Improvement of EPO-resistance in Hemodialysis Patients With Chronic Inflammation by High Cut-off Hemodialysis

Study Overview
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Brief Summary
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Chronic inflammation in dialysis patients is linked to cardiovascular mortality and clinical signs and symptoms, like the impaired response to erythropoiesis-stimulating agents (ESAs). This study aims to demonstrate that high cut-off hemodialysis is effective in reducing chronic inflammation and thereby improving response to ESAs.

Detailed Description
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Chronic inflammation in hemodialysis patients (micro-inflammation) is caused by multiple inflammatory stimuli and becomes apparent by elevated levels of biochemical markers such as CRP, IL-6, cellular activation markers etc. Chronic inflammation is linked to clinical signs and symptoms and cardiovascular mortality in dialysis patients. Inflamed dialysis patients show impaired response to erythropoiesis-stimulating agents (ESA) related to reduced iron utilization (functional iron deficiency) and elevated CRP levels are associated with a greater need for ESA to meet hemoglobin targets. If absolute iron deficiency can been excluded, EPO resistance is likely related to 'inflammatory block'. The high molecular permeability of the Theralite high cut-off membrane allows for significant clearance of cytokines and other pro-inflammatory solutes by hemodialysis as shown in previous trials with high cut-off dialyzers. The study therefore aims to demonstrate that Theralite dialysis is effective in reducing chronic inflammation in ESRD patients, thereby improving EPO responsiveness. If this can be demonstrated, application of Theralite hemodialysis may reduce morbidity and mortality in the long term in ESRD patients.

Official Title
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Improvement of EPO-resistance in HD Patients With Chronic Inflammation by High Cut-off Hemodialysis - Pilot Study (CIEPO-PILOT)

Conditions
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End-Stage Renal Disease (ESRD)

Intervention / Treatment
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* Device: Theralite (high cut-off hemodialysis)
* Device: Conventional high-flux dialyzer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ESRD treated with chronic HD for at least 3 months Treatment with high-flux dialyzers for at least 3 months Age ≥18 years Receiving ESA to treat anemia for at least 3 months Impaired ESA responsiveness as indicated by EPO resistance index > median of patients in study center Transferrin saturation (TSAT) ≥20% (last routine value prior to randomization) Serum ferritin ≥100 ng/ml (last routine value prior to randomization) Exclusion Criteria: Acute infection ≤4 weeks prior to randomization HIV or hepatitis infection Catheter Chronic liver disease Active cancer Known blood dyscrasia (paraprotein abnormalities) Known bleeding disorders Bleeding episode ≤12 weeks prior to randomization Blood/red cell transfusion ≤12 weeks prior to randomization Hypoalbuminemia defined as serum albumin concentration below 35 g/L (last routine value prior to randomization) Participation in another clinical interventional investigation Pregnancy Inability to give informed consent Planned transplantation within study period +3 months Planned interventions requiring hospitalization >1 week

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therlite hemodialysis<br> | Device: Theralite (high cut-off hemodialysis)<br>* Hemodialysis with Theralite dialyzer alternating with standard high-flux dialyzer<br>|
| Active Comparator: Control group hfHDF<br>Control group hfHDF | Device: Conventional high-flux dialyzer<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythropoietin (EPO) resistance index | Weekly EPO dose in international units (IU) per kg body weight divided by hemoglobin value in g/dL | 12 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| high sensitivity C-reactive protein (CRP), hepcidin, Free Light Chains (FLC), Interleukin (IL)-6, Interleukin (IL)-10 | Change in pre-dialysis concentration over study period | baseline, 4, 8 and 12 weeks | 
| Urea, Hepcidin, Free Light Chains, IL-6, IL-10 | Pre- and post-dialysis concentration of urea, hepcidin | baseline, week 1 | 
| Albumin | Pre-dialysis albumin concentration during study period and follow-up | baseline, weeks 2,4,6,8,10,12,14,16,18,20,22,24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End-Stage Renal Disease (ESRD), chronic Inflammation, EPO Resistance, ESA Resistance, high cut-off dialysis, hemodialysis