Vadadustat for the Treatment of Nonintubated Acute Respir... | NCT07086755

Status Module

Name	Class
Akebia Therapeutics	INDUSTRY

Label	Type	Intervention Names
Vadadustat 900mg	Experimental	Drug: Vadadustat 900mg
Vadadustat 1200mg	Experimental	Drug: Vadadustat 1200mg
Placebo	Placebo Comparator	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Vadadustat 900mg	Drug	Participants will receive 900mg vadadustat (as oral tablets) for 14 days or until the date of discharge, whichever comes first, at approximately the same time each day without regard for timing of meals.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Win ratio for hierarchical composite endpoint based on death, duration of mechanical ventilation or ECMO, and duration of high-flow nasal oxygenation or non-invasive ventilation	The primary outcome is a hierarchical composite endpoint with 3 components: Death (yes or no); Duration of mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) in days; and Duration of high-flow nasal oxygenation (HFNO) or noninvasive ventilation (NIV) in days. Data will be reported as a Win Ratio, which quantifies the relative benefit of treatment compared to control. The Win Ratio is calculated from all pairwise comparisons of each patient in the treatment group compared with each patient in the control group, using the following formula: Win Ratio = Number of Wins/Number of Losses. Number of Wins is defined as: The count of pairs where the treatment group patient has a better outcome than the control group patient. Number of Losses is defined as: The count of pairs where the control group patient has a better outcome than the treatment group patient.	from the time of enrollment to 28 days after enrollment

Secondary Outcomes

Measure	Description	Time Frame
Number of deaths		from the time of enrollment to 28 days after enrollment
Duration of mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) in days		from the time of enrollment to 28 days after enrollment

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

-Meets the definition of nonintubated ARDS per the 2024 Global Definition of ARDS that includes all the following (2A-2D):

2A. Risk factors and origin of pulmonary edema: Precipitated by an acute predisposing risk factor, specifically from a suspected pathogen-associated etiology such as pneumonia* or non-pulmonary infection** [*Pneumonia defined as known or suspected based on treating physician documentation or discussion, OR both of the following criteria: 1) Chest radiography with new infiltrates, consolidation, or cavitation and (2) Clinical signs of pneumonia (new cough, sputum, fever, or white blood cells (WBC) > 12,000)] [**Non-pulmonary infection defined as suspected or proven infection meeting any of the following criteria: treating clinician suspects a viral, bacterial, or fungal infection, or cultures ordered in the past 24h or positive cultures within 1 week; or orders for antimicrobial medication.]
2B. Oxygenation: PaO2:FIO2 ≤ 300 mm Hg or SpO2:FIO2 ≤ 315 (if SpO2 ≤ 97%) on High-Flow Nasal Oxygen (HFNO) with flow of ≥ 30 L/min or non-invasive ventilation (NIV)/continuous positive airway pressure (CPAP) with at least 5 cm H2O end-expiratory pressure
2C. Timing: Acute onset or worsening of hypoxemic respiratory failure within 1 week of the estimated onset of the predisposing risk factor or new or worsening respiratory symptoms.
2D. Chest imaging: Chest infiltrates on radiography and computed tomography or B lines and/or consolidations on ultrasound not fully explained by effusions, atelectasis, or nodules/masses.

Exclusion Criteria:

Hypersensitivity to vadadustat or any of its excipients
Placed on mechanical ventilation before randomization
Patients on home oxygen therapy
Time since hospital admission order placed >72 hours
Hemoglobin above the gender-specific upper limit of normal (ULN) at randomization: 16 grams/deciliter (g/dL) for females and 18 g/dL for males
Patients with Aspartate transferase (AST) or Alanine aminotransferase (ALT) levels >5 times the upper limit of normal
Patients with AST or ALT levels >3 times the upper limit of normal along with a total bilirubin elevation of >2 times the upper limit of normal.
Patients who have erythrocytosis or polycythemia vera
Patients with uncontrolled hypertension
Patients with active malignancy
Patients with liver cirrhosis or active, acute liver disease
Patients taking erythropoiesis-stimulating agents
Patient taking probenecid, rifampicin, gemfibrozil, or teriflunomide
Women who are pregnant or breastfeeding, or positive pregnancy test before randomization
Patients who are prisoners
Patients who are currently enrolled in any other interventional clinical trial
Patients who have any prior history of arterial or venous thromboembolism within the past 3 months
Patients with a history of myocardial infarction, cerebrovascular event, or acute coronary syndrome within the past 3 months
Patients with known or suspected tuberculosis infection
Moribund patient not expected to survive 48 hours