Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05610683 |
| Other study ID # |
E-FLUX |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 14, 2023 |
| Est. completion date |
January 31, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Poitiers University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
