Trial Outcomes & Findings for Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) (NCT NCT04478071)

Last Updated: 2025-03-26

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

448 participants

Primary outcome timeframe

day 14

Results posted on

2025-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	Vadadustat vadadustat: Participants will receive vadadustat once daily for 14 days.	Placebo placebo: Participants will receive matching placebo once daily for 14 days.
Overall Study STARTED	221	227
Overall Study Completed Day 7	217	223
Overall Study Completed Day 14	216	223
Overall Study Completed Day 28	215	221
Overall Study COMPLETED	215	221
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Data were not collected for 3 participants in the placebo arm. Data were not collected for 3 participants in the vadadustat arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vadadustat n=221 Participants vadadustat: Participants will receive vadadustat once daily for 14 days.	Placebo n=227 Participants placebo: Participants will receive matching placebo once daily for 14 days.	Total n=448 Participants Total of all reporting groups
Age, Continuous	51.1 years STANDARD_DEVIATION 14.8 • n=221 Participants	50.7 years STANDARD_DEVIATION 14.7 • n=227 Participants	50.9 years STANDARD_DEVIATION 14.7 • n=448 Participants
Sex: Female, Male Female	79 Participants n=221 Participants	83 Participants n=227 Participants	162 Participants n=448 Participants
Sex: Female, Male Male	142 Participants n=221 Participants	144 Participants n=227 Participants	286 Participants n=448 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	158 Participants n=221 Participants	151 Participants n=227 Participants	309 Participants n=448 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=221 Participants	76 Participants n=227 Participants	139 Participants n=448 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=221 Participants	0 Participants n=227 Participants	0 Participants n=448 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=221 Participants	0 Participants n=227 Participants	0 Participants n=448 Participants
Race (NIH/OMB) Asian	13 Participants n=221 Participants	12 Participants n=227 Participants	25 Participants n=448 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=221 Participants	0 Participants n=227 Participants	0 Participants n=448 Participants
Race (NIH/OMB) Black or African American	21 Participants n=221 Participants	26 Participants n=227 Participants	47 Participants n=448 Participants
Race (NIH/OMB) White	168 Participants n=221 Participants	170 Participants n=227 Participants	338 Participants n=448 Participants
Race (NIH/OMB) More than one race	0 Participants n=221 Participants	0 Participants n=227 Participants	0 Participants n=448 Participants
Race (NIH/OMB) Unknown or Not Reported	19 Participants n=221 Participants	19 Participants n=227 Participants	38 Participants n=448 Participants
Region of Enrollment United States	221 participants n=221 Participants	227 participants n=227 Participants	448 participants n=448 Participants
Number of Participants with history of type 2 diabetes	62 Participants n=221 Participants	73 Participants n=227 Participants	135 Participants n=448 Participants
Number of Participants with a history of hypertension	74 Participants n=221 Participants	91 Participants n=227 Participants	165 Participants n=448 Participants
Body Mass Index	31.6 kilograms per meter squared n=218 Participants • Data were not collected for 3 participants in the placebo arm. Data were not collected for 3 participants in the vadadustat arm.	32.8 kilograms per meter squared n=224 Participants • Data were not collected for 3 participants in the placebo arm. Data were not collected for 3 participants in the vadadustat arm.	32.2 kilograms per meter squared n=442 Participants • Data were not collected for 3 participants in the placebo arm. Data were not collected for 3 participants in the vadadustat arm.
Days since onset of COVID symptoms	7 days n=216 Participants • Data were not collected for 8 participants in the placebo arm. Data were not collected for 5 participants in the vadadustat arm.	7 days n=219 Participants • Data were not collected for 8 participants in the placebo arm. Data were not collected for 5 participants in the vadadustat arm.	7 days n=435 Participants • Data were not collected for 8 participants in the placebo arm. Data were not collected for 5 participants in the vadadustat arm.
Score on the Modified Sequential Organ Failure Assessment (MSOFA) Scale	2.73 score on a scale STANDARD_DEVIATION 1.17 • n=221 Participants	2.74 score on a scale STANDARD_DEVIATION 1.19 • n=227 Participants	2.73 score on a scale STANDARD_DEVIATION 1.18 • n=448 Participants
Score on the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS)	5.3 score on a scale STANDARD_DEVIATION 0.5 • n=221 Participants	5.3 score on a scale STANDARD_DEVIATION 0.5 • n=227 Participants	5.3 score on a scale STANDARD_DEVIATION 0.5 • n=448 Participants
Oxygen Saturation to Fraction of Inspired Oxygen (SpO2/FiO2) Ratio	217.4 SpO2/FiO2 Ratio STANDARD_DEVIATION 91.8 • n=221 Participants	224.1 SpO2/FiO2 Ratio STANDARD_DEVIATION 94.2 • n=227 Participants	220.8 SpO2/FiO2 Ratio STANDARD_DEVIATION 93 • n=448 Participants
Score ≥ 4 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale [1]	69 Participants n=221 Participants	73 Participants n=227 Participants	142 Participants n=448 Participants

PRIMARY outcome

Timeframe: day 14

Outcome measures

Outcome measures
Measure	Vadadustat n=216 Participants vadadustat: Participants will receive vadadustat once daily for 14 days.	Placebo n=223 Participants placebo: Participants will receive matching placebo once daily for 14 days.
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 Participants	53 Participants

SECONDARY outcome

Timeframe: day 14

Population: Data were not collected for 2 participants in the vadadustat arm.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=214 Participants vadadustat: Participants will receive vadadustat once daily for 14 days.	Placebo n=223 Participants placebo: Participants will receive matching placebo once daily for 14 days.
Number of Participants With a Total Score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale	156 Participants	157 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 14

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 14

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 14

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7

Hypotension is defined as Mean Arterial Pressure (MAP) \<70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 14

Hypotension is defined as Mean Arterial Pressure (MAP) \<70 mm Hg or requirement for inotropes or vasopressors to maintain blood pressure.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 14

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From the time of hospital admission to hospital discharge (about 7 days)

Outcome measures

Outcome data not reported

Adverse Events

Vadadustat

Serious events: 61 serious events

Other events: 109 other events

Deaths: 19 deaths

Placebo

Serious events: 73 serious events

Other events: 116 other events

Deaths: 19 deaths

Serious adverse events

Serious adverse events
Measure	Vadadustat n=221 participants at risk vadadustat: Participants will receive vadadustat once daily for 14 days.	Placebo n=227 participants at risk placebo: Participants will receive matching placebo once daily for 14 days.
Investigations Acute kidney injury	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Renal and urinary disorders Acute kidney injury	1.4% 3/221 • Number of events 3 • up to 28 days	1.8% 4/227 • Number of events 4 • up to 28 days
Hepatobiliary disorders Alanine aminotransferase and aspartate aminotransferase increased	0.00% 0/221 • up to 28 days	0.88% 2/227 • Number of events 2 • up to 28 days
Investigations Alanine aminotransferase and aspartate aminotransferase increased	0.45% 1/221 • Number of events 1 • up to 28 days	0.88% 2/227 • Number of events 2 • up to 28 days
Investigations Alanine aminotransferase increased	1.8% 4/221 • Number of events 4 • up to 28 days	4.4% 10/227 • Number of events 10 • up to 28 days
Blood and lymphatic system disorders Anemia	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Cardiac disorders Atrial fibrillation	0.45% 1/221 • Number of events 1 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Cardiac disorders Atrial fibrillation with rapid ventricular response	0.00% 0/221 • up to 28 days	1.8% 4/227 • Number of events 4 • up to 28 days
Respiratory, thoracic and mediastinal disorders Bilateral pneumonia	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Psychiatric disorders Confusion	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Investigations Creatinine increased	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Infections and infestations Fungemia	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Gastrointestinal disorders Gastric hemorrhage	0.45% 1/221 • Number of events 1 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Investigations Hemoglobin increased	1.4% 3/221 • Number of events 3 • up to 28 days	0.88% 2/227 • Number of events 2 • up to 28 days
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Cardiac disorders Intermittent sinus pauses	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Cardiac disorders Non-ST elevation myocardial infarction type 2	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Infections and infestations Pneumonia	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Infections and infestations Sepsis	0.45% 1/221 • Number of events 1 • up to 28 days	0.88% 2/227 • Number of events 2 • up to 28 days
Infections and infestations Septic shock	10.9% 24/221 • Number of events 24 • up to 28 days	10.6% 24/227 • Number of events 25 • up to 28 days
Investigations Thrombocytopenia	0.00% 0/221 • up to 28 days	0.44% 1/227 • Number of events 1 • up to 28 days
Vascular disorders Thromboembolic event	2.7% 6/221 • Number of events 6 • up to 28 days	1.3% 3/227 • Number of events 3 • up to 28 days
Infections and infestations Worsening pneumonia	19.0% 42/221 • Number of events 42 • up to 28 days	26.0% 59/227 • Number of events 59 • up to 28 days
Respiratory, thoracic and mediastinal disorders Worsening pneumonia	0.45% 1/221 • Number of events 1 • up to 28 days	0.88% 2/227 • Number of events 2 • up to 28 days
Vascular disorders Arterial thromboembolism	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Hepatobiliary disorders Ascending cholangitis	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Investigations Aspartate aminotransferase increased	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Cardiac disorders Atrial fibrillation and atrial flutter with rapid ventricular response	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Respiratory, thoracic and mediastinal disorders Bilateral pneumothoraces	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Cardiac disorders Cardiac arrest	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Renal and urinary disorders Creatinine increased	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Vascular disorders Deep vein thrombosis	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Cardiac disorders Ejection fraction decreased due to dilated cardiomyopathy	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Infections and infestations Neck abscess	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Blood and lymphatic system disorders Platelet count decreased	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Vascular disorders Pulmonary embolism	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Infections and infestations Severse sepsis with shock	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Infections and infestations Staphylococcus aureus bacteremia	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Blood and lymphatic system disorders Thromboembolic event	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days
Investigations Transaminases increased	0.45% 1/221 • Number of events 1 • up to 28 days	0.00% 0/227 • up to 28 days

Other adverse events

Other adverse events
Measure	Vadadustat n=221 participants at risk vadadustat: Participants will receive vadadustat once daily for 14 days.	Placebo n=227 participants at risk placebo: Participants will receive matching placebo once daily for 14 days.
Investigations Alanine aminotransferase increased	31.2% 69/221 • Number of events 70 • up to 28 days	22.5% 51/227 • Number of events 51 • up to 28 days
Blood and lymphatic system disorders Anemia	13.6% 30/221 • Number of events 30 • up to 28 days	16.7% 38/227 • Number of events 39 • up to 28 days
Investigations Aspartate aminotransferase increased	13.6% 30/221 • Number of events 30 • up to 28 days	14.1% 32/227 • Number of events 33 • up to 28 days
Metabolism and nutrition disorders Hyperkalemia	10.9% 24/221 • Number of events 27 • up to 28 days	9.3% 21/227 • Number of events 21 • up to 28 days
Metabolism and nutrition disorders Hypermagnesemia	7.7% 17/221 • Number of events 17 • up to 28 days	14.5% 33/227 • Number of events 34 • up to 28 days
Metabolism and nutrition disorders Hyperphosphatemia	1.8% 4/221 • Number of events 4 • up to 28 days	7.0% 16/227 • Number of events 16 • up to 28 days
Metabolism and nutrition disorders Hypocalcemia	8.6% 19/221 • Number of events 20 • up to 28 days	8.4% 19/227 • Number of events 20 • up to 28 days
Metabolism and nutrition disorders Hypokalemia	8.6% 19/221 • Number of events 19 • up to 28 days	7.5% 17/227 • Number of events 17 • up to 28 days
Metabolism and nutrition disorders Hyponatremia	10.9% 24/221 • Number of events 26 • up to 28 days	15.0% 34/227 • Number of events 35 • up to 28 days

Additional Information

Bentley J. Bobrow, MD

The University of Texas Health Science Center at Houston

Phone: 713-500-7863

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place