Vadadustat for nonintubated ARDS caused by infection

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

This study tests if vadadustat can help hospitalized patients with nonintubated ARDS from infection breathe better and avoid needing a ventilator.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 1100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The University of Texas Health Science Center, Houston (other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07086755 on ClinicalTrials.gov

What this trial studies

Hospitalized patients with nonintubated ARDS attributed to a suspected pathogen-associated lung injury are assigned to receive one of two doses of oral vadadustat or placebo. The combined Phase 2/Phase 3 design examines dosing, clinical efficacy, and safety signals. Key outcomes include oxygenation (PaO2:FiO2), progression to mechanical ventilation, clinical status, and adverse events. The trial is led at The University of Texas Health Science Center at Houston in collaboration with Akebia Therapeutics.

Who should consider this trial

Good fit: Ideal candidates are hospitalized adults who meet the 2024 definition of nonintubated ARDS with PaO2:FiO2 ≤ 300 mm Hg and suspected or confirmed pathogen-associated lung injury such as pneumonia or non-pulmonary infection.

Not a fit: Patients who are already intubated, who do not have infection-associated lung injury, or who have contraindications to vadadustat may not receive benefit from this intervention.

Why it matters

Potential benefit: If successful, vadadustat could improve oxygenation and reduce the need for mechanical ventilation in patients with infection-related nonintubated ARDS.

How similar studies have performed: Vadadustat has established use in anemia of chronic kidney disease, but using it to treat ARDS is novel and prior clinical evidence in this indication is limited.

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

Where this trial is running

Houston, Texas

• The University of Texas Health Science Center at Houston — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Paul Potnuru, MD — The University of Texas Health Science Center, Houston
• Study coordinator: Paul Potnuru, MD

Conditions: Nonintubated Acute Respiratory Distress Syndrome, Pathogen-associated Lung Injury