Sivelestat for Acute Respiratory Distress Syndrome Due to COVID-19

Inclusion Criteria:

• Age ≥18 years old
• Confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR) insputum, nasopharyngeal swabs, or oropharyngeal swabs
• Diagnosis of acute respiratory distress syndrome (ARDS) according to the BerlinDefinition criteria
• Onset of ARDS less than 72 hours before randomization
• Written informed consent

Exclusion Criteria:

• ARDS potentially caused by extra-pulmonary reasons, including non-pulmonary sepsis,pancreatitis, multiple trauma and massive transfusion, etc.
• Leukopenia (leukocyte count <4,000/μL/) and/or thrombocytopenia (platelet count <100,000/μL)
• Significant hepatic dysfunction, defined as elevated AST and ALT ≥ 3 times the normallimits, or total bilirubin ≥ 1.5 mg/dL
• Severe renal insufficiency with serum creatinine > 3.0 mg/dL
• History of moderate to severe chronic lung disease requiring home-based oxygentherapy, including chronic obstructive pulmonary disease (COPD), interstitial lungdisease (ILD), asthma and bronchiectasis, etc.
• Pre-existing peripheral nerve injury, spinal cord trauma, or neuromuscular disorderthat may impair spontaneous ventilation (e.g., high cervical spinal cord injury,Guillain-Barré Syndrome, and myasthenia gravis, etc.)
• Current diagnosis of pulmonary embolism
• Coexisting multi-organ failure, affecting more than 3 systems
• Combined with burn injury
• Life expectancy less than 6 months (e.g., due to an an end-stage malignant disease)
• Moribund and expected to die within 48 hours
• Known allergy to sivelestat or any of the study drug excipients
• Pregnancy or lactation, or the possibility of conception
• Current or recent (last 3 months) participation in any other clinical trial