The Effect of Vitamin E-coated Polysulfone Membrane on Oxidative Stress, Inflammation and Monocytes in Critically Ill Patients in CRRT (Vitabrane E)

The Effect of Vitamin E-coated Polysulfone Membrane on Oxidative Stress, Inflammation and Monocytes in Critically Ill Patients in CRRT: a Pilot, Randomized, Double-blinded, No-profit, Clinical Study

The study evaluate the effect of a membrane in polysulfone covered with vitamin E (ViE15-A, ASAHI Kasey, Tokyo, Japan) versus non-vitamin E polysulfone membrane (REXEED-15A, ASAHI Kasey, Tokyo, Japan) in critically ill patients admitted to intensive care undergoing continuous extracorporeal dialysis (CRRT).

The current randomized study is designed to assess the effect on the levels of oxidative stress, pro and anti-inflammatory cytokines and the mode and amount of death of monocytic cell lines using ViE 15-A in comparison withe REXEED-15A.

The investigators hypothezise that the ViE15-A versus REXEED-15A will have different effect on the levels of oxidative stress, pro and anti-inflammatory cytokines and the mode and amount of death of monocytic cell lines.

Study Overview

• Status: Unknown
• Conditions: Renal Failure; Renal Insufficiency, Acute
• Intervention / Treatment: Device: ViE15-A; Device: REXEED-15A

Detailed Description

The study evaluate the effect of a membrane in polysulfone covered with vitamin E (ViE15-A, ASAHI Kasey, Tokyo, Japan) on the levels of oxidative stress, pro and anti-inflammatory cytokines and the mode and amount of death of monocytic cell lines in critically ill patients admitted to intensive care undergoing continuous extracorporeal dialysis (CRRT).

This membrane will be compared with a non-vitamin E polysulfone membrane (REXEED-15A, ASAHI Kasey, Tokyo, Japan) and already intended for use in continuous renal support therapy.

The current randomized study is designed to assess the effect on the levels of oxidative stress, pro and anti-inflammatory cytokines and the mode and amount of death of monocytic cell lines using ViE 15-A in comparison withe REXEED-15A.

Precisely, will be evaluated

1. the effect of the filter on the reduction of the plasma levels of two pro-inflammatory cytokines (IL-1β and IL-6) and of two anti-inflammatory cytokines (IL-10, IL-8);
2. the analysis of the life modality of the monocytic cells: the patient's plasma will be used, incubated for 24 hours with U937 cells (monocyte precursor cells), necrosis cells and the percentage of apoptotic cells. The apoptotic cells will also evaluate the apoptotic pathway (evaluation of activated caspases) that led to cell death. The differences that are highlighted in the two different sampling moments become expressed Δ% with respect to the initial value Secondary outcomes will be to evaluate the clinical outcomes (haemodynamic and hematochemical parameters) in the short and long term deriving from the application of a membrane with vitamin E; for this reason, for the whole duration of the extracorporeal dialysis therapy, the same filter assigned to the patient at the time of enrollment will be used.

All the other parameters of the extracorporeal treatment that can influence the results will be standardized; in particular, the flows will be fixed according to the dialysis dose criteria and re-infusion methods according to the table in the paragraph "treatment characteristics".

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

Contacts and Locations

Study Locations

• Italy
  • Vicenza, Italy, 36100
    • Recruiting
    • San Bortolo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Acute Kidney Injury
• ICU patients with clinical indication for Continuous Renal Replacement Therapy
• Clinical decision to begin CVVH for at least 24 hours with high flux filter (defined as membranes with an ultrafiltration coefficient KUF > 25ml/Kg/h)
• Obtain the informed consent

Exclusion Criteria:

• Hemodialysis patients, peritoneal dialysis patients and transplant recipient;
• Hypothermia (T < 36°C)
• Regional Anticoagulation with Citrate
• Septic Shock;
• Neoplasm in Chemotherapy
• Extra-Corporeal Membrane Oxygenation
• Cardio Circulatory Arrest
• Autoimmune disease or immunosuppressed patients;
• Life expectancy < 24 hr
• Pregnancy;
• Informed Consent refused by the patient or surrogate decision-maker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ViE15-A; The patients were randomly allocated to two groups by using computer-generated numbers. The renal replacement therapy will be started using ViE15-A hemofilter	Device: ViE15-A; The type of dialytic treatment that will be used during the study will be continuous venous hemofiltration (CVVH-Continuous veno-venous hemofiltration). The filter will be ViE15-A.
Active Comparator: REXEED-15A; TThe patients were randomly allocated to two groups by using computer-generated numbers. The renal replacement therapy will be started using REXEED-15A	Device: REXEED-15A; The type of dialytic treatment that will be used during the study will be continuous venous hemofiltration (CVVH-Continuous veno-venous hemofiltration). The filter will be REXEED-15A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Copper/Zinc	In vivo comparison of ROS concentrations in two groups	change from 24 to 72 hours
Superoxide Dismutas	In vivo comparison of ROS concentrations in two groups	change from 24 to 72 hours
Endogenous peroxidase activity	In vivo comparison of ROS concentrations in two groups	change from 24 to 72 hours
Nitric Oxide	In vivo comparison of ROS concentrations in two groups	change from 24 to 72 hours
Viability	Ex vivo comparison of relative decrease of monocytes cell line incubated in plasma	change from 24 to 72 hours
Apoptosis	Ex vivo comparison of relative decrease of monocytes cell line incubated in plasma	change from 24 to 72 hours
Necrosis	Ex vivo comparison of relative decrease of monocytes cell line incubated in plasma	change from 24 to 72 hours
Interleukine-6	In vivo comparison of relative reductions of inflammatory cytokines concentrations in two groups	change from 24 to 72 hours
Interleukine -10	In vivo comparison of relative reductions of inflammatory cytokines concentrations in two groups	change from 24 to 72 hours
Interleukine-18	In vivo comparison of relative reductions of inflammatory cytokines concentrations in two groups	change from 24 to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of CRRT-free days from enrollment to ICU discharge in two groups	The assessment of the effect of both hemofilters on short term clinical renal outcomes	7 days
Comparison of mechanical Ventilation-free days from enrollment to ICU discharge in two groups	The assessment of the effect of both hemofilters on short term clinical renal outcomes	7 days
Comparison of vasopressor drugs-free days in two groups	The assessment of the effect of both hemofilters on short term clinical renal outcomes	7 days
Comparison of ICU length of stay in two groups	The assessment of the effect of both hemofilters on short term clinical renal outcomes	7 days
Comparison of renal recovery in two groups	The assessment of the effect of both hemofilters on short term clinical renal outcomes	7 days
Comparison of CRRT-free days from enrollment to hospital discharge in two groups	The assessment of the effect of both hemofiltes on long term clinical renal outcomes	90 days
Comparison of need of (Intermittent Hemodialysis) IHD at hospital discarge in patients treated with vitamine E-coated membrane and non-vitamin E-coated membrane	The assessment of the effect of both hemofiltes on long term clinical renal outcomes	90 days
Comparison of renal recovery at hospital discharge in two groups	The assessment of the effect of both hemofiltes on long term clinical renal outcomes	90 days

Collaborators and Investigators

• Sponsor: St. Bortolo Hospital
• Investigators: Study Director: Claudio Ronco, MD, Department of Nephrology, Dialysis and Transplantation

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2018
• Primary Completion (Actual): September 13, 2018
• Study Completion (Anticipated): December 13, 2019

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (Actual): April 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Oxidative Stress; Acute Kidney Injury; Renal Replacement Therapy; Vitamine E-coated Polysulfone Membrane
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Inflammation; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 79/16A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No