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NCT Number: NCT02666703

Extracorporeal Cytokine Adsorption in Cardiac Surgery

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.

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Key information

Conditions

Cardiopulmonary Bypass

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University Medical Center

Ljubljana, 1000, Slovenia

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CytoSorb

Device

CytoSorb is a first-in-class extracorporeal cytokine adsorber, now approved in the European Union, and broadly indicated for use in any clinical situation where cytokines are elevated.

methylprednisolone

Drug

Primary outcomes

  1. Evolution of pro-inflammatory and anti-inflammatory cytokines [TNF-alfa, IL-1, IL-6, IL-8 and IL-10

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  2. Evolution of complement C5a

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  3. Evolution of CD 64 and CD 163 markers

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  4. Evolution of miRNA

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  5. Evolution of PON1, HDL and LDL

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

Secondary outcomes

  1. Changes in serum hs-CRP

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  2. Changes in serum PCT

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  3. Changes in white blood count

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

  4. Changes in serum albumin and fibrinogen

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day); only for Study group-1 h after start of CPB: 7)from blood entering CytoSorb and 8)from blood leaving CytoSorb

Other outcomes

  1. Duration of postoperative mechanical ventilation

    Time frame: duration of ICU stay, an expected average of 2 days

  2. Length of ICU stay

    Time frame: duration of ICU stay, an expected average of 2 days

  3. Use of inotropic/vasoactive drugs and insulin

    Time frame: 1) before induction of anesthesia; 2)at the end of CPB; 3) at the end of surgical procedure; 4) 24 h; 5) 48 h; 6) 5th postoperative day

    assessed by the dose - mcg/kg/min for inotropic/vasoactive drugs and IU/h for insulin

  4. Length of hospital stay

    Time frame: through study completion, an average of 1 year

  5. 30 days mortality

    Time frame: at day 30

Sponsors and collaborators

Lead sponsor

University Medical Centre Ljubljana

Other

Collaborators

  • Slovenian Research Agency

Registry information

Official study title

Immunomodulatory Effect of Extracorporeal Cytokine Adsorption in Cardiac Surgery

Acronym: IMEECCACS

Important dates

Study start
2016
Primary completion
2017
Study completion
2018
First posted
Jan 28, 2016
Registry last updated
Mar 25, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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