Collaborative Research on HFR High Flux (SALATO)

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation
• Intervention / Treatment: Device: SUPRA-HFR

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Cagliari, Italy, 09045
    • Territorial dialysis service, Regional Health system nephrology and dialysis department
  • Cagliari, Italy, 09132
    • Nephrology and dialysis, SS. Trinità Hospital
  • La Maddalena, Italy, 07024
    • Nephrology and dialysis, Civil Hospital
  • Lanusei, Italy, 08045
    • Nephrology and dialysis, Civil Hospital
  • Lido di Camaiore, Italy, 55041
    • Nephrology and dialysis department, Versilia Hospital
  • Macomer, Italy, 08015
    • Nephrology and dialysis department, Civil Hospital
  • Nuoro, Italy, 08100
    • Nephrology and dialysis, San Francesco Hospital
  • Oristano, Italy, 09170
    • Nephrology and dialysis, San Martino Hospital
  • San Gavino Monreale, Italy, 09037
    • Nephrology and dialysis department, Bonaria Hospital
  • Sorgono, Italy, 08038
    • Nephrology and dialysis, San Camillo Hospital
  • Tempio, Italy, 07029
    • Nephrology and dialysis, Dettori Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azienda Sanitaria Locale di Cagliari
• Collaborators: Istituto Superiore di Sanità; Bellco s.r.l.
• Investigators: Principal Investigator: Piergiorgio Bolasco, MD, Azienda Sanitaria Locale di Cagliari

Publications and helpful links

General Publications

• Wratten ML, Ghezzi PM. Hemodiafiltration with endogenous reinfusion. Contrib Nephrol. 2007;158:94-102. doi: 10.1159/000107239.
• Bolasco PG, Ghezzi PM, Serra A, Corazza L, Murtas S, Mascia M, Cossu M, Ferrara R, Cogoni G, Cadinu F, Casu D, Contu B, Passaghe M, Ghisu T, Ganadu M, Logias F. Hemodiafiltration with endogenous reinfusion with and without acetate-free dialysis solutions: effect on ESA requirement. Blood Purif. 2011;31(4):235-42. doi: 10.1159/000322400. Epub 2011 Jan 14.
• Panichi V, Manca-Rizza G, Paoletti S, Taccola D, Consani C, Filippi C, Mantuano E, Sidoti A, Grazi G, Antonelli A, Angelini D, Petrone I, Mura C, Tolaini P, Saloi F, Ghezzi PM, Barsotti G, Palla R. Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial. Nephrol Dial Transplant. 2006 Mar;21(3):756-62. doi: 10.1093/ndt/gfi189. Epub 2005 Nov 22.
• Palleschi S, Ghezzi PM, Palladino G, Rossi B, Ganadu M, Casu D, Cossu M, Mattana G, Pinna AM, Contu B, Ghisu T, Monni A, Gazzanelli L, Mereu MC, Logias F, Passaghe M, Amore A, Bolasco P; Sardinian Study Group. Vitamins (A, C and E) and oxidative status of hemodialysis patients treated with HFR and HFR-Supra. BMC Nephrol. 2016 Aug 26;17(1):120. doi: 10.1186/s12882-016-0315-6.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 10, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 15, 2011

Study Record Updates

• Last Update Posted (Estimate): June 14, 2016
• Last Update Submitted That Met QC Criteria: June 13, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: SUPRA-HFR; adsorpition; vitamins; large toxins
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: CRC-01; ASLCagliariPBolascosolismo52 (Registry Identifier: 231152PBolasco)