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

End-Stage Renal Disease (ESRD) Clinical Trial

— CIEPO-PILOT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01526798
• Other study ID #: No 1491 CIEPO-PILOT
• Status: Completed
• Phase: N/A
• First received: February 2, 2012
• Last updated: April 19, 2017
• Start date: March 2012
• Est. completion date: November 2012

Study information

• Verified date: March 2017
• Source: Baxter Healthcare Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End-Stage Renal Disease (ESRD)
• Inflammation
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Device:
• Theralite (high cut-off hemodialysis)
Hemodialysis with Theralite dialyzer alternating with standard high-flux dialyzer
• Conventional high-flux dialyzer

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi	Bollate	Milan

Sponsors (2)

Lead Sponsor	Collaborator
Baxter Healthcare Corporation	Gambro Dialysatoren GmbH

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Urea, Hepcidin, Free Light Chains, IL-6, IL-10	Pre- and post-dialysis concentration of urea, hepcidin	baseline, week 1
Secondary	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