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

NCT03892174 | Recruiting

• 1 other identifier: RECREATE
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Endocarditis; Sepsis; Septic Shock

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or.

  Baseline (pre-OP) to post-OR and 3 days post-Or

• Area under the curve of quantitative mHLA-DR expression

  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)

  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

  7-day timeframe (starting from ICu admission, assessed at day 90)

• Length of ICU and hospital stay (days after surgical intervention).

  Number of days on ICU and in hospital (assessed at day 90)

Study Arms (2)

Treatment protocol without adsorption

NO INTERVENTION

Treatment protocol with adsorption

ACTIVE COMPARATOR

Other: Treatment protocol with adsorption

Interventions

Treatment protocol with adsorption OTHER

Adsorption while patients are in the OR on the extracorporeal circuit

Treatment protocol with adsorption

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Dept of Intensive Care Medicine

Bern, 3010, Switzerland

RECRUITING

Related Publications (1)

• 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.

  PMID: 32282706 DERIVED

MeSH Terms

Conditions

Endocarditis; Sepsis; Shock, Septic

Interventions

Clinical Protocols; Adsorption

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Physical Phenomena; Chemical Phenomena

Study Officials

• Lars Englberger, MD

  Inselspital, Bern University Hospital

  STUDY DIRECTOR

Central Study Contacts

Joerg C Schefold, MD

CONTACT

0041-31-632; joerg.schefold@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: March 27, 2019
• Study Start: November 14, 2019
• Primary Completion: November 7, 2024
• Study Completion: December 31, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)