Clinical trial NCT04596813: Role of Cytosorb in Left Ventricular Assist Device Implantation
Official title: CYtosorb Modulation of surgiCal infLammatiON During LVAD insErtion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Keywords: cardiac surgery
inflammation
cytokines
bypass
artificial heart known as LVAD
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: CytoSorbents, Inc
First posted: 2020-10-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

1. To investigate the efficacy of Cytosorb® treatment in attenuating perioperative changes in IL-6 during CF-LVAD implantation
2. To investigate the feasibility, and safety of Cytosorb® treatment during CF-LVAD implantation.
3. 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).
4. 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.

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

Primary outcomes:
measure: Increase in plasma IL-6 concentration
timeFrame: from baseline to the time of arrival to intensive care unit (approximately 4 hours).
Secondary outcomes:
measure: Changes in IL-6 concentrations at various time points after surgery until ICU discharge
timeFrame: from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days
measure: Incidence of serious device related adverse events from the time of enrolment through ICU discharge
timeFrame: from the time of enrolment through ICU discharge (approximately 7 days)
measure: Feasibility based on number of patients eligible and receiving study intervention
timeFrame: From Baseline through ICU discharge (approximately 7 days)
measure: Incidence and progression of vasoplegia
timeFrame: from baseline to 24 hours after surgery
measure: Prevalence of right ventricle dysfunction
timeFrame: From baseline to 72 hours after surgery
measure: Incidence and progression of Acute Kidney Injury (KDIGO criteria)
timeFrame: From Baseline through ICU discharge (approximately 7 days)
measure: Prevalence of liver dysfunction
timeFrame: from baseline to 72 hours after surgery
measure: Sequential Organ Failure Assessment Score (SOFA)
timeFrame: From Baseline through ICU discharge (approximately 7 days)
measure: Time of mechanical ventilation
timeFrame: From Baseline through ICU discharge (approximately 7 days)
measure: Length of ICU stay
timeFrame: From Baseline through ICU discharge (approximately 7 days)
measure: 28 day mortality
timeFrame: 28 days after surgery
Other outcomes:
measure: Changes in inflammasome analyses
timeFrame: from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days
measure: Changes in the metabolomics profile
timeFrame: from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days
Locations:
city: Harefield
country: United Kingdom
facility: Harefield Hospital
Study officials:
affiliation: Imperial College London
name: Nandor Marczin, MD PhD
role: STUDY_CHAIR
affiliation: UMC Utrecht
name: Eric EC de Waal
role: PRINCIPAL_INVESTIGATOR
References: