Endocarditis, Sepsis, Septic Shock
Conditions
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.
Interventions
OTHERTreatment protocol with adsorption
Adsorption while patients are in the OR on the extracorporeal circuit
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Course of mHLA-DR |
| Area under the curve of quantitative mHLA-DR expression | Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments). | Area under the curves mHLA-DR |
| Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge | Total number of TISS points on ICU (cumulative), assessed at day 90 | Resource use |
| 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 inflammatory parameters |
| 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) | Course of organ dysfunction |
| Length of ICU and hospital stay (days after surgical intervention). | Number of days on ICU and in hospital (assessed at day 90) | Length of stay |
| Hospital mortality rate | hospital stay (assessed at day 90) | Number of non-surviving patients in both study groups |
| Duration of vasoactive drug therapy | 90 days | Vasopressor use |
| Duration of invasive mechanical ventilation | 90 days | Use of organ support therapy (number of days on mechanical ventilation) |
| ICU mortality rate | ICU stay (assessed at day 90) | Number of non-surviving patients in both study groups |
| 28 day mortality rate | 28 days beginning from ICU admission (assessed at day 90) | Number of non-surviving patients in both study groups |
| 90 day mortality rate | 90 days beginning from ICU admission (assessed at day 90) | Number of non-surviving patients in both study groups |
| Duration of renal replacement therapy | 90 days | Use of organ support therapy (number of days on renal replacement therapy) |
| Total amount of infused volume/transfusions on ICU | 90 days | Need for fluid therapy |
Countries
Switzerland
Contacts
Primary ContactJoerg C Schefold, MD
Outcome results
None listed