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

Study Overview
=================
Brief Summary
-----------------
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.

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 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); 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.

Official Title
-----------------
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

Conditions
-----------------
Renal Failure, Renal Insufficiency, Acute

Intervention / Treatment
-----------------
* Device: ViE15-A
* Device: REXEED-15A


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ViE15-A<br>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<br>* 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.<br>|
| Active Comparator: REXEED-15A<br>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<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Kidney Injury, Oxidative Stress, Renal Replacement Therapy, Vitamine E-coated Polysulfone Membrane