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

Overview

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)

Interventions

• Biological ARTICE
  Extracorporal treatment with purified granulocyte concentrate

Primary outcome measures

• Safety and tolerability of the ARTICE therapy, composed of new onset of serious adverse events from re-evaluation on Day 2 through Day 28 [Time frame: From re-evaluation on Day 2 through Day 28]

Secondary outcome measures (12)

• All cause mortality through Day 28 [Time frame: From re-evaluation on Day 2 through Day 28]
• All cause mortality through Day 90 [Time frame: From re-evaluation on Day 2 through Day 90]
• All-cause in-hospital mortality [Time frame: From re-evaluation on Day 2 through until hospital discharge]
• Daily changes in total SOFA and SOFA sub-scores [Time frame: Until Day 10]
• Time course of key inflammatory/ immunological markers in between the two groups. [Time frame: From re-evaluation on Day 2 until Day 28]
• Time to complete organ failure resolution [Time frame: From re-evaluation on Day 2 until Day 28 with special focus on D14 an D21]
• ICU length of stay Measured / Confirmed on day 28 retrospectively. Units: Days [Time frame: Until Day 28]
• Number of hospital-free days. Measured / Confirmed on day 28 retrospectively. Units: Days [Time frame: Until Day 28]
• Number of ICU-free days Measured / Confirmed on day 28 retrospectively. Units: Days [Time frame: Until day 28]
• Number of vasopressor- free days [Time frame: From re-evaluation on Day 2 until Day 28]
• Number of mechanical-ventilator-free days [Time frame: From re-evaluation on Day 2 until Day 28]
• Number of renal-replacement-free days [Time frame: From re-evaluation on Day 2 until Day 28]

Eligibility criteria

Inclusion criteria

• Adult subjects

• ≥ 18 years of age
• 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
• Subjects ≥ 80 years of age shall have a Clinical Frailty Scale of <5 to be enrolled.
• 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.
• Blood lactate >2 mmol/L despite adequate volume resuscitation during the current sepsis episode
• Source control achieved / in progress in the judgement of the investigator
• 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.
• Subjects must have received adequate volume replacement in the judgement of the investigator.
• 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

• Acute or chronic leukemia,
• Bilirubin ≥ 2 mg/dL (≥33 µmol/L),
• Ongoing (concomitant) or prior within the last 6 month any chemotherapy or radiotherapy for malignancy,
• Autoimmune disease with systemic medication of ≥10 mg prednisolone equivalent,
• Previous transplantation,
• Subjects receiving interferon therapy (14 days prior randomisation),
• Acute pulmonary embolism within the last 72 hours,
• Ischemic stroke or intracranial bleeding within the last 3 months
• Suspicion of concomitant acute coronary syndrome based on clinical symptoms and/or ECG within the last 72 hours,
• Cardiopulmonary resuscitation within last 7 days,
• Moribund subject (life expectancy <72 hours), in the judgement of the investigator
• Presence of a do-not-resuscitate or do-not-intubate order,
• Known HIV infection or chronic viral hepatitis,
• Isolated Urosepsis,
• Pregnancy/nursing period,
• Primary cause of hypotension not due to sepsis (e.g. major trauma including traumatic brain injury, haemorrhage, burns, or congestive heart failure/cardiogenic shock),
• Previous sepsis with ICU admission within this hospital stay,
• Known/suspected acute mesenteric ischaemia,
• 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,
• Decision to limit full care taken before obtaining informed consent,
• Prior enrolment in the trial,
• 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,
• multiple injuries including polytrauma and burn >20% TBSA (2° or 3°),
• Diagnosed and documented pre-existing dementia,
• Severe Covid-Pneumonia

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 20 centers

• Universitätsklinikum Freiburg, Interdisziplinäre Medizinische Intensivtherapie (IMIT) — Freiburg im Breisgau
• Universitätsklinikum Regensburg, Klinik für Anästhesiologie — Regensburg
• Universitätsklinikum Bonn, Klinik und Poliklinik für Anästhesiologie und Operative Intensi — Bonn
• Universitätsklinikum Köln, Klinik für Anästhesiologie und Operative Intensivmedizin — Cologne
• Helios Klinikum Aue — Aue
• Universitätsklinikum Leipzig, Klinik und PK für Anästhesiologie und Intensivtherapie — Leipzig
• Universitätsklinikum Halle (Saale), Universitätsklinik für Anästhesiologie und Operative I — Halle
• UNIVERSITÄTSKLINIKUM Schleswig-Holstein Campus Kiel — Kiel
• … and 12 more centers

Identifiers

NCT: NCT05442710 · ReActIF-ICE_ZKSJ0124

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗