Acute respiratory distress syndrome

Inclusion Criteria

- ≥18 years of age at the time of inclusion into study.

- Invasively mechanically ventilated acute respiratory distress syndrome [ARDS] patients (diagnosed according to Berlin definition of ARDS, including positive end-expiratory pressure [PEEP] of ≥5 cm H2O, X-ray (or CT scan) indicative of ARDS: bilateral opacities not fully explained by cardiac failure, fluid overload, lobar/lung collapse, effusions or nodules).

- Initial diagnosis of mild, moderate or severe ARDS prior to study inclusion, with acute onset of ARDS within 1 week after suspected trigger factor of

-- Pneumonia

-- Aspiration

-- Sepsis

-- Pancreatitis

- Prior to randomization, hypoxemia with PaO2:FiO2 ≤300 mmHg continuously observed for a period of ≥4 hours (with values of ≥2 arterial blood gas [ABG] analyses during that time, with the last value obtained timely (generally ≤3 hours) prior to randomization), under ventilation with minimum PEEP ≥8 cm H2O.

- Time from first meeting the last diagnostic ARDS criterion (Berlin criteria) to randomization must be ≤48 hours.

- For Study Part A: ARDS patients for whom measurements of extra-vascular lung water are regarded as medically indicated by the treating physician, and these measurements are planned as part of their clinical care, from Study Day 1 up to Study Day 7 (if then still intubated).

Exclusion Criteria

- Any value of a PaO2:FiO2 ratio >300 mmHg within a time interval of 4 hours before randomization

- Rescue therapy (e.g. inhalation of nitric oxide gas and/or inhalation of prostacyclin analogues, or extra corporeal membrane oxygenation [ECMO] / extra corporeal CO2 removal [ECCO2R]) already initiated at screening and/or Study Day 1 (prior to first dose of the study intervention)

- Moribund participants not expected to survive 24 hours (clinical decision)

- Expected duration of invasive mechanical ventilation less than 48 hours (clinical decision)

- History of co-morbidities requiring long-term/home oxygen use (e.g. severe chronic obstructive pulmonary disease [COPD], pulmonary fibrosis) or non-invasive ventilation (except for sleep apnea management), or making weaning per se improbable (e.g. ALS, muscular dystrophy)

- Smoke inhalation injury, extensive burns or trauma/head injury as concomitant condition

- History of pneumectomy, lung lobectomy or lung transplant

- Diffuse alveolar hemorrhage from vasculitis

- Current lung malignancy (incl. lung metastasis), or other malignancy requiring chemotherapy or radiation within the last month

- Chronic kidney disease with a history of renal replacement therapy (e.g. dialysis)

- Chronic liver disease Child-Pugh Class C

- Chronic heart failure NYHA IV

- Known hypersensitivity to polyethyleneglycol (PEG, Macrogol)

- Participation in other interventional studies involving pharmacological interventions, or biological or cell therapy interventions

- Diagnosis of COVID-19 pneumonia within 6 weeks prior to study inclusion. History of SARS-CoV-2 infection (positive test based on nucleic acid amplification technology or positive antigen test) without COVID-19 pneumonia does not exclude patients