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The Effects of Oxiris on Systemic Inflammation and Endothelial dysFunction

Not Applicable
Conditions
Acute Kidney Injury Due to Circulatory Failure (Disorder)
Interventions
Device: oXiris membrane
Registration Number
NCT04257006
Lead Sponsor
St. Petersburg State Pavlov Medical University
Brief Summary

CS-AKI occurring in 20% to 70% of cases depending of the type of cardiac surgery. The systemic inflammatory response is often observed and associated with increased risk of AKI. Cardiopulmonary bypass (CPB) induces a complex inflammatory response that has a multifactorial pathogenesis. The inflammatory response is triggered by exposure of the blood to artificial surfaces during extracorporeal circulation, ischemia/reperfusion injuries, translocation of gram-negative bacteria from the intestinal tract, small amounts of LPS in IV solutions. SIRS during CPB with high levels of inflammatory mediators, active complement proteins and LPS provoke endothelial dysfunction- retraction of endothelial cells with increasing vascular permeability and thrombogenic activity, also inflammatory mediators activate leukocytes and they enhance vascular permeability by affecting endothelial cells and vascular basement membrane. The systemic inflammation and endothelial dysfunction are the basis for multiple organ dysfunction syndrome. Vascular integrity damage during cardiac surgery entail redistribution of fluids with interstitial fluid accumulation and require accurate volume control (pertinent removal of "CPB priming volume"), especially in patients with CKD (low GFR) with high risks of AKI.

Detailed Description

Specific details of Treatment/Intervention: (prescription and/or therapy, devices, equipment, solutions, product to be used in conducting study:

To apply Prismaflex system with oXiris membrane after cardiopulmonary bypass in SCUF modality for CPB priming volume elimination.

Duration of procedure: 6 hours Blood flow:150-200 ml/min Anticoagulation: no additional heparinization.

According to the features of oXiris membrane:

1. Cytokines, complement, endotoxin adsorptive capacity.

2. Capability of accurate fluid balance management after cardiac surgery and CPB.

3. Reduced demand of anticoagulation therapy for CRRT in patients with high risk of bleeding.

The goal of the research:

1. To evaluate effect of adsorption of oXiris membrane on levels of complement (C3a, C5a), pro- and anti-inflammatory cytokines (IL-1β, TNF-α,IL-6,Il-8, IL-10,TGF-β), LPS (EAA levels) after CPB.

2. To evaluate leukocytes activation after CPB and after inflammatory mediators adsorption with oXiris (CD11b/CD18)

3. To evaluate endothelial dysfunction after CPB and after CRRT with oXiris: endothelial/leukocytes interactions (ICAM-1, VCAM-1), biomarkers of endothelial permeability (angiopoetin-2, sFLT-1), biomarkers of endothelial coagulopathy (von Willebrand factor, thrombomodulin)

4. To evaluate effect of volume control with CRRT on CS-AKI and dependence on mechanical ventilation after cardiac surgery, regarding volume overload in patients undergoing CPB with "priming volume" infusion.

5. To evaluate stage and topography of cardiac surgery associated acute kidney injury (creatinine, cystatin C, NGAL, KIM-1, β2-microglobuline) in patients in two arms: oXiris and standard protocol.

6. To evaluate adsorptive and volume control feasible effects of oXiris membrane on volume management (CVP,PAWP), LPS adsorption, reduction of systemic inflammation , endothelium dysfunction and AKI after cardiac surgery with CPB in comparison with standard protocol.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
Inclusion Criteria
  • elective cardiac surgery patients undergoing CPB (>60 minutes) with valve replacement and CABG.
Exclusion Criteria
  • Immunosuppressive therapy, CKD 4 and 5 stages, RRT in last 90 days, pregnancy, autoimmune disease, allergy to heparin.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
patients undergoing CRRT with oXiris membraneoXiris membraneElective cardiac surgery patients undergoing CPB we will range in 2 groups: I- with Prismaflex set oXiris (SCUF) after CPB, II- standard protocol. Indications for CRRT (SCUF) with oXiris after ICU admission: 1. Signs of pulmonary edema after cardiac surgery, verified with X-ray control. Or high risk of pulmonary edema after cardiac surgery: 1. Fluid overload ≥ 10%, measured with equation (%fluid overload= ((total fluid in- total fluid out)/admission body weight\*100) 2. CVP (central venous pressure) ˃ 12 mm H2O. 3. PAWP (pulmonary arterial wedge pressure) ˃ 12 mm Hg, measured by Swan-Ganz catheter. In this arm the treatment of fluid overload will be provided via SCUF with oxiris membrane
Primary Outcome Measures
NameTimeMethod
Patient volume status assessment in perioperative periodin 24 hours

To compare volume status in two arms based on CVP mmH2O and PAWP mmHg measurements

Secondary Outcome Measures
NameTimeMethod
survival after cardiac surgeryin 90 day

to compare in arms with oxiris treatment and standard protocol amount of survived patients

'ICU and hospital length of stay after cardiac surgery.in 28 days

to compare in arms with oxiris treatment and standard protocol the amount of days spent in ICU wards and in hospital

Trial Locations

Locations (1)

Pavlov First St. Petersburg State Medical University

🇷🇺

Saint Petersburg, Russsia, Russian Federation

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