Recovery From Acute Immune Failure in Septic Shock by Immune Cell Extracorporeal Therapy (ReActiF-ICE)

This is an interventional treatment trial for Sepsis, Severe Read More

Inclusion Criteria:

1. Adult subjects≥ 18 years and ≤ 80 years of age with refractory septic shock, defined as those with septic shock according to" Sepsis-3-Definition" who additionally require a norepinephrine dose of ≥ 0.2 mcg/kg/min (and/or vasopressin at any dose) for a minimum of 6 hours (within the last 48 hours), to maintain a MAP between 55-70 mmHg.
2. Fullfillment of the definition of refractory septic shock, not longer than 48h before randomization, i.E. the 48h start at the end of the 6h period
3. Blood lactate >2 mmol/L despite adequate volume resuscitation, at least once at the onset of septic shock.
4. Source control achieved / in progress in the judgement of the investigator
5. Subjects are required to have central venous access and an arterial line, and these are expected to remain present for at least the initial 48 hours of study.
6. Subjects must have received adequately volume replacement in the judgement of the investigator.
7. Subject or legal surrogate is willing and able to provide written informed consent and comply with all protocol requirements or confirmation of the urgency of participation in the clinical trial and the possible benefit to the subject by an independent consultant or the implementation of other established procedures according to the local regulations of the contributing centre to include subjects who are unable to provide informed consent.

Exclusion Criteria:

1. Acute or chronic leukemia,
2. Severe thrombocytopenia (<50,000/µl),
3. Bilirubin ≥ 2 mg/dL (≥33 µmol/L)
4. Ferritin > 2.000 ng/mL
5. Ongoing (concomitant) or prior within the last 6 months chemotherapy or radiotherapy for malignancy,
6. Autoimmune disease with systemic medication of ≥10 mg prednisolone equivalent,
7. Previous transplantation,
8. Subjects receiving interferon therapy ( 14 days prior to randomization),
9. Acute pulmonary embolism or acute myocardial infarction within last 72 hours,
10. Stroke or intracranial bleeding within the last 3 months
11. Suspicion of concomitant acute coronary syndrome based on clinical symptoms and/or ECG during this episode of septic shock.
12. Cardiopulmonary resuscitation within last 7 days,
13. Moribund subject (life expectancy <72 hours in the judgement of the investigator),
14. Presence of a do-not-resuscitate or do-not-intubate order,
15. Known HIV infection or chronic viral hepatitis.
16. Urosepsis,
17. Pregnancy/nursing period,
18. ARTICE treatment presumably not possible on day 2 after randomization (due to donor availability on weekends/public holidays).
19. Primary cause of hypotension not due to sepsis (e.g. major trauma including traumatic brain injury, haemorrhage, burns, or congestive heart failure/cardiogenic shock).
20. Previous sepsis with ICU admission within this hospital stay.
21. Known/suspected acute mesenteric ischaemia.
22. Chronic mechanical ventilation for any reason OR severe COPD requiring either continuous daily oxygen use during the preceding 30 days or mechanical ventilation (for acute exacerbation of COPD) during the preceding 30 days.
23. Decision to limit full care taken before obtaining informed consent.
24. Prior enrolment in the trial.
25. Prior use of an investigational medicinal product within the last month OR planned or concurrent participation in a clinical trial for any investigational drug or device
26. known planned surgery in the next 48 hrs after randomization (e.g. "second look surgery")
27. multiple injuries including polytrauma and burn >20% TBSA (2° or 3°)
28. Proven or suspected pre-existing dementia
29. Acute COVID-19 infection.