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

Обзор

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)

Вмешательства

• Биопрепарат ARTICE
  Extracorporal treatment with purified granulocyte concentrate

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 20 центров

• 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
• … и ещё 12 центров

Идентификаторы

NCT: NCT05442710 · ReActIF-ICE_ZKSJ0124

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗