Clinical trial NCT05442710: Recovery From Acute Immune Failure in Septic Shock by Immune Cell Extracorporeal Therapy
Official title: Recovery From Acute Immune Failure in Septic Shock by Immune Cell Extracorporeal Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sepsis, Severe
Lead sponsor: Artcline GmbH
Sponsor class: INDUSTRY
Collaborators: name: Zentrum für Klinische Studien Jena
name: RQMplus
First posted: 2022-07-05
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, randomized, controlled parallel-group study
Primary purpose: TREATMENT

Brief summary: Evaluation of a novel therapy approach for severe sepsis patients. Subjects randomized into the treatment arm receive treatment with an immune cell perfusion system on top of standard care.

This may contribute to the improvement of the impaired organ function of septic shock patients by assisting the impaired immune system (immune competence enhancement = ARTICE)


Eligibility criteria: Inclusion Criteria:

1. Adult subjects

   1. ≥ 18 years of age
   2. 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
   3. Subjects ≥ 80 years of age shall have a Clinical Frailty Scale of \<5 to be enrolled.
2. Fulfillment of the definition of 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 during the current sepsis episode
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 adequate 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. Bilirubin ≥ 2 mg/dL (≥33 µmol/L),
3. Ongoing (concomitant) or prior within the last 6 month any chemotherapy or radiotherapy 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/or ECG 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 including traumatic brain injury, haemorrhage, burns, or congestive heart failure/cardiogenic shock),
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 either continuous 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 planned or concurrent participation in a clinical trial for any investigational drug or device,
23. multiple injuries including polytrauma and burn \>20% TBSA (2° or 3°),
24. Diagnosed and documented pre-existing dementia,
25. Severe Covid-Pneumonia

Primary outcomes:
measure: Safety and tolerability of the ARTICE therapy, composed of new onset of serious adverse events from re-evaluation on Day 2 through Day 28
timeFrame: From re-evaluation on Day 2 through Day 28
Secondary outcomes:
measure: All cause mortality through Day 28
timeFrame: From re-evaluation on Day 2 through Day 28
measure: All cause mortality through Day 90
timeFrame: From re-evaluation on Day 2 through Day 90
measure: All-cause in-hospital mortality
timeFrame: From re-evaluation on Day 2 through until hospital discharge
measure: Daily changes in total SOFA and SOFA sub-scores
timeFrame: Until Day 10
measure: Time course of key inflammatory/ immunological markers in between the two groups.
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Time to complete organ failure resolution
timeFrame: From re-evaluation on Day 2 until Day 28 with special focus on D14 an D21
measure: ICU length of stay Measured / Confirmed on day 28 retrospectively. Units: Days
timeFrame: Until Day 28
measure: Number of hospital-free days. Measured / Confirmed on day 28 retrospectively. Units: Days
timeFrame: Until Day 28
measure: Number of ICU-free days Measured / Confirmed on day 28 retrospectively. Units: Days
timeFrame: Until day 28
measure: Number of vasopressor- free days
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Number of mechanical-ventilator-free days
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Number of renal-replacement-free days
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Number of days without antimicrobial therapy
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Frequency of secondary infections
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Antibiotic exposure days until hospital discharge
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Days [n] alive without antibiotics until hospital discharge
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Total daily dose of noradrenalin (NA) administered on each day
timeFrame: From re-evaluation on Day 2 until Day 10
measure: Maximum daily dose of noradrenalin administration on treatment days
timeFrame: From re-evaluation on Day 2 until Day 10
measure: Occurrence of virus induced inflammation episodes
timeFrame: From re-evaluation on Day 2 until Day 28
measure: Quality of life assessment
timeFrame: Until day 90
measure: Occurrence of cognitive decline
timeFrame: Until day 90
measure: Time course of key biomarkers of neuroaxonal injury
timeFrame: Until day 28
measure: Inflammatory mRNA profiling analysis
timeFrame: until day 10
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Interdisziplinäre Medizinische Intensivtherapie (IMIT)
state: Baden-Württemberg
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik für Anästhesiologie
state: Bayern
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Universitätsklinikum Köln, Klinik für Anästhesiologie und Operative Intensivmedizin
state: Nordrhein-Westfalen
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Saale), Universitätsklinik für Anästhesiologie und Operative Intensivmedizin
state: Sachsen-Anhalt
city: Aue
country: Germany
facility: Helios Klinikum Aue
state: Sachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik und PK für Anästhesiologie und Intensivtherapie
state: Sachsen
city: Kiel
country: Germany
facility: UNIVERSITÄTSKLINIKUM Schleswig-Holstein Campus Kiel
state: Schleswig Holstein
city: Berlin
country: Germany
facility: Charité Berlin, Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin
city: Braunschweig
country: Germany
facility: Klinikum Braunschweig, Medizinische Klinik V
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Nephrologie
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy
city: Hildesheim
country: Germany
facility: Helios Klinikum HIldesheim
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg, Klinik für Intensiv- und Rettungsmedizin
city: Mainz
country: Germany
facility: University Medical Center Mainz, Study center for Anesthesiology
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: Minden
country: Germany
facility: University Hospital Minden, Departmenr of Anaesthesiology, intensive and emergency care
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg, Universitätsklinik für Anästhesiologie/ Intensivmedizin
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Abteilung KAI
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin, Department for intensive care
Study officials:
affiliation: University Hospital Rostock
name: Daniel Reuter, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References: