Heart Failure
Conditions
Keywords
cardiac surgery, inflammation, cytokines, bypass, artificial heart known as LVAD
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.
Interventions
DEVICECytoSorb 300 mL device
Intra-and postoperative CytoSorb hemoadsorption
Sponsors
UMC Utrecht
CytoSorbents, Inc
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Increase in plasma IL-6 concentration | from baseline to the time of arrival to intensive care unit (approximately 4 hours). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From Baseline through ICU discharge (approximately 7 days) | Ratio of eligible patients and those receiving study intervention |
| Incidence and progression of vasoplegia | from baseline to 24 hours after surgery | 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) |
| Prevalence of right ventricle dysfunction | From baseline to 72 hours after surgery | Transesophageal echocardiography indices of right ventricle dysfunction based on TAPSE, estimates of the RV-PA coupling, 3D volumetry and ventricle free wall strain |
| Incidence and progression of Acute Kidney Injury (KDIGO criteria) | From Baseline through ICU discharge (approximately 7 days) | — |
| Prevalence of liver dysfunction | from baseline to 72 hours after surgery | 14\. Defined as changes in indocyanine green plasma disappearance rate masured by the LiMON® monitor |
| Sequential Organ Failure Assessment Score (SOFA) | From Baseline through ICU discharge (approximately 7 days) | Total Daily SOFA Score. The score ranges from 0 (best outcome) to 24 (worst outcome). |
| Time of mechanical ventilation | From Baseline through ICU discharge (approximately 7 days) | Duration of invasive mechanical ventilation |
| Length of ICU stay | From Baseline through ICU discharge (approximately 7 days) | — |
| 28 day mortality | 28 days after surgery | — |
| 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 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in inflammasome analyses | from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days | Plasma and urinary levels of the inflammatory mediators: IL-1β,IL-1Ra, IL-6, IL-8, IL-10, TNF-α, MPO and HBP \[pg/ml for all\] |
| Changes in the metabolomics profile | from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days | Changes in the metabolomics profile (fold changes) measured by LC-MS and NMR platforms |
Countries
United Kingdom
Contacts
Primary ContactNandor Marczin
Backup ContactEric EC de Waal
Outcome results
None listed