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

Sponsor

The University of Texas Health Science Center, Houston (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04478071

Collaborator

Akebia Therapeutics Inc. (Other), United States Department of Defense (U.S. Fed)

449

Enrollment

Location

Arms

19.6

Anticipated Duration (Months)

22.9

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome Coronavirus Infection	Drug: vadadustat Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

449 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 22, 2020

Actual Primary Completion Date :

Feb 16, 2022

Anticipated Study Completion Date :

Apr 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vadadustat	Drug: vadadustat Participants will receive vadadustat once daily for 14 days. Other Names: AKB-6548
Placebo Comparator: placebo	Drug: placebo Participants will receive matching placebo once daily for 14 days.

Arm

Intervention/Treatment

Experimental: vadadustat

Drug: vadadustat

Participants will receive vadadustat once daily for 14 days.

Other Names:

AKB-6548

Placebo Comparator: placebo

Drug: placebo

Participants will receive matching placebo once daily for 14 days.

Outcome Measures

Primary Outcome Measures

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 [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

Secondary Outcome Measures

Number of participants with a total score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) scale [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)

Other Outcome Measures

Score on the Modified Sequential Organ Failure Assessment (MSOFA) scale [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 [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 [day 7]
Ventilator-free survival [day 14]
Overall survival [day 7]
Overall survival [day 14]
Number of participants with hypotension [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 [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 [day 7]
Number of participants with acute kidney injury [day 14]
Time to hospital discharge [From the time of hospital admission to hospital discharge (about 7 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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