Collaborative Research on HFR High Flux

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the serum concentrations of antoxidant vitamines A, C, E, inflammatory cytokines and middle-large toxins in patients treated with online hemodiafiltration, standard HFR and SUPRA-HFR.

Detailed Description
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Today, as the research work of EUTOX group highlights, large cytokines and protein-bound solutes are gaining a relevant attention because of their emerging role as mortality predictors. Online hemodiafiltration (online HDF) has demonstrated to offer a significant depuration for small and middle toxins, but removal of protein-bound solutes is scarce. Synthetic high-flux membranes do not allow infact significant removal of molecules heavier than 15-20 KDa. Super-flux membranes may enhance online HDF convective transport but it would surely expose the patient to unacceptable losses of albumin, vitamines and aminoacids because of the non selectivity of the convective transport. HFR is a renal replacement therapy that utilizes convection, diffusion and adsorption. It uses a double-stage filter that consists of a high-flux polyethersulfone hemofilter in the first convective stage and a low-flux polyethersulfone filter in the second diffusive stage. The stages of the filter allow complete separation of convection from diffusion. The convective part of the first stage allows pure ultrafiltrate (UF) to pass through a sorbent resin cartridge. The first convective/adsorption stage has no net fluid removal. The blood and reinfused clean UF then undergo traditional dialysis. The second stage works by classicaHD and in this final stage the weight loss occurs. HFR has demonstrated in various clinical trials to reduce the microinflammatory state with no albumin loss and minimal aminoacids losses, thanks to the high selectivity of the resin sorbent. SUPRA-HFR is a newly developed HDF therapy based on the HFR concept scheme, which includes a super-flux membrane in the first section, coupled with an empowered resin sorbent. This should significantly enhance large solutes depuration, overcoming online HDF flaws. Therefore we proposed a prospective, multicenter, randomized study comparing online HDF, standard HFR and SUPRA-HFR. After a wash-out stabilization period of 4 months in post-dilution online HDF, an expected number of 50 patients will be randomized either in standard HFR (25) or in SUPRA-HFR (25) and followed for 6 months. Primary end points focus on the the removal of protein-bound solutes, inflammation and nutritional state. In addition, ESAs doses and hemoglobin levels will be assessed and compared between treatment groups. This study will provide strong evidence on the safe and clinically effective use of super-flux membranes, introduced with SUPRA-HFR therapy. It is highly likely that the outcomes of this study will affect the daily clinical practice of Italian and European dialysis centers because of the potential innovation brought to the market. The following hypotheses will be tested: SUPRA-HFR selectivity will reduce consistently the albumin, aminoacids and vitamines A, C, E losses compared to online HDF. SUPRA-HFR better preservation of the nutritional parameters, coupled with the possibility to remove protein-bound toxins and cytokines should lead to a higher reduction of the microinflammatory status, compared to online HDF and to standard HFR. SUPRA-HFR impact on inflammation status should ameliorate the anemia management by reducing the administered ESAs doses.

Official Title
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Collaborative Study on Outcome of Antioxidant Vitamines, Microinflammation Parameters and Middle-high Toxins in ESRD Patients Treated With Online HDF, HFR and SUPRA-HFR

Conditions
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Inflammation

Intervention / Treatment
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* Device: SUPRA-HFR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: dialysis vintage > 6 months well functioning vascular access (QB > 300 mL/min) informed consent given Exclusion Criteria: polycystic kidney disease (PKD) significant acute or chronic inflammatory comorbidities non-renal related anemia blood transfusions in the last 2 months before enrollment alcohol or drugs abuse malignant neoplasm hemoglobinopathy or myelopathy pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard HFR therapy<br>standard HFR hemodiafiltration therapy | |
| Active Comparator: SUPRA-HFR therapy<br>SUPRA-HFR hemodiafiltration therapy | Device: SUPRA-HFR<br>* usual dialytic prescription for duration, frequency, acid buffer and anticoagulation regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| selective depuration of large uraemic toxins and reduction of nutrient losses | evaluation of the serum level of albumin, antioxidant vitamins and cytokines (IL6, IL1-beta) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| amelioration of the anemia management | evaluation of ESAs dose, Hb level | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SUPRA-HFR, adsorpition, vitamins, large toxins