Vadadustat for the Prevention and Treatment of Acute Resp... | NCT04478071

ID	Type	Description	Link
W81XWH-21-10032	Other Grant/Funding Number	United States Department of Defense

Status Module

Name	Class
Akebia Therapeutics	INDUSTRY
United States Department of Defense	FED

Label	Type	Description	Intervention Names
vadadustat	Experimental		Drug: vadadustat
placebo	Placebo Comparator		Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
vadadustat	Drug	Participants will receive vadadustat once daily for 14 days.	vadadustat

Outcomes Module

Primary Outcomes

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 Outcomes

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.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.

Other Outcomes

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)

Eligibility Module

Name	Affiliation	Role
Bentley J. Bobrow, MD	The University of Texas Health Science Center, Houston	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
The University of Texas Health Science Center at Houston		Houston	Texas	77030	United States

ID	Title	Description
FG000	Vadadustat	vadadustat: Participants will receive vadadustat once daily for 14 days.
FG001	Placebo	placebo: Participants will receive matching placebo once daily for 14 days.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 20, 2022

ID	Title	Description
BG000	Vadadustat	vadadustat: Participants will receive vadadustat once daily for 14 days.
BG001	Placebo	placebo: Participants will receive matching placebo once daily for 14 days.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000221 BG001227 BG002448

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

- ParticipantsBG000221
- ParticipantsBG001227
- ParticipantsBG002448

Title	Measurements

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Region of Enrollment

Number

participants

Title	Denominators	Categories
United States	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Number of Participants with history of type 2 diabetes

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Number of Participants with a history of hypertension

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Body Mass Index

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

Median

Inter-Quartile Range

kilograms per meter squared

Title	Denominators	Categories
	ParticipantsBG000218 ParticipantsBG001224 ParticipantsBG002

Days since onset of COVID symptoms

Data were not collected for 8 participants in the placebo arm. Data were not collected for 5 participants in the vadadustat arm.

Median

Inter-Quartile Range

days

Title	Denominators	Categories
	ParticipantsBG000216 ParticipantsBG001219 ParticipantsBG002

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.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.

Mean

Standard Deviation

score on a scale

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 Participants

Score on the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS)

NIAID-OS:

8 - Death 7 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation 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, limit on activities and/or requiring home oxygen 1 - Not hospitalized, no limits on activities

Mean

Standard Deviation

score on a scale

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001

Oxygen Saturation to Fraction of Inspired Oxygen (SpO2/FiO2) Ratio

SpO2 (oxygen saturation) is the percentage of oxygen in the blood. The fraction of inspired oxygen (FiO2) is the percentage of oxygen a person inhales.

Mean

Standard Deviation

SpO2/FiO2 Ratio

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 ParticipantsBG002

Score ≥ 4 on the Modified Sequential Organ Failure Assessment (MSOFA) Scale [1]

Modified Sequential Organ Failure Assessment (MSOFA) scale:

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000221 ParticipantsBG001227 Participants

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Posted

Count of Participants

Participants

day 14

ID	Title	Description
OG000	Vadadustat	vadadustat: Participants will receive vadadustat once daily for 14 days.
OG001	Placebo	placebo: Participants will receive matching placebo once daily for 14 days.

Units	Counts
Participants	OG000216 OG001223

Title

Denominators

Categories

Title	Measurements
	OG00043 OG00153

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Trial used Bayesian analysis for superiority. Hypothesis Testing for Primary Outcome: Among adult hospital admissions with lab-confirmed diagnosis of COVID-19, vadadustat 900 mg will demonstrate superiority to placebo as defined by a lower probability, at treatment day 14, of death (8) or hospitalization, on invasive mechanical ventilation or ECMO (7) or hospitalization, on non-invasive ventilation or high flow oxygen devices (6) on the NIAID-OS. See Statistical Analysis Plan for more details.					Risk Difference (RD)	-0.036			2-Sided	95	-0.084	0.009			Risk difference of Vadadustat relative to Placebo. Values under "confidence interval" reflect Bayesian 95% credible interval rather than frequentist confidence interval.

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:

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

Posted

Count of Participants

Participants

day 14

ID	Title	Description
OG000	Vadadustat	vadadustat: Participants will receive vadadustat once daily for 14 days.
OG001	Placebo	placebo: Participants will receive matching placebo once daily for 14 days.

Units	Counts
Participants	OG000

Other Pre-specified

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)

Not Posted

day 7

Participants

Other Pre-specified

Score on the Modified Sequential Organ Failure Assessment (MSOFA) Scale

Modified Sequential Organ Failure Assessment (MSOFA) scale:

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)

Not Posted

day 14

Participants

Other Pre-specified

Ventilator-free Survival

Not Posted

day 7

Participants

Other Pre-specified

Ventilator-free Survival

Not Posted

day 14

Participants

Other Pre-specified

Overall Survival

Not Posted

day 7

Participants

Other Pre-specified

Overall Survival

Not Posted

day 14

Participants

Other Pre-specified

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.

Not Posted

day 7

Participants

Other Pre-specified

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.

Not Posted

day 14

Participants

Other Pre-specified

Number of Participants With Acute Kidney Injury

Not Posted

day 7

Participants

Other Pre-specified

Number of Participants With Acute Kidney Injury

Not Posted

day 14

Participants

Other Pre-specified

Time to Hospital Discharge

Not Posted

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

Participants

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acute kidney injury	Investigations	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0003 events3 affected221 at risk EG0014 events4 affected227 at risk
Alanine aminotransferase and aspartate aminotransferase increased	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0012 events2 affected227 at risk
Alanine aminotransferase and aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0001 events1 affected221 at risk EG0012 events2 affected227 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0004 events4 affected221 at risk EG00110 events10 affected227 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected227 at risk
Atrial fibrillation with rapid ventricular response	Cardiac disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0014 events4 affected227 at risk
Bilateral pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Confusion	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Creatinine increased	Investigations	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Fungemia	Infections and infestations	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Gastric hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected227 at risk
Hemoglobin increased	Investigations	Systematic Assessment	EG0003 events3 affected221 at risk EG0012 events2 affected227 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Intermittent sinus pauses	Cardiac disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Non-ST elevation myocardial infarction type 2	Cardiac disorders	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0001 events1 affected221 at risk EG0012 events2 affected227 at risk
Septic shock	Infections and infestations	Systematic Assessment	EG00024 events24 affected221 at risk EG00125 events24 affected227 at risk
Thrombocytopenia	Investigations	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected227 at risk
Thromboembolic event	Vascular disorders	Systematic Assessment	EG0006 events6 affected221 at risk EG0013 events3 affected227 at risk
Worsening pneumonia	Infections and infestations	Systematic Assessment	EG00042 events42 affected221 at risk EG00159 events59 affected227 at risk
Worsening pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0012 events2 affected227 at risk
Arterial thromboembolism	Vascular disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Ascending cholangitis	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Atrial fibrillation and atrial flutter with rapid ventricular response	Cardiac disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Bilateral pneumothoraces	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Creatinine increased	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Deep vein thrombosis	Vascular disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Ejection fraction decreased due to dilated cardiomyopathy	Cardiac disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Neck abscess	Infections and infestations	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Platelet count decreased	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Pulmonary embolism	Vascular disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Severse sepsis with shock	Infections and infestations	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Staphylococcus aureus bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Thromboembolic event	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk
Transaminases increased	Investigations	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected227 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG00070 events69 affected221 at risk EG00151 events51 affected227 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG00030 events30 affected221 at risk EG00139 events38 affected227 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG00030 events30 affected221 at risk EG00133 events32 affected227 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment	EG00027 events24 affected221 at risk EG00121 events21 affected227 at risk
Hypermagnesemia	Metabolism and nutrition disorders	Systematic Assessment	EG00017 events17 affected221 at risk EG00134 events33 affected227 at risk
Hyperphosphatemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 events4 affected221 at risk EG00116 events16 affected227 at risk
Hypocalcemia	Metabolism and nutrition disorders	Systematic Assessment	EG00020 events19 affected221 at risk EG00120 events19 affected227 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG00019 events19 affected221 at risk EG00117 events17 affected227 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG00026 events24 affected221 at risk EG00135 events34 affected227 at risk

ID	Term
D012128	Respiratory Distress Syndrome
D018352	Coronavirus Infections
D000086382	COVID-19

ID	Term
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D012120	Respiration Disorders
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vadadustat	vadadustat: Participants will receive vadadustat once daily for 14 days.	19	221	61	221	109	221
EG001	Placebo	placebo: Participants will receive matching placebo once daily for 14 days.	19	227	73	227	116	227