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Extracorporeal Cytokine Adsorption in Cardiac Surgery (IMEECCACS)

U

University Medical Centre Ljubljana

Status and phase

Completed
Phase 3

Conditions

Cardiopulmonary Bypass

Treatments

Drug: Methylprednisolone
Device: CytoSorb

Study type

Interventional

Funder types

Other

Identifiers

NCT02666703
ARRS-RPROJ-2014-191

Details and patient eligibility

About

The modern era of cardiac surgery began in early 1950s with the introduction of cardiopulmonary bypass (CPB). Although it has been clearly shown that CPB is almost unavoidable for most open heart operations, an undesirable systemic inflammatory response syndrome (SIRS) is associated with its use. This complex chain of events has strong similarities with sepsis and may contribute to the development of postoperative complications and multiple organ failure (MOF). It has been shown that an excessive compensatory anti-inflammatory response (CARS) after SIRS can lead to immune paralysis and increased rate of hospital acquired infection. The balance of pro-inflammatory and anti-inflammatory mediators determines the inflammatory response and the clinical outcome. Accordingly, great efforts have been focused on therapeutic interventions aimed at reducing the inflammatory reactions during CPB, including pharmacologic strategies and modification of surgical techniques or mechanical devices. Such therapies may provide improvements in patient outcome after open heart operations. Among pharmacologic strategies is the prophylaxis with corticosteroids, which have been used during open heart surgery for more than 30 years. Many studies, both experimental and clinical, failed to produce evidence in favor of steroid treatment. As far as medical devices are concerned, the use of extracorporeal cytokine filter CytoSorb looks promising in cardiac surgery. It was recently approved by European Medicines Agency as an active treatment to fight cytokine storm.

Serum paraoxonase 1 (PON1) is a lipo-lactonase, being associated with HDL that has an anti-inflammatory role and protects against atherosclerosis. Low levels of PON1 are associated with venous graft occlusion in patients with coronary artery bypass grafting. PON1 reduces monocyte chemotaxis and adhesion to endothelial cells, leading to inhibition of the differentiation of monocytes into macrophages. The effects of cytokine adsorption therapy on PON1 are unknown.

The aim of the study is to explore the effects of extracorporeal immunoadsorption during CPB on pro-inflammatory and anti-inflammatory protective mediators and cellular immune status in cardiac surgery.

Full description

Patients undergoing complex cardiac surgery with CPB (eg: combined valve and coronary bypass grafting surgery, concomitant valve surgery, surgery of the ascending aorta and aortic arch, as well as re-operations of the same type) will be enrolled in the study after giving the signed informed consent. They will be randomized into 3 groups: 1. study (CytoSorb) group, 2. control group, and 3. corticosteroid group. Immune response [TNF-alfa (tumor necrosis factor-alpha), IL(interleukin)-1, IL-6, IL-8, IL-10, complement C5a, lymphocyte cellular markers (CD64, CD163), miRNA (micro RNA), PON1 activity, as well as lipid status, hs-CRP (high sensitivity C-reactive protein), PCT (procalcitonin) and acute phase proteins, will be determined before CPB, during CPB, immediately after, 24h, 48h and 5 days after CPB. We will document demographic characteristics of patients, their preoperative medical status, as well as intraoperative data (type and duration of surgery, duration of CPB, period of ischemia, hemodynamic parameters, usage of inotropic/vasoactive therapy, insulin, fluids, blood and blood components); duration of mechanical ventilation in intensive care unit (ICU), duration of ICU stay, 30-day mortality and morbidity, as well as postoperative complications (bleeding, hemodynamic instability, impaired respiratory function, infection, worsening of renal, liver and cognitive function).

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Elective complex cardiac surgery (combined valve and coronary bypass grafting surgery, concomitant valve surgery, surgery of the ascending aorta and aortic arch, as well as re-operations of the same type)
  • Age > 18 years

Exclusion criteria

  • Disagreement to participate in the study
  • Age < 18 years
  • Pregnancy
  • Emergency procedure
  • Heart transplantation
  • Implantation of LVAD (left ventricular assist device), RVAD (right ventricular assist device) or TAH (total artificial heart)
  • Treatment with chemotherapy, immunosuppressive therapy
  • Treatment with anti-leukocyte drugs or TNF-alfa blockers
  • Immunocompromised patients (AIDS), leucopenia (< 4,0x109 / L)
  • Clinical and/or laboratory signs of infection (CRP >2 mg/dl)
  • Serum creatinine >2 mg/dl
  • Bilirubin >2 mg/dl
  • History of stroke
  • Malnourished patients, BMI < 18

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

60 participants in 3 patient groups

Study (CytoSorb)
Experimental group
Description:
In the study group (20 patients) the CytoSorb filter will be installed in the CPB in a parallel circuit. An additional roller pump will drive the blood through the filter with a constant flow of 400 ml/min (max flow).
Treatment:
Device: CytoSorb
Control
No Intervention group
Description:
In the control group (20 patients) no filter will be installed on the CPB.
Corticosteroid
Active Comparator group
Description:
In the corticosteroid group (20 patients), 1 gram of methylprednisolone will be added in the priming solution of CPB machine. No filter will be installed on the CPB.
Treatment:
Drug: Methylprednisolone

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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