Role of Cytosorb in Left Ventricular Assist Device Implantation

Heart Failure Clinical Trial

— CYCLONE-LVAD  

Official title:

CYtosorb Modulation of surgiCal infLammatiON During LVAD insErtion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04596813
• Other study ID #: 18IC4535
• Status: Recruiting
• Phase: N/A
• Start date: September 21, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: Imperial College London
• Contact: Nandor Marczin
• Phone: +44 1895 823 737
• Email: n.marczin[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Device:
• CytoSorb 300 mL device
Intra-and postoperative CytoSorb hemoadsorption

Locations

Country	Name	City	State
United Kingdom	Harefield Hospital	Harefield

Sponsors (3)

Lead Sponsor	Collaborator
Imperial College London	CytoSorbents, Inc, UMC Utrecht

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in inflammasome analyses	Plasma and urinary levels of the inflammatory mediators: IL-1ß,IL-1Ra, IL-6, IL-8, IL-10, TNF-a, 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
Other	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
Primary	Increase in plasma IL-6 concentration		from baseline to the time of arrival to intensive care unit (approximately 4 hours).
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	Incidence and progression of Acute Kidney Injury (KDIGO criteria)		From Baseline through ICU discharge (approximately 7 days)
Secondary	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
Secondary	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)
Secondary	Time of mechanical ventilation	Duration of invasive mechanical ventilation	From Baseline through ICU discharge (approximately 7 days)
Secondary	Length of ICU stay		From Baseline through ICU discharge (approximately 7 days)
Secondary	28 day mortality		28 days after surgery