The Effects of Oxiris on Systemic Inflammation and Endothelial dysFunction (EOSIEF)

August 31, 2020 updated by: St. Petersburg State Pavlov Medical University

The Effects of oXiris on Systemic Inflammation, Endothelial Dysfunction and Volume Control in Cardiac Surgery Patients Undergoing Cardiopulmonary Bypass.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Russian Federation
    • Russsia
      • Saint Petersburg, Russsia, Russian Federation, 197022
        • Recruiting
        • Pavlov First St. Petersburg State Medical University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Device: oXiris membrane
Open heart surgery patients in early postoperative period with clinical signs of fluid overload undergoing CRRT
No Intervention: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient volume status assessment in perioperative period
Time Frame: in 24 hours
To compare volume status in two arms based on CVP mmH2O and PAWP mmHg measurements
in 24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
survival after cardiac surgery
Time Frame: in 90 day
to compare in arms with oxiris treatment and standard protocol amount of survived patients
in 90 day
'ICU and hospital length of stay after cardiac surgery.
Time Frame: in 28 days
to compare in arms with oxiris treatment and standard protocol the amount of days spent in ICU wards and in hospital
in 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Petersburg State Pavlov Medical University

Investigators

  • Principal Investigator: Yury Polushin, PhD, Pavlov First St. Petersburg State Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 17, 2020

Primary Completion (Anticipated)

December 31, 2021

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

January 17, 2020

First Submitted That Met QC Criteria

February 4, 2020

First Posted (Actual)

February 5, 2020

Study Record Updates

Last Update Posted (Actual)

September 2, 2020

Last Update Submitted That Met QC Criteria

August 31, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1BAX-2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

de-identified individual participant data for all primary and secondary outcome measures will be made available

IPD Sharing Time Frame

data will be available within 1 year of study completion

IPD Sharing Access Criteria

data access request will be reviewed by an external independent review panel.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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