Clinical trial NCT03892174: Cytokine REmoval in CRitically Ill PAtients Requiring Surgical Therapy for Infective Endocarditis (RECReATE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endocarditis
Sepsis
Septic Shock
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2019-03-27
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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)

Primary outcomes:
measure: 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)
timeFrame: From baseline (pre-OR, t1) to day 1 post-OR (t3)
Secondary outcomes:
measure: Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or.
timeFrame: Baseline (pre-OP) to post-OR and 3 days post-Or
measure: Area under the curve of quantitative mHLA-DR expression
timeFrame: Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments).
measure: 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)
timeFrame: From baseline (pre-OR) to post-OR, and day 1 and 3 post-OR
measure: Change in organ dysfunction (Sepsis-related organ failure (SOFA) scores incl. subscores and Simplified acute physiology score (SAPS II scores) daily
timeFrame: 7-day timeframe (starting from ICu admission, assessed at day 90)
measure: Length of ICU and hospital stay (days after surgical intervention).
timeFrame: Number of days on ICU and in hospital (assessed at day 90)
measure: Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge
timeFrame: Total number of TISS points on ICU (cumulative), assessed at day 90
measure: Total amount of infused volume/transfusions on ICU
timeFrame: 90 days
measure: Duration of vasoactive drug therapy
timeFrame: 90 days
measure: Duration of invasive mechanical ventilation
timeFrame: 90 days
measure: ICU mortality rate
timeFrame: ICU stay (assessed at day 90)
measure: Hospital mortality rate
timeFrame: hospital stay (assessed at day 90)
measure: 28 day mortality rate
timeFrame: 28 days beginning from ICU admission (assessed at day 90)
measure: 90 day mortality rate
timeFrame: 90 days beginning from ICU admission (assessed at day 90)
measure: Duration of renal replacement therapy
timeFrame: 90 days
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Dept of Intensive Care Medicine
Study officials:
affiliation: Inselspital, Bern University Hospital
name: Lars Englberger, MD
role: STUDY_DIRECTOR
References:
citation: 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.0000000000019580.