CYtosorb modulation of surgiCal infLammatiON during LVAD insErtion (CYCLONE-LVAD)

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.
We hypothesize 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.

The four 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.

A prospective randomised, two-arm, patient-blinded feasibility clinical study.

Subjects will be randomized in a 1:1 ratio to either standard of care (SOC)
alone or standard of care and treatment with the Cytosorb® device. The
haemadsorption treatment will be instituted during cardiopulmonary bypass.

The burden and risks associated with participation in this trial are limited.
Multiple studies have been performed with the haemoabsorption device and thus
far, no serious adverse events associated with Cytosorb ® have been reported.
This remains, however, a safety and feasibility experiment, since Cytosorb ®
has never been tested during the implantation of CF-LVAD. Patients will be
asked to participate in this study during their scheduled out-patient
appointment and follow-up lasts for 30 days or up until discharge (if discharge
happens earlier than 30 days postoperatively). No additional visits to the
hospital for the purpose of this trial are required. Diagnostic tests including
laboratory studies are mostly already part of the standard of care. For the
biobank repository part of this study, patient blood and urine will be
collected at several time-points (start of surgery, end of cardiopulmonary
bypass, at skin closure, and 6, 12, 24, 48 and 72 hours after operation), and
processed for storage in the study biobank. In order to minimise the burden to
the participating patients, material will be collected from suitable access
points that are already in place (e.a. arterial or central venous lines). Ten
ml blood will be processed in EDTA and heparin containing test tubes, and the
supernatant plasma samples will be stored in 1 ml aliquots for subsequent
biobanking and analysis.