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Recruiting NCT03892174

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

No phase Interventional Endocarditis Sepsis Septic Shock

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Treatment protocol with adsorption.
Who it may be relevant to
Registry conditions: Endocarditis, Sepsis, Septic Shock. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Switzerland
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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

Overview

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.

Interventions

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

Primary outcome measures

  • 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) [Time frame: From baseline (pre-OR, t1) to day 1 post-OR (t3)]
Secondary outcome measures (12)
  • Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or. [Time frame: Baseline (pre-OP) to post-OR and 3 days post-Or]
  • Area under the curve of quantitative mHLA-DR expression [Time frame: 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) [Time frame: 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 [Time frame: 7-day timeframe (starting from ICu admission, assessed at day 90)]
  • Length of ICU and hospital stay (days after surgical intervention). [Time frame: Number of days on ICU and in hospital (assessed at day 90)]
  • Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge [Time frame: Total number of TISS points on ICU (cumulative), assessed at day 90]
  • Total amount of infused volume/transfusions on ICU [Time frame: 90 days]
  • Duration of vasoactive drug therapy [Time frame: 90 days]
  • Duration of invasive mechanical ventilation [Time frame: 90 days]
  • ICU mortality rate [Time frame: ICU stay (assessed at day 90)]
  • Hospital mortality rate [Time frame: hospital stay (assessed at day 90)]
  • 28 day mortality rate [Time frame: 28 days beginning from ICU admission (assessed at day 90)]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Switzerland · 1 center
  • Dept of Intensive Care Medicine — Bern

Publications

  • 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

Identifiers

NCT: NCT03892174 · RECREATE

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗