1. Persistent septic shock (>24h) with a Mean Arterial Pressure (MAP) ≤ 65 mm Hg and serum lactate level > 4 mmol/L (36 mg/dL) despite adequate volume resuscitation and vasopressor use (norepinephrine > 0.2 μg/kg/min) for > 6 hours, 2. Pre-existing chronic pulmonary disease, including: o Known diagnosis of Interstitial Lung disease o Known diagnosis of COPD Gold IV or FEV1<30%pred o DLCO <45% (if test results are available) o Total lung capacity (TLC) < 60% of predicted (if test results are available), 3. Chronic home oxygen treatment, 4. Pre-existing heart failure with a known left ventricular ejection fraction <40%, 5. Active treatment of haematological or non-haematological cancer with targeted immuno- or chemotherapy, or thoracic radiotherapy in the last year, 6. Currently receiving extracorporeal life support (ECLS), 7. Severe chronic liver disease with Child-Pugh score > 12, 8. Subjects in whom a decision to withdraw medical care is made (e.g. palliative setting), 9. Inability of the ICU staff to initiate study drug administration within 48 hours of screening, 10. Known to be pregnant or breast-feeding, 11. Enrolled in a concomitant clinical trial of an investigational medicinal product, 12. White blood count < 2.5x109/l, 13. Haemoglobin < 4.0 mmol/l, 14. Thrombocytes < 50x109/l, 15. The use of strong CYP3A4 inducers, including the following drugs: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine, 1. Persisterende septische shock (>24 uur) met Mean Arterial Pressure (MAP) ≤ 65 mm Hg en serum lactaat > 4 mmol/L (36 mg/dL) ondanks adequate volume resuscitatie en vasopressie (noradrenaline > 0.2 μg/kg/min) voor > 6 uur, 2. Pre-existente chronische longziekte, inclusief: o Interstitiele longziekte o COPD Gold IV of FEV1<30% of predicted o DLCO <45% (indien bekend) o Total lung capacity (TLC) < 60% of predicted (indien bekend) 3. Chronische zuurstof therapie thuis 4. Pre-existent hartfalen met ventriculaire ejectie fractie <40%, 5. Active behandeling voor hematologische of niet-hematologische maligniteit met immuno- of chemotherapie, of thoracale radiotherapie in het laatste jaar, 6. Patiënt ondergaat extracorporeal life support (ECLS), 7. Ernstige chronische leverziekte (Child-Pugh score > 12), 8. Patiënten met een palliatief beleid, 9. Onvermogen van de IC staf om behandeling met de studiemedicatie binnen 48 uur na screening te starten 10. Patiënte is zwanger of geeft borstvoeding, 11. Patiënt is reeds in een andere medicijnenstudie geincludeerd, 12. Leukocyten < 2.5x109/l, 13. Hemoglobine < 4.0 mmol/l, 14. Trombocyten < 50x109/l, 15. Gebruik van sterke CYP3A4 inductoren, inclusief: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine,

1. Persistent septic shock (>24h) with a Mean Arterial Pressure (MAP) ≤ 65 mm Hg and serum lactate level > 4 mmol/L (36 mg/dL) despite adequate volume resuscitation and vasopressor use (norepinephrine > 0.2 μg/kg/min) for > 6 hours, 2. Pre-existing chronic pulmonary disease, including: o Known diagnosis of Interstitial Lung disease o Known diagnosis of COPD Gold IV or FEV1<30%pred o DLCO <45% (if test results are available) o Total lung capacity (TLC) < 60% of predicted (if test results are available), 3. Chronic home oxygen treatment, 4. Pre-existing heart failure with a known left ventricular ejection fraction <40%, 5. Active treatment of haematological or non-haematological cancer with targeted immuno- or chemotherapy, or thoracic radiotherapy in the last year, 6. Currently receiving extracorporeal life support (ECLS), 7. Severe chronic liver disease with Child-Pugh score > 12, 8. Subjects in whom a decision to withdraw medical care is made (e.g. palliative setting), 9. Inability of the ICU staff to initiate study drug administration within 48 hours of screening, 10. Known to be pregnant or breast-feeding, 11. Enrolled in a concomitant clinical trial of an investigational medicinal product, 12. White blood count < 2.5x109/l, 13. Haemoglobin < 4.0 mmol/l, 14. Thrombocytes < 50x109/l, 15. The use of strong CYP3A4 inducers, including the following drugs: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine, 1. Persisterende septische shock (>24 uur) met Mean Arterial Pressure (MAP) ≤ 65 mm Hg en serum lactaat > 4 mmol/L (36 mg/dL) ondanks adequate volume resuscitatie en vasopressie (noradrenaline > 0.2 μg/kg/min) voor > 6 uur, 2. Pre-existente chronische longziekte, inclusief: o Interstitiele longziekte o COPD Gold IV of FEV1<30% of predicted o DLCO <45% (indien bekend) o Total lung capacity (TLC) < 60% of predicted (indien bekend) 3. Chronische zuurstof therapie thuis 4. Pre-existent hartfalen met ventriculaire ejectie fractie <40%, 5. Active behandeling voor hematologische of niet-hematologische maligniteit met immuno- of chemotherapie, of thoracale radiotherapie in het laatste jaar, 6. Patiënt ondergaat extracorporeal life support (ECLS), 7. Ernstige chronische leverziekte (Child-Pugh score > 12), 8. Patiënten met een palliatief beleid, 9. Onvermogen van de IC staf om behandeling met de studiemedicatie binnen 48 uur na screening te starten 10. Patiënte is zwanger of geeft borstvoeding, 11. Patiënt is reeds in een andere medicijnenstudie geincludeerd, 12. Leukocyten < 2.5x109/l, 13. Hemoglobine < 4.0 mmol/l, 14. Trombocyten < 50x109/l, 15. Gebruik van sterke CYP3A4 inductoren, inclusief: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine,