Placebo	53

Number of Participants With a Total Score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale Secondary · day 14

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.

Group	Value	95% CI
Vadadustat	156
Placebo	157

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 28 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vadadustat

Serious: 61/221 (28%)

Deaths: 19/221

Placebo

Serious: 73/227 (32%)

Deaths: 19/227

Serious adverse events (40 terms)

Reaction	System	Vadadustat	Placebo
Worsening pneumonia	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Thromboembolic event	Vascular disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Atrial fibrillation with rapid ventricular response	Cardiac disorders	—	—
Hemoglobin increased	Investigations	—	—
Alanine aminotransferase and aspartate aminotransferase increased	Hepatobiliary disorders	—	—
Alanine aminotransferase and aspartate aminotransferase increased	Investigations	—	—
Sepsis	Infections and infestations	—	—
Worsening pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Acute kidney injury	Investigations	—	—
Anemia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Bilateral pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Confusion	Psychiatric disorders	—	—
Creatinine increased	Investigations	—	—
Fungemia	Infections and infestations	—	—
Gastric hemorrhage	Gastrointestinal disorders	—	—
Hyperkalemia	Metabolism and nutrition disorders	—	—
Intermittent sinus pauses	Cardiac disorders	—	—
Non-ST elevation myocardial infarction type 2	Cardiac disorders	—	—
Pneumonia	Infections and infestations	—	—
Thrombocytopenia	Investigations	—	—
Arterial thromboembolism	Vascular disorders	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Vadadustat	Placebo
Alanine aminotransferase increased	Investigations	—	—
Anemia	Blood and lymphatic system disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Hypermagnesemia	Metabolism and nutrition disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Hyperkalemia	Metabolism and nutrition disorders	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Hyperphosphatemia	Metabolism and nutrition disorders	—	—

Most-reported serious reactions: Worsening pneumonia, Septic shock, Alanine aminotransferase increased, Thromboembolic event, Acute kidney injury, Atrial fibrillation with rapid ventricular response, Hemoglobin increased, Alanine aminotransferase and aspartate aminotransferase increased.

Data from ClinicalTrials.gov NCT04478071 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.
   Yuan X, Ruan W, Bobrow B, Carmeliet P, et al · · 2024 · cited 144× · PMID 38123660 · DOI 10.1038/s41573-023-00848-6
2. Mechanisms of Endothelial Regeneration and Vascular Repair and Their Application to Regenerative Medicine.
   Evans CE, Iruela-Arispe ML, Zhao YY. · · 2021 · cited 126× · PMID 33069720 · DOI 10.1016/j.ajpath.2020.10.001
3. Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management.
   Aslan A, Aslan C, Zolbanin NM, Jafari R. · · 2021 · cited 92× · PMID 34872623 · DOI 10.1186/s41479-021-00092-9
4. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.
   Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, et al · · 2024 · cited 73× · PMID 38295575 · DOI 10.1016/j.redox.2024.103049
5. Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury.
   Li X, Berg NK, Mills T, Zhang K, et al · · 2020 · cited 39× · PMID 33519814 · DOI 10.3389/fimmu.2020.604944
6. Targeting alveolar-specific succinate dehydrogenase A attenuates pulmonary inflammation during acute lung injury.
   Vohwinkel CU, Coit EJ, Burns N, Elajaili H, et al · · 2021 · cited 27× · PMID 33687752 · DOI 10.1096/fj.202002778r
7. Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.
   Wing PAC, Prange-Barczynska M, Cross A, Crotta S, et al · · 2022 · cited 25× · PMID 36067210 · DOI 10.1371/journal.ppat.1010807
8. HIF1A-dependent induction of alveolar epithelial PFKFB3 dampens acute lung injury.
   Vohwinkel CU, Burns N, Coit E, Yuan X, et al · · 2022 · cited 24× · PMID 36326834 · DOI 10.1172/jci.insight.157855