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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gambro Dialysatoren GmbH
ClinicalTrials.gov Identifier:
NCT01526798
First received: February 2, 2012
Last updated: March 7, 2014
Last verified: January 2013
  Purpose

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.


Condition Intervention
End-Stage Renal Disease (ESRD)
Device: Theralite (high cut-off hemodialysis)
Device: Conventional high-flux dialyzer

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Improvement of EPO-resistance in HD Patients With Chronic Inflammation by High Cut-off Hemodialysis - Pilot Study (CIEPO-PILOT)

Resource links provided by NLM:


Further study details as provided by Gambro Dialysatoren GmbH:

Primary Outcome Measures:
  • Erythropoietin (EPO) resistance index [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]
    Weekly EPO dose in international units (IU) per kg body weight divided by hemoglobin value in g/dL


Secondary Outcome Measures:
  • high sensitivity C-reactive protein (CRP), hepcidin, Free Light Chains (FLC), Interleukin (IL)-6, Interleukin (IL)-10 [ Time Frame: baseline, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
    Change in pre-dialysis concentration over study period

  • Urea, Hepcidin, Free Light Chains, IL-6, IL-10 [ Time Frame: baseline, week 1 ] [ Designated as safety issue: No ]
    Pre- and post-dialysis concentration of urea, hepcidin

  • Albumin [ Time Frame: baseline, weeks 2,4,6,8,10,12,14,16,18,20,22,24 ] [ Designated as safety issue: Yes ]
    Pre-dialysis albumin concentration during study period and follow-up


Enrollment: 24
Study Start Date: March 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therlite hemodialysis Device: Theralite (high cut-off hemodialysis)
Hemodialysis with Theralite dialyzer alternating with standard high-flux dialyzer
Active Comparator: Control group hfHDF
Control group hfHDF
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01526798

Locations
Italy
Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi
Bollate, Milan, Italy, 20021
Sponsors and Collaborators
Gambro Dialysatoren GmbH
Investigators
Principal Investigator: Ugo Teatini, Dr. Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi
  More Information

No publications provided

Responsible Party: Gambro Dialysatoren GmbH
ClinicalTrials.gov Identifier: NCT01526798     History of Changes
Other Study ID Numbers: No 1491 CIEPO-PILOT
Study First Received: February 2, 2012
Last Updated: March 7, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Gambro Dialysatoren GmbH:
End-Stage Renal Disease (ESRD)
chronic Inflammation
EPO Resistance
ESA Resistance
high cut-off dialysis
hemodialysis

Additional relevant MeSH terms:
Inflammation
Kidney Diseases
Kidney Failure, Chronic
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on September 16, 2014