Cytokine REmoval in CRitically Ill PAtients Requiring Surgical Therapy for Infective Endocarditis (RECReATE)

Официальное название

Cytokine REmoval in CRitically Ill PAtients Requiring Surgical Therapy for Infective Endocarditis (RECReATE) - an Investigator-initiated Prospective Randomized Controlled Clinical Trial Comparing Two Established Clinical Protocols

Обзор

Infectious endocarditis (IE) and other severe infections are well-known to induce significant changes in the immune response including immune functionality in a considerable number of affected patients. In fact, numerous patients with IE develop a persistent functional immunological phenotype that can best be characterized by a profound anti-inflammation and/or functional anergy. This was previously referred to as "injury-associated immunosuppression (IAI)" by Pfortmüller et al., published in Intensive Care Medicine Experimental 2017. IAI can be assessed by measurement of cellular (functional) markers. Persistence of IAI is associated with prolonged ICU length of stay, increased secondary infection rates, and death. Immunomodulation to reverse IAI was shown beneficial in immunostimulatory (randomized controlled) clinical trials. CytoSorb® treatment is currently used as standard of care in some institutions in surgically treated IE patients. The investigators aim to investigate two accepted treatment protocols and aim to explore whether adsorption with a cytokine adsorption filter can increase immune competence in treated individuals.

Вмешательства

• Другое Treatment protocol with adsorption
  Adsorption while patients are in the OR on the extracorporeal circuit

Первичные конечные точки

• Change in quantitative expression of monocytic Human Leukocyte Antigen (mHLA)-DR expression (Antibodies per cell on Cluster of Differentiation (CD)14+ monocytes/macrophages, assessed using a quantitative standardized assay) [Срок оценки: From baseline (pre-OR, t1) to day 1 post-OR (t3)]

Вторичные конечные точки (12)

• Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or. [Срок оценки: Baseline (pre-OP) to post-OR and 3 days post-Or]
• Area under the curve of quantitative mHLA-DR expression [Срок оценки: Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments).]
• Change in inflammatory markers including cytokines (Interleukin (IL)-6, IL-10, C-reactive protein, White blood cell count, multiplex Enzyme linked immunosorbent assay, and inflammatory prohormones) [Срок оценки: From baseline (pre-OR) to post-OR, and day 1 and 3 post-OR]
• Change in organ dysfunction (Sepsis-related organ failure (SOFA) scores incl. subscores and Simplified acute physiology score (SAPS II scores) daily [Срок оценки: 7-day timeframe (starting from ICu admission, assessed at day 90)]
• Length of ICU and hospital stay (days after surgical intervention). [Срок оценки: Number of days on ICU and in hospital (assessed at day 90)]
• Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge [Срок оценки: Total number of TISS points on ICU (cumulative), assessed at day 90]
• Total amount of infused volume/transfusions on ICU [Срок оценки: 90 days]
• Duration of vasoactive drug therapy [Срок оценки: 90 days]
• Duration of invasive mechanical ventilation [Срок оценки: 90 days]
• ICU mortality rate [Срок оценки: ICU stay (assessed at day 90)]
• Hospital mortality rate [Срок оценки: hospital stay (assessed at day 90)]
• 28 day mortality rate [Срок оценки: 28 days beginning from ICU admission (assessed at day 90)]

Критерии участия

Критерии включения

• Subjects scheduled for routine cardiac surgery for infectious endocarditis (diagnosed according to the predefined "DUKE" criteria) with antibiotic therapy for ≤ 14 days.
• Presence of informed consent
• Age ≥18 yrs.

Критерии исключения

• Previous treatment (last 6 months) with immunologically-active biologicals or specific immunomodulatory drugs (e.g. Rituximab)
• high-dose chronic (i.e. before onset of infectious endocarditis) steroid medication with prednisone equivalent of >30 mg/d
• Patients on Extracorporeal membrane oxygenation (ECMO), or any other (pre-operative) cardiac assist device
• Moribund patient (life expectancy <14 days)

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

Швейцария · 1 центр

• Dept of Intensive Care Medicine — Bern

Публикации

• Gisler F, Spinetti T, Erdoes G, Luedi MM, Pfortmueller CA, Messmer AS, Jenni H, Englberger L, Schefold JC. Cytokine Removal in Critically Ill Patients Requiring Surgical Therapy for Infective Endocarditis (RECReATE): An Investigator-initiated Prospective Randomized Controlled Clinical Trial Comparing Two Established Clinical Protocols. Medicine (Baltimore). 2020 Apr;99(15):e19580. doi: 10.1097/MD. PMID 32282706

Идентификаторы

NCT: NCT03892174 · RECREATE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗