Role of Cytosorb in Left Ventricular Assist Device Implantation

Study Overview
=================
Brief Summary
-----------------
Mechanical circulatory support, specifically implantable continuous flow left ventricular assist device (CF-LVAD) therapy has been established as a viable treatment for rapidly deteriorating patients suffering from end stage heart failure either as bridge or alternative to heart transplantation. However, a large proportion of these patients experience severe complications in the early postoperative period including right ventricular failure or multi organ failure leading to increased mortality. The leading theory explaining these complications involves exaggerated systemic inflammatory response prior to, during and early after CF-LVAD insertion. Among the cytokines IL-6 appears to play a major role. There is increasing demonstration of the efficacy of a cytokine haemoadsorption (HA) technology in attenuating cytokine response and particularly IL-6 in various inflammatory states and emerging data on the safety of the Cytosorb® device in routine and complex cardiac surgery. The study team hypothesizes that Cytosorb® treatment is feasible and safe in heart failure patients undergoing LVAD insertion and that it is effective in attenuating IL-6 secretion with benefit in the wider inflammatory and metabolic response to this high-risk surgery.

Detailed Description
-----------------
The principle objectives of this study are: To investigate the efficacy of Cytosorb® treatment in attenuating perioperative changes in IL-6 during CF-LVAD implantation To investigate the feasibility, and safety of Cytosorb® treatment during CF-LVAD implantation. To pilot the effect of Cytosorb® treatment on vasoplegia and organ dysfunction with specific focus on right ventricle failure, liver failure and acute kidney injury (AKI). To establish a collaborative biobank of patient's biological samples to allow extensive characterisation of patient phenotype prior to CF-LVAD implantation and their individual inflammatory and metabolic responses to surgery and perioperative management.

Official Title
-----------------
CYtosorb Modulation of surgiCal infLammatiON During LVAD insErtion

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Device: CytoSorb 300 mL device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients (≥18 years), but ≤70 years; Scheduled for elective LVAD implantation with the use of cardiopulmonary bypass; Written informed consent for participation Exclusion Criteria: Poor spoken and/or written language comprehension Declined or missing informed consent LVAD implant planned without use of CPB Total Artificial Heart implantation Planned CPB temperature < 32 °C AIDS with a CD4 count of < 200/μL Severe thrombocytopenia (PLT <50000 Application of contrast medium on the day of surgery Immunosuppressive therapy or long-term therapy with corticosteroids Contraindication to anticoagulation with heparin Participation in another clinical intervention trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard of care<br> | |
| Active Comparator: standard of care and treatment with the Cytosorb® device<br> | Device: CytoSorb 300 mL device<br>* Intra-and postoperative CytoSorb hemoadsorption<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in plasma IL-6 concentration |  | from baseline to the time of arrival to intensive care unit (approximately 4 hours). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in IL-6 concentrations at various time points after surgery until ICU discharge |  | from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days | 
| Incidence of serious device related adverse events from the time of enrolment through ICU discharge |  | from the time of enrolment through ICU discharge (approximately 7 days) | 
| Feasibility based on number of patients eligible and receiving study intervention | Ratio of eligible patients and those receiving study intervention | From Baseline through ICU discharge (approximately 7 days) | 
| Incidence and progression of vasoplegia | Defined as haemodynamic instability fulfilling the following criteria for at least three consecutive hours during the first 48h after ICU arrival: MAP ≤50 mmHg or SVR ≤800 dynes·s·cm- 5; CI ≥ 2.5 l·min- 1·m- 2; use of norepinephrine ≥200 ng·kg- 1·min- 1 or equivalent doses of vasopressors (epinephrine ≥200 ng·kg- 1·min- 1; dopamine ≥30 μg·kg- 1·min- 1; phenylephrine ≥2 μg·kg- 1·min- 1, or vasopressin ≥0.08 U·min- 1) | from baseline to 24 hours after surgery | 
| Prevalence of right ventricle dysfunction | Transesophageal echocardiography indices of right ventricle dysfunction based on TAPSE, estimates of the RV-PA coupling, 3D volumetry and ventricle free wall strain | From baseline to 72 hours after surgery | 
| Incidence and progression of Acute Kidney Injury (KDIGO criteria) |  | From Baseline through ICU discharge (approximately 7 days) | 
| Prevalence of liver dysfunction | 14. Defined as changes in indocyanine green plasma disappearance rate masured by the LiMON® monitor | from baseline to 72 hours after surgery | 
| Sequential Organ Failure Assessment Score (SOFA) | Total Daily SOFA Score. The score ranges from 0 (best outcome) to 24 (worst outcome). | From Baseline through ICU discharge (approximately 7 days) | 
| Time of mechanical ventilation | Duration of invasive mechanical ventilation | From Baseline through ICU discharge (approximately 7 days) | 
| Length of ICU stay |  | From Baseline through ICU discharge (approximately 7 days) | 
| 28 day mortality |  | 28 days after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bypass, cardiac surgery, inflammation, cytokines, artificial heart known as LVAD