Table 1.

Inclusion and exclusion criteria

Inclusion criteria 1. Moderate to severe ARDS as defined by the Berlin definition a. Onset within 1 week of identified insult. b. Within the same 24-h time period i. Hypoxic respiratory failure (PaO2/FiO2 ratio ≤ 27 kPa on PEEP ≥ 5 cm H20) ii. Bilateral infiltrates on chest X-ray consistent with pulmonary oedema not explained by another pulmonary pathology. iii. Respiratory failure not fully explained by cardiac failure or fluid overload. 2. The patient is receiving invasive mechanical ventilation. 3. In a separate COVID-19 cohort, COVID-19 based on clinical diagnosis or PCR test.

Exclusion criteria 1. More than 72 h from the onset of ARDS* 2. Age < 16 years 3. Patient is known to be pregnant 4. Major trauma in prior 5 days 5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year. 6. WHO Class III or IV pulmonary hypertension 7. Venous thromboembolism currently receiving anti-coagulation or within the past 3 months 8. Currently receiving extracorporeal life support (ECLS) 9. Severe chronic liver disease with Child-Pugh score > 12 10. DNAR (Do Not Attempt Resuscitation) order in place 11. Treatment withdrawal imminent within 24 h 12. Consent declined 13. Prisoners 14. Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available 15. Previously enrolled in the REALIST trial

*In phase 1, more than 48 h from the onset of ARDS