Role of Cytosorb in Left Ventricular Assist Device Implantation (CYCLONE-LVAD)

CYtosorb Modulation of surgiCal infLammatiON During LVAD insErtion

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: CytoSorb 300 mL device

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nandor Marczin; Phone Number: +44 1895 823 737; Email: n.marczin@imperial.ac.uk
• Study Contact Backup: Name: Eric EC de Waal; Phone Number: +88 75 563 76; Email: e.e.c.dewaal@umcutrecht.nl

Study Locations

• United Kingdom
  • Harefield, United Kingdom
    • Recruiting
    • Harefield Hospital
    • Contact: Nandor Marczin; Phone Number: 4401895823737
    • Contact: Louise Moss; Phone Number: 4401895823737

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in inflammasome analyses	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]	from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days
Changes in the metabolomics profile	Changes in the metabolomics profile (fold changes) measured by LC-MS and NMR platforms	from baseline, 6, 12, 24, 48 and 72 hours after surgery and at ICU discharge, approximately 7 days

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: UMC Utrecht; CytoSorbents, Inc
• Investigators: Study Chair: Nandor Marczin, MD PhD, Imperial College London; Principal Investigator: Eric EC de Waal, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; inflammation; cytokines; bypass; artificial heart known as LVAD
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 18IC4535

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No