The Effects of Oxiris on Systemic Inflammation and Endothelial dysFunction

NCT ID: NCT04257006

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-17
• Study Completion Date: 2022-06-01

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.

Conditions

Acute Kidney Injury Due to Circulatory Failure (Disorder)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

patients undergoing CRRT with oXiris membrane

Elective 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

Group Type: EXPERIMENTAL

oXiris membrane

Intervention Type: DEVICE

Open heart surgery patients in early postoperative period with clinical signs of fluid overload undergoing CRRT

standard protocol

Elective 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 management of fluid overload will be provided via diuretics or IHD (in condition diuretics treatment resistance)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

oXiris membrane

Open heart surgery patients in early postoperative period with clinical signs of fluid overload undergoing CRRT

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yury Polushin, PhD

Role: PRINCIPAL_INVESTIGATOR

Pavlov First St. Petersburg State Medical University

Locations

Pavlov First St. Petersburg State Medical University

Saint Petersburg, Russsia, Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Yury Polushin, PhD

Role: CONTACT

polushin1@gmail.com

+7 (812) 338-66-49

Dmitry Sokolov, MD

Role: CONTACT

sokolovdv82@gmail.com

+7(911)7193333

Facility Contacts

Yury Polushin, PhD

Role: primary

polushin1@gmail.com

+78123387823

Dmitry Sokolov, MD

Role: backup

sokolovdv82@gmail.com

+79117193333

Other Identifiers

1BAX-2020

Identifier Type: -

Identifier Source: org_study_id