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

Bentley J. Bobrow

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Pathogen-associated Lung Injury; Nonintubated Acute Respiratory Distress Syndrome (ARDS)

Treatments: Drug: Vadadustat 900mg; Drug: Vadadustat 1200mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07086755

HSC-MS-22-0260

Details and patient eligibility

About

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.

Enrollment: 1,100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,100 participants in 3 patient groups, including a placebo group

Vadadustat 900mg

Experimental group

Treatment:

Drug: Vadadustat 900mg

Vadadustat 1200mg

Experimental group

Treatment:

Drug: Vadadustat 1200mg

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo