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

Phase 1

Completed

• Conditions: Chronic Kidney Failure; Dialysis Related Complication
• Interventions: Procedure: mixed on-line hemodiafiltration; Procedure: High flux bicarbonate dialysis

• Registration Number: NCT03202212
• Lead Sponsor: A.O.U. Città della Salute e della Scienza

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.

Study Timeline

• Study Start: 2014-02-03
• Primary Completion: 2014-02-10
• Study Completion: 2014-11-11
• Status Verified: 2017-06
• Study First Submitted: 2017-06-08
• Study First Submitted QC: 2017-06-26
• Last Update Submitted: 2017-06-27
• Study First Posted: 2017-06-28
• Last Update Posted: 2017-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mixed on-line hemodiafiltration	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
High flux bicarbonate dialysis	High flux bicarbonate dialysis	Standard high flux bicarbonate dialysis with polysulfone membrane, three sessions per week, four hours per session

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Città della Salute e Della Scienza di Torino - Presidi CTO e Molinette; 🇮🇹 Torino, To, Italy