Nonintubated Acute Respiratory Distress Syndrome (ARDS), Pathogen-associated Lung Injury
Conditions
Brief summary
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
DRUGVadadustat 900mg
Participants will receive 900mg vadadustat (as oral tablets) daily 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.
DRUGVadadustat 1200mg
Participants will receive 1200mg vadadustat (as oral tablets) daily 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.
DRUGPlacebo
Participants will matching placebo (as oral tablets) daily 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.
Sponsors
Paul Potnuru
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | from the time of enrollment to 28 days after enrollment | 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. |
Secondary
| Measure | 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 |
| Duration of high-flow nasal oxygenation (HFNO) or noninvasive ventilation (NIV) in days | from the time of enrollment to 28 days after enrollment |
Countries
United States
Contacts
CONTACTPaul Potnuru, MD
PRINCIPAL_INVESTIGATORPaul Potnuru, MD
The University of Texas Health Science Center, Houston
Outcome results
None listed