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

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).

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: vadadustat; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, 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)	day 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	day 14
Ventilator-free survival		day 7
Ventilator-free survival		day 14
Overall survival		day 7
Overall survival		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.	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.	day 14
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)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: United States Department of Defense; Akebia Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2020
• Primary Completion (Actual): March 7, 2022
• Study Completion (Actual): March 7, 2022

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; ARDS
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Coronavirus Infections; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: HSC-MS-20-0395; W81XWH-21-10032 (Other Grant/Funding Number: United States Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No