Clinical trial NCT01526798: Improvement of EPO-resistance in Hemodialysis Patients With Chronic Inflammation by High Cut-off Hemodialysis
Official title: Improvement of EPO-resistance in HD Patients With Chronic Inflammation by High Cut-off Hemodialysis - Pilot Study (CIEPO-PILOT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End-Stage Renal Disease (ESRD)
Keywords: End-Stage Renal Disease (ESRD)
chronic Inflammation
EPO Resistance
ESA Resistance
high cut-off dialysis
hemodialysis
Lead sponsor: Vantive Health LLC
Sponsor class: INDUSTRY
Collaborators: name: Gambro Dialysatoren GmbH
name: Baxter Healthcare Corporation
First posted: 2012-02-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Erythropoietin (EPO) resistance index
timeFrame: 12 weeks after randomization
Secondary outcomes:
measure: high sensitivity C-reactive protein (CRP), hepcidin, Free Light Chains (FLC), Interleukin (IL)-6, Interleukin (IL)-10
timeFrame: baseline, 4, 8 and 12 weeks
measure: Urea, Hepcidin, Free Light Chains, IL-6, IL-10
timeFrame: baseline, week 1
measure: Albumin
timeFrame: baseline, weeks 2,4,6,8,10,12,14,16,18,20,22,24
Other outcomes:
Locations:
city: Bollate
country: Italy
facility: Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi
state: Milan
Study officials:
affiliation: Azienda Ospedaliera Garbagnate Milanese Ospedale Bollate - Divisione Nefrologia e Dialisi
name: Ugo Teatini, Dr.
role: PRINCIPAL_INVESTIGATOR
References: