Effect of Mixed On-line Hemodiafiltration on Circulating Markers of Inflammation and Vascular Dysfunction

On line haemodiafiltration (OL-HDF) has been shown to improve intra-dialytic hemodynamics and cardiovascular outcomes. Several potential candidates of these beneficial effects have been explored. The aim of this study was to investigate the impact of mixed OL-HDF (mOL-HDF) on different circulating mediators of vascular dysfunction.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Failure; Dialysis Related Complication
• Intervention / Treatment: Procedure: mixed on-line hemodiafiltration; Procedure: High flux bicarbonate dialysis

Detailed Description

This is an open label placebo-controlled randomized clinical trial to assess the effect of mixed OL-HDF (mOL-HDF) on different circulating mediators of vascular dysfunction.

Inclusion criteria: age > 18 yrs, hemodialytic treatment from at least 6 months (3 times for week), blood flow rate (Qb) ≥ 250 ml/min using arterovenous fistula (AVF) or permanent central venous catheter (CVC), blood creatinine clearance <5 ml/min, urine output<500 ml/die.

Exclusion criteria: neoplastic diseases, chronic autoimmune diseases, lack of consent, solid organ or bone marrow transplantation.

Safety Assessment: the use of mOL-HDF has been approved by the European Medicines Agency as routine hemodepurative technique for end stage renal disease patients. Patients were evaluated for adverse reaction at each dialysis section; investigators recorded intra and extra-dialytic adverse events.

Study Treatment, Dosage, and Route of Administration: Enrolled patients have been randomized in 2 groups: 15 patients continued high flux bicarbonate hemodialysis (BHD), whereas 15 patients switched to mixed on-line hemodiafiltration (mOL-HDF using FX 1000 CorDiax, Fresenius Medical Care, Bad Homburg, Germany) for 9 months.

Efficacy Assessments:

Main outcome variable: changes in RNA content of circulating exosome/microvesicles (at 9 months) Secondary outcomes: changes in circulating inflammatory markers (C-Reactive Protein, Neutrophil Gelatinase Associated Lipocalin, Interleukin-6, Ferritin) at 3-6 and 9 months. changes in RNA content of circulating microvesicles (at 3 and 6 months)

Study Duration: 9 months

Statistical Methods: Data have been analyzed according to an intention-to-treat approach. Statistical analysis was performed using the unpaired Student t -test, ANOVA, or Kruskal-Wallis test when appropriate. A two-sided value of p=0.05 was considered significant.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Italy
  • To
    • Torino, To, Italy, 10126
      • Città della Salute e Della Scienza di Torino - Presidi CTO e Molinette

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• hemodialytic treatment from at least 6 months (3 times for week), blood flow rate during dialysis session (Qb) ≥250 ml/min using arterovenous fistula (AVF) or permanent central venous catheter (CVC), blood creatinine clearance <5 ml/min, urine output <500 ml/die.

Exclusion Criteria:

• neoplastic diseases, autoimmune diseases, solid organ or bone marrow transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mixed on-line hemodiafiltration; Mixed on-line hemodiafiltration (mOL-HDF using FX 1000 CorDiax, Fresenius Medical Care, Bad Homburg, Germany), three sessions per week, four hours per session	Procedure: mixed on-line hemodiafiltration; This is a mixed hemodepurative technique exploiting diffusion and convection through a semi-permeable membrane. Dialysis solution is not only interfacing with blood through the membrane (as in bicarbonate hemodialysis) but it is also mixed with it with a pre- and a post- filter dilution. The same amount of fluid added to the bloodstream is then removed within the filter through an appropriate negative pressure in the dialysis solution compartment and thanks a high permeability membrane. Patients will be treated three sessions per week, four hours per session
Active Comparator: High flux bicarbonate dialysis; Standard high flux bicarbonate dialysis with polysulfone membrane, three sessions per week, four hours per session	Procedure: High flux bicarbonate dialysis; Standard high flux bicarbonate dialysis with polysulfone membrane, three sessions per week, four hours per session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RNA content of circulating particles	Quantitative micro-RNA changes in plasmatic exosomes/microvesicles assessed by quantitative real-time PCR	Study start (time 0) and study end (9 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating inflammatory markers	Quantitative changes in C-Reactive Protein, Neutrophil Gelatinase Associated Lipocalin, Interleukin-6, Ferritin	All the study timepoints: time 0 and 3, 6, 9 months
RNA content of circulating particles	Quantitative micro-RNA changes in plasmatic exosomes/microvesicles assessed by quantitative real-time PCR	All the study timepoints: time 0 and 3, 6, 9 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Città della Salute e della Scienza di Torino

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2014
• Primary Completion (Actual): February 10, 2014
• Study Completion (Actual): November 11, 2014

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 28, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Inflammation; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: 0030959 CEI/568

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the time of registration the study was already completed. IPD data will be available upon request till the study publication, then data will be enclosed within the publication as supplementary material.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No