Vadadustat for the Treatment of Nonintubated Acute Respiratory Distress Syndrome Due to Pathogen-Associated Lung Injury

Overview

The objective of this study is to assess the efficacy and safety of vadadustat for treating hospitalized patients with nonintubated Acute Respiratory Distress Syndrome (ARDS) secondary to pathogen-associated lung injury.

Interventions

• Drug Vadadustat 900mg
  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.
• Drug Vadadustat 1200mg
  Participants will receive 1200mg 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.
• Drug Placebo
  Participants will matching placebo (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.

Primary outcome measures

• 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 [Time frame: from the time of enrollment to 28 days after enrollment]

Secondary outcome measures (3)

• Number of deaths [Time frame: from the time of enrollment to 28 days after enrollment]
• Duration of mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) in days [Time frame: from the time of enrollment to 28 days after enrollment]
• Duration of high-flow nasal oxygenation (HFNO) or noninvasive ventilation (NIV) in days [Time frame: from the time of enrollment to 28 days after enrollment]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Texas Health Science Center at Houston — Houston

Identifiers

NCT: NCT07086755 · HSC-MS-22-0260

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗