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Comparison of the Removal of Uremic Toxins With Medium Cut-off and Super High-flux Vitamin E-coated Dialyzers (E-FLUX)

Primary Purpose

End Stage Renal Disease (ESRD)

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Hemodialysis sessions using SHFVE dialyzer (VieX™) or the MCO (Theranova 500™) dialyzer
Sponsored by
Poitiers University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for End Stage Renal Disease (ESRD) focused on measuring super high-flux hemodialysis, medium cut-off hemodialysis, beta2-microglobulin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed informed consent Age ≥ 18 years Patients established on HF-HD trice weekly four hour-sessions for at least 3 months Exclusion Criteria: Malabsorption syndrome, active malignant disease or other critical illnesses and any ongoing condition that may interfere with inflammatory parameters (baseline C-Reactive Protein >40 mg/l) Pregnant or breast feeding women Any uncontrolled medical condition, psychiatric disorder or biological abnormality that might interfere with subject's participation or ability to sign an informed consent. Significant residual kidney function as defined by an urine output > 500 mL.

Sites / Locations

  • CHU de PoitiersRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

SHFVE-HD group

MCO-HD group

Arm Description

Hemodialysis sessions using the VieX™ (Polysulfone, surface area: 2.1 m², sterilization gamma, ultrafiltration coefficient: 104.3 ml/h/mmHg, Asahi Kasei Medical, Japan).

Hemodialysis sessions using the Theranova 500™ (Baxter healthcare Corporation Deerfield, USA; surface area 2 m², ultrafiltration coefficient: 59 ml/h/mmHg).

Outcomes

Primary Outcome Measures

Beta2-microglobulin reduction ratio (RR) after 3 months of SHFVE-HD and MCO-HD in a non-inferiority fashion.

Secondary Outcome Measures

Full Information

First Posted
October 27, 2022
Last Updated
June 19, 2023
Sponsor
Poitiers University Hospital
Collaborators
Hemotech
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1. Study Identification

Unique Protocol Identification Number
NCT05610683
Brief Title
Comparison of the Removal of Uremic Toxins With Medium Cut-off and Super High-flux Vitamin E-coated Dialyzers
Acronym
E-FLUX
Official Title
Comparison of the Removal of Uremic Toxins With Medium Cut-off and Super High-flux Vitamin E-coated Dialyzers The E-FLUX Randomized Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2023 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Poitiers University Hospital
Collaborators
Hemotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
End-stage renal disease (ESRD) induces an accumulation of uremic toxins responsible for increased morbidity and mortality. These toxins cover a wide range of molecules, classified according to their molecular weight as small-size (< 500 Da), middle-size (500 Da-60 kDa), and protein-bound toxins. Specific complications have been associated with the accumulation of middle-size toxins, including beta2-microglobulin (12 kDa), myoglobin (17 kDa), prolactin (23 kDa), alpha1-microglobulin (33 kDa), alpha1-glycoprotein (44 kDa), kappa (22 kDa) and lambda (45 kDa) free light chains (FLC). Moreover, mediators of oxidative stress such as asymmetric dimethylarginine, malondialdehyde, oxidative-LDL and inflammatory cytokines such as Interleukin-6 (IL)-6, IL1-β, TNF-α have been involved in atherosclerosis, malnutrition, cardiovascular events and mortality. Hemodialysis (HD) remains the main standard modality of renal replacement therapy in ESRD. In the past decade, low-flux hemodialysis was most commonly used, providing effective clearance of small solutes through diffusion, but negligible clearance of middle molecules. This limitation was insufficiently improved by the development of high-flux (HF) dialyzers due to their cut-off pores size values of approximately 15-20 kDa. In fact, most of middle molecules cannot be efficiently removed by HF-HD because of their molecular radii larger than that of membrane pores. Thus, HF dialyzers were used in post dilution on-line hemodiafiltration (OL-HDF) mode with high convection volumes and achieved greatest clearance of middle molecules. However, OL-HDF is generally not available in most HD centers and needs additional hardware technology. Therefore, several super high-flux (SHF) dialyzers integrating higher cut-off size pore value and achieving Beta2-microglobulin clearance > 70 ml/min were developed for HD mode. These SHF dialyzers used in HD (SHF-HD) provides similar middle molecules depuration compared to OL-HDF. The recently developed medium cut-off (MCO) dialyzer (Theranova 500™, Baxter healthcare Corporation Deerfield, USA; surface area 2 m², ultrafiltration coefficient: 59 ml/h/mmHg) differs from conventional HF membranes by higher and controlled porosity resulting in a steep sieving curve with a cut-off value approaching that of albumin. MCO-HD has demonstrated efficient depuration of middle uremic toxins as compared to HF-HD, similar to that of OL-HDF. MCO-HD and SHF-HD are two new large pore size dialyzers currently used nowadays in HD. In addition, the interaction between blood and membrane surface play a key role in generating oxidative stress and inflammation. Antioxidants such as vitamin E work by inhibiting LDL oxidation and by limiting cellular response to oxidized LDL. In HD patients, vitamin E may be integrated as a part of the HD procedure in the form of bioreactive dialysis membranes, in which the blood surface has been modified with alpha-tocopherol. Dialysis with vitamin E-coated membranes has been associated with an improvement in biocompatibility including circulating lipid peroxidation biomarkers and cytokine induction. In small studies, vitamin E coated dialyzers have been associated with reduced red blood count fragility and improvements in erythropoietin resistance index and erythropoietin requirements in HD. VieX (Polysulfone, surface area: 2.1 m², sterilization gamma, ultrafiltration coefficient: 104.3 ml/h/mmHg, Asahi Kasei Medical, Japan), a novel SHF vitamin E-coated (SHVE) dialyzer, which has larger pore size than HF dialyzer, might provide higher middle molecules removal and biocompatibility improvement. The aim of the present study was to compare the efficiency of the SHFVE dialyzer (VieX™) versus the MCO dialyzer (Theranova 500™) on the removal of beta2-microglobulin and other middle molecules in a non-inferiority fashion, and their respective effects on inflammation, oxidative stress and biocompatibility parameters.
Detailed Description
In a previous randomized study, it was found that compared to HF-HD after 3 months, MCO-HD was associated with higher middle molecules removal and significant decrease in beta2-microglobulin, oxidized low-density lipoprotein, kappa and lambda free light chain pre-dialysis levels, without change in other inflammatory and oxidative stress biomarkers. In addition, a modulation of inflammation has been demonstrated with MCO-HD in another randomized trial. After 3 months, MCO-HD was shown to downregulate the expression of the pro-inflammatory IL-6 and tumor necrosis factor (TNF) mRNA in peripheral leucocytes. Moreover, higher removal and decrease in TNF alpha level with concurrent reduced resistance to erythropoiesis stimulating agents (ESA) has been also reported with MCO-HD. VieX (Polysulfone, surface area: 2.1 m², sterilization gamma, ultrafiltration coefficient: 104.3 ml/h/mmHg, Asahi Kasei Medical, Japan), a novel SHF vitamin E-coated dialyzer, which has larger pore size than HF dialyzer, might provide also higher middle molecules removal and more biocompatibility improvement. Preliminary data demonstrate similar reduction ration of beta2-microglobulin, which is the most studied middle molecule, between MCO-HD and Super High Flux Vitamin E (SHFVE)-HD. The aim of the present study was to compare the efficiency of the SHFVE dialyzer versus the MCO dialyzer on the removal of beta2-microglobulin and other middle molecules in a non-inferiority fashion, and their respective effects on inflammation, oxidative stress and biocompatibility parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease (ESRD)
Keywords
super high-flux hemodialysis, medium cut-off hemodialysis, beta2-microglobulin

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
The E-FLUX is a prospective randomized open-label cross over study. The study will include 38 patients established on HF-HD randomly assigned to receive either 3 months of SHFVE-HD followed by 3 months of MCO-HD, or vice versa.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SHFVE-HD group
Arm Type
Experimental
Arm Description
Hemodialysis sessions using the VieX™ (Polysulfone, surface area: 2.1 m², sterilization gamma, ultrafiltration coefficient: 104.3 ml/h/mmHg, Asahi Kasei Medical, Japan).
Arm Title
MCO-HD group
Arm Type
Experimental
Arm Description
Hemodialysis sessions using the Theranova 500™ (Baxter healthcare Corporation Deerfield, USA; surface area 2 m², ultrafiltration coefficient: 59 ml/h/mmHg).
Intervention Type
Device
Intervention Name(s)
Hemodialysis sessions using SHFVE dialyzer (VieX™) or the MCO (Theranova 500™) dialyzer
Intervention Description
Patients will receive thrice weekly 4 hours hemodialysis sessions during 3 months
Primary Outcome Measure Information:
Title
Beta2-microglobulin reduction ratio (RR) after 3 months of SHFVE-HD and MCO-HD in a non-inferiority fashion.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent Age ≥ 18 years Patients established on HF-HD trice weekly four hour-sessions for at least 3 months Exclusion Criteria: Malabsorption syndrome, active malignant disease or other critical illnesses and any ongoing condition that may interfere with inflammatory parameters (baseline C-Reactive Protein >40 mg/l) Pregnant or breast feeding women Any uncontrolled medical condition, psychiatric disorder or biological abnormality that might interfere with subject's participation or ability to sign an informed consent. Significant residual kidney function as defined by an urine output > 500 mL.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mohamed BELMOUAZ, MD
Phone
+33 5 49 44 40 78
Email
mohamed.belmouaz@chu-poitiers.fr
Facility Information:
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamed BELMOUAZ, MD
Phone
+33 5 49 44 40 78
Email
mohamed.belmouaz@chu-poitiers.fr

12. IPD Sharing Statement

Learn more about this trial

Comparison of the Removal of Uremic Toxins With Medium Cut-off and Super High-flux Vitamin E-coated Dialyzers

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