Recovery From Acute Immune Failure in Septic Shock by Immune Cell Extracorporeal Therapy

Inclusion Criteria:

1. Adult subjects

2. ≥ 18 years of age

3. with septic shock, defined as those with septic shock according to"Sepsis-3-Definition" who additionally require norepinephrine at a dose of ≥ 0.15 mcg/kg/min (and/or vasopressin at any dose) for a minimum of 6 hours (within the last 48 hours), to maintain a MAP ≥65 mmHg

4. Subjects ≥ 80 years of age shall have a Clinical Frailty Scale of <5 to beenrolled.

5. Fulfillment of the definition of septic shock, not longer than 48h beforerandomization. I.e. the 48h start at the end of the 6h period.

6. Blood lactate >2 mmol/L despite adequate volume resuscitation during the currentsepsis episode

7. Source control achieved / in progress in the judgement of the investigator

8. Subjects are required to have central venous access and an arterial line, and theseare expected to remain present for at least the initial 48 hours of study.

9. Subjects must have received adequate volume replacement in the judgement of theinvestigator.

10. Subject or legal surrogate is willing and able to provide written informed consentand comply with all protocol requirements or confirmation of the urgency ofparticipation in the clinical trial and the possible benefit to the subject by anindependent consultant or the implementation of other established proceduresaccording to the local regulations of the contributing centre to include subjectswho are unable to provide informed consent.

Exclusion Criteria:

1. Acute or chronic leukemia,

2. Bilirubin ≥ 2 mg/dL (≥33 µmol/L),

3. Ongoing (concomitant) or prior within the last 6 month any chemotherapy orradiotherapy for malignancy,

4. Autoimmune disease with systemic medication of ≥10 mg prednisolone equivalent,

5. Previous transplantation,

6. Subjects receiving interferon therapy (14 days prior randomisation),

7. Acute pulmonary embolism within the last 72 hours,

8. Ischemic stroke or intracranial bleeding within the last 3 months

9. Suspicion of concomitant acute coronary syndrome based on clinical symptoms and/orECG within the last 72 hours,

10. Cardiopulmonary resuscitation within last 7 days,

11. Moribund subject (life expectancy <72 hours), in the judgement of the investigator

12. Presence of a do-not-resuscitate or do-not-intubate order,

13. Known HIV infection or chronic viral hepatitis,

14. Isolated Urosepsis,

15. Pregnancy/nursing period,

16. Primary cause of hypotension not due to sepsis (e.g. major trauma includingtraumatic brain injury, haemorrhage, burns, or congestive heart failure/cardiogenicshock),

17. Previous sepsis with ICU admission within this hospital stay,

18. Known/suspected acute mesenteric ischaemia,

19. Chronic mechanical ventilation for any reason OR severe COPD requiring eithercontinuous daily oxygen use during the preceding 30 days or mechanical ventilation (for acute exacerbation of COPD) during the preceding 30 days,

20. Decision to limit full care taken before obtaining informed consent,

21. Prior enrolment in the trial,

22. Prior use of an investigational medicinal product within the last month OR plannedor concurrent participation in a clinical trial for any investigational drug ordevice,

23. multiple injuries including polytrauma and burn >20% TBSA (2° or 3°),

24. Diagnosed and documented pre-existing dementia,

25. Severe Covid-Pneumonia