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

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04478071
• Other study ID #: HSC-MS-20-0395
• Secondary ID: W81XWH-21-10032
• Status: Completed
• Phase: Phase 2
• Start date: August 22, 2020
• Est. completion date: March 7, 2022

Study information

• Verified date: February 2023
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 449
• Est. completion date: March 7, 2022
• Est. primary completion date: March 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• vadadustat
Participants will receive vadadustat once daily for 14 days.
• placebo
Participants will receive matching placebo once daily for 14 days.

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	Akebia Therapeutics Inc., United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Ventilator-free survival		day 7
Other	Ventilator-free survival		day 14
Other	Overall survival		day 7
Other	Overall survival		day 14
Other	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
Other	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
Other	Number of participants with acute kidney injury		day 7
Other	Number of participants with acute kidney injury		day 14
Other	Time to hospital discharge		From the time of hospital admission to hospital discharge (about 7 days)
Primary	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	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