Clinical trial NCT03489759: The Effect of Vitamin E-coated Polysulfone Membrane on Oxidative Stress, Inflammation and Monocytes in Critically Ill Patients in CRRT
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Renal Failure
Renal Insufficiency, Acute
Keywords: Acute Kidney Injury
Oxidative Stress
Renal Replacement Therapy
Vitamine E-coated Polysulfone Membrane
Lead sponsor: St. Bortolo Hospital
Sponsor class: OTHER
First posted: 2018-04-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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

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".

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

Primary outcomes:
measure: Copper/Zinc
timeFrame: change from 24 to 72 hours
measure: Superoxide Dismutas
timeFrame: change from 24 to 72 hours
measure: Endogenous peroxidase activity
timeFrame: change from 24 to 72 hours
measure: Nitric Oxide
timeFrame: change from 24 to 72 hours
measure: Viability
timeFrame: change from 24 to 72 hours
measure: Apoptosis
timeFrame: change from 24 to 72 hours
measure: Necrosis
timeFrame: change from 24 to 72 hours
measure: Interleukine-6
timeFrame: change from 24 to 72 hours
measure: Interleukine -10
timeFrame: change from 24 to 72 hours
measure: Interleukine-18
timeFrame: change from 24 to 72 hours
Secondary outcomes:
measure: Comparison of CRRT-free days from enrollment to ICU discharge in two groups
timeFrame: 7 days
measure: Comparison of mechanical Ventilation-free days from enrollment to ICU discharge in two groups
timeFrame: 7 days
measure: Comparison of vasopressor drugs-free days in two groups
timeFrame: 7 days
measure: Comparison of ICU length of stay in two groups
timeFrame: 7 days
measure: Comparison of renal recovery in two groups
timeFrame: 7 days
measure: Comparison of CRRT-free days from enrollment to hospital discharge in two groups
timeFrame: 90 days
measure: Comparison of need of (Intermittent Hemodialysis) IHD at hospital discarge in patients treated with vitamine E-coated membrane and non-vitamin E-coated membrane
timeFrame: 90 days
measure: Comparison of renal recovery at hospital discharge in two groups
timeFrame: 90 days
Other outcomes:
Locations:
city: Vicenza
country: Italy
facility: San Bortolo Hospital
Study officials:
affiliation: Department of Nephrology, Dialysis and Transplantation
name: Claudio Ronco, MD
role: STUDY_DIRECTOR
References: