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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Chronic Kidney Failure, Dialysis Related Complication

Intervention / Treatment
-----------------
* Procedure: mixed on-line hemodiafiltration
* Procedure: High flux bicarbonate dialysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 30 patients treated with a standard 3-time per week bicarbonate high-flux hemodialysis will be randomized 1:1 to continue the treatment or to be switched to mixed on-line hemodiafiltration for 9 months
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixed on-line hemodiafiltration<br>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<br>* 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<br>|
| Active Comparator: High flux bicarbonate dialysis<br>Standard high flux bicarbonate dialysis with polysulfone membrane, three sessions per week, four hours per session | Procedure: High flux bicarbonate dialysis<br>* Standard high flux bicarbonate dialysis with polysulfone membrane, three sessions per week, four hours per session<br>|

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 |