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

Sepsis Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03892174
• Other study ID #: RECREATE
• Status: Recruiting
• Phase: N/A
• Start date: November 14, 2019
• Est. completion date: December 1, 2024

Study information

• Verified date: January 2023
• Source: University Hospital Inselspital, Berne
• Contact: Joerg C Schefold, MD
• Phone: 0041-31-632
• Email: joerg.schefold[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 1, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Endocarditis
• Endocarditis, Bacterial
• Sepsis
• Septic Shock

Intervention

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

Locations

Country	Name	City	State
Switzerland	Dept of Intensive Care Medicine	Bern

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		From baseline (pre-OR, t1) to day 1 post-OR (t3)
Secondary	Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or.	Course of mHLA-DR	Baseline (pre-OP) to post-OR and 3 days post-Or
Secondary	Area under the curve of quantitative mHLA-DR expression	Area under the curves mHLA-DR	Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments).
Secondary	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)	Change in inflammatory parameters	From baseline (pre-OR) to post-OR, and day 1 and 3 post-OR
Secondary	Change in organ dysfunction (Sepsis-related organ failure (SOFA) scores incl. subscores and Simplified acute physiology score (SAPS II scores) daily	Course of organ dysfunction	7-day timeframe (starting from ICu admission, assessed at day 90)
Secondary	Length of ICU and hospital stay (days after surgical intervention).	Length of stay	Number of days on ICU and in hospital (assessed at day 90)
Secondary	Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge	Resource use	Total number of TISS points on ICU (cumulative), assessed at day 90
Secondary	Total amount of infused volume/transfusions on ICU	Need for fluid therapy	90 days
Secondary	Duration of vasoactive drug therapy	Vasopressor use	90 days
Secondary	Duration of invasive mechanical ventilation	Use of organ support therapy (number of days on mechanical ventilation)	90 days
Secondary	ICU mortality rate	Number of non-surviving patients in both study groups	ICU stay (assessed at day 90)
Secondary	Hospital mortality rate	Number of non-surviving patients in both study groups	hospital stay (assessed at day 90)
Secondary	28 day mortality rate	Number of non-surviving patients in both study groups	28 days beginning from ICU admission (assessed at day 90)
Secondary	90 day mortality rate	Number of non-surviving patients in both study groups	90 days beginning from ICU admission (assessed at day 90)
Secondary	Duration of renal replacement therapy	Use of organ support therapy (number of days on renal replacement therapy)	90 days