Improvement of EPO-resistance in Hemodialysis Patients With Chronic Inflammation by High Cut-off Hemodialysis (CIEPO-PILOT)

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

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.

Study Overview

• Status: Completed
• Conditions: End-Stage Renal Disease (ESRD)
• Intervention / Treatment: Device: Theralite (high cut-off hemodialysis); Device: Conventional high-flux dialyzer

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan
    • Bollate, Milan, Italy, 20021
      • Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vantive Health LLC
• Collaborators: Baxter Healthcare Corporation; Gambro Dialysatoren GmbH
• Investigators: Principal Investigator: Ugo Teatini, Dr., Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: February 2, 2012
• First Submitted That Met QC Criteria: February 2, 2012
• First Posted (Estimated): February 6, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: hemodialysis; End-Stage Renal Disease (ESRD); chronic Inflammation; EPO Resistance; ESA Resistance; high cut-off dialysis
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Inflammation; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: No 1491 CIEPO-PILOT