Collaborative Research on HFR High Flux

Inflammation Clinical Trial

— SALATO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01492491
• Other study ID #: CRC-01
• Secondary ID: ASLCagliariPBola
• Status: Completed
• Phase: Phase 3
• First received: December 10, 2011
• Last updated: June 13, 2016
• Start date: September 2011
• Est. completion date: March 2013

Study information

• Verified date: June 2016
• Source: Azienda Sanitaria Locale di Cagliari
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Inflammation

Intervention

Device:
• SUPRA-HFR
usual dialytic prescription for duration, frequency, acid buffer and anticoagulation regimen.

Locations

Country	Name	City	State
Italy	Nephrology and dialysis, SS. Trinità Hospital	Cagliari
Italy	Territorial dialysis service, Regional Health system nephrology and dialysis department	Cagliari
Italy	Nephrology and dialysis, Civil Hospital	La Maddalena
Italy	Nephrology and dialysis, Civil Hospital	Lanusei
Italy	Nephrology and dialysis department, Versilia Hospital	Lido di Camaiore
Italy	Nephrology and dialysis department, Civil Hospital	Macomer
Italy	Nephrology and dialysis, San Francesco Hospital	Nuoro
Italy	Nephrology and dialysis, San Martino Hospital	Oristano
Italy	Nephrology and dialysis department, Bonaria Hospital	San Gavino Monreale
Italy	Nephrology and dialysis, San Camillo Hospital	Sorgono
Italy	Nephrology and dialysis, Dettori Hospital	Tempio

Sponsors (3)

Lead Sponsor	Collaborator
Azienda Sanitaria Locale di Cagliari	Bellco s.r.l., Istituto Superiore di Sanità

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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. — View Citation

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. Epub 2005 Nov 22. — View Citation

Wratten ML, Ghezzi PM. Hemodiafiltration with endogenous reinfusion. Contrib Nephrol. 2007;158:94-102. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	amelioration of the anemia management	evaluation of ESAs dose, Hb level	1 year	No