Evaluation Of A New Vitamin E-Bonded Membrane On Anemia And Oxidative Stress In End-Stage Renal Disease Patients (Vi-E)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00687258

Recruitment Status : Completed

First Posted : May 30, 2008

Last Update Posted : September 25, 2020

Sponsor:

Information provided by (Responsible Party):

Simeone Andrulli, MD, A. Manzoni Hospital

Study Description

Brief Summary:

The main purpose of this longitudinal study is to point out the effect of VitabranE on the ESA resistance and on the anemia observed in HD patients undergoing EPO maintenance therapy.

As a secondary purpose we will consider the effect of VitabranE on inflammation and oxidative stress parameters as a function of the changes observed in the anemia parameters.

Condition or disease	Intervention/treatment	Phase
Anemia	Device: VitabranE ViE	Phase 2

Show detailed description

Detailed Description:

Aim

The aim of this pilot randomized study is to verify whether the addition of vitamin E alpha-tocopherol to the blood-side layer of a synthetic polysulfone dialyser membrane has a clinical advantage in terms of ESA responsiveness and, consequently, the anemic status of hemodialysed patients.

Patients

Patients of both genders aged more than 18 years will be considered eligible for the study if they had been receiving bicarbonate hemodialysis treatment for at least six months and stable ESA therapy for at least three months, and had adequate iron stores (ferritin levels >200 ng/ml and transferrin saturation >20%). Patients with haemoglobinopathies, sickle cell anemia, thalassemia or malignancies will be excluded, as were those who had experienced infection, vascular access thrombosis, stroke, myocardial infarction, heavy blood loss, major surgery or blood transfusion in the previous three months.

Study design

This is an 8-month, controlled and randomised study of two parallel groups; after giving their informed consent, the enrolled patients will be randomly assigned to the Vi-E experimental treatment (polysulfone dialyser with vitamin E alpha-tocopherol) or the PS control treatment (polysulfone dialyser without vitamin E alpha-tocopherol).

Clinical data

The dialyser will be randomly assigned at the beginning of the study, and pre and end-dialysis body weight, blood pressure and heart rate will be recorded at baseline and every two months. Dialysis prescription will not change during the study. All of the drugs administered during each dialysis session will be recorded, as all of the prescribed inter-dialysis therapies.

Laboratory data

Hemoglobin, serum albumin and plasma high-sensitivity C reactive protein levels (ELISA) will be recorded at baseline and every other month, together with nutritional and inflammation indices. Iron status will be evaluated on the basis of transferrin saturation and plasma ferritin levels. Reticulocytes and PTH levels will be also recorded. Equilibrated Kt/V will be calculated in order to estimate the dialysis dose of low molecular weight uraemic toxins, and the appearance of urea nitrogen will be calculated in order to estimate daily protein intake.

Plasma alpha-tocopherol and gamma tocopherol levels will be determined by means of reverse-phase HPLC analysis; total antioxidant capacity (TAC) will be determined using the ferric reducing-antioxidant power and advanced glycation end-products will be detected using total fluorescence at 335/385 Ex/Em. Advanced oxidation protein products, carbonyl products, erythrocyte creatine and interleukin 6 will be also determined.

Main response variable

The primary outcome measure will be the ESA resistance index, a combined variable calculated by dividing the weekly ESA dose by haemoglobin level and end-dialysis body weight.

Sample size

Given the pilot nature of the study, it is estimated that a sample of twenty patients (ten patients per group) will be sufficient to provide reasonable control over random variations in ESA resistance.

Statistical analysis

The data will be described using median values and interquartile ranges based on 25th and 75th percentiles for the distributed continuous variables. The baseline distribution of the continuous and categorical variables by group will be investigated using the Mann-Whitney and Chi-squared tests as appropriate.

The follow-up data will be analyzed using analysis of variance for repeated measures in order to test the possible differences in ESA resistance over time between the two groups.

A secondary analysis will be made by adding the values of some baseline covariates in order to identify predictors associated with ESA resistance. In order to reduce over-parameterizing the model, the explored covariates will be grouped in two hierarchical steps:

Biocompatibility of the previous membrane (categorical), iron status (transferrin saturation and ferritin), nutrition (albumin), intact PTH, inflammation (high- sensitivity C reactive protein);
Add some markers of oxidative stress (TAC, alpha- and gamma-TOC, carbonyl products, AOPP, AGEs and erythrocyte creatine) The effect of the experimental treatment over time will be tested by means of group interaction, with this hierarchical approach.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Evaluation Of The Impact Of A New Synthetic Vitamin E-Bonded Membrane On The Anemia And Oxidative Stress In End-Stage Renal Disease (ESRD) Patients
Study Start Date :	July 2006
Actual Primary Completion Date :	March 2007
Actual Study Completion Date :	July 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Kidney Failure Vitamin E

Drug Information available for: alpha-Tocopherol Vitamin E Tocopherol alpha-Tocopherol succinate Tocopherol acetate DL-alpha-Tocopherol

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 VitabranE ViE: Vitamin E-bonded polysulfone dialyzer	Device: VitabranE ViE Polysulfone dialyser with vitamin E alpha-tocopherol Other Name: Vitamin E-bonded polysulfone dialyzer
No Intervention: 2 APS-U (Asahi Polysulfone APS): Polysulfone dialyzer

Outcome Measures

Primary Outcome Measures :

The primary outcome measure will be the ESA resistance index, a combined variable calculated by dividing the weekly ESA dose by haemoglobin level and end-dialysis body weight. [ Time Frame: every other month ]

Secondary Outcome Measures :

Inflammatory status (CRP and IL-6) and oxidative stress markers (Vitamin E levels, TAC, Protein carbonyls and AOPP, AGEs). [ Time Frame: every other month ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female patients, aged ≥ 18, stabilized on BHD for at least 6 months.
Clinical stability during the last 3 months.
Serum Ferritin > 200 mg/L and Transferrin saturation >30%.
Maintenance therapy with epoetin alfa/beta or darbepoetin alfa.

Exclusion Criteria:

One of the following condition in the last 3 months :
- acute infection
- vascular access thrombosis
- ictus cerebri
- myocardial stroke
- haemorrhage
- major surgery
- haemo-transfusion
Haemoglobinopaty, sickle cell anemia, familial erythroblastic anemia and any other haematological disorder interfering with the aim of the study
Malignancy
Participation to other studies or use of EPO analogues not yet commercialized
pharmacological dosage administration of antioxidant supplements

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00687258

Locations

Layout table for location information

Italy
Alessandro Manzoni Hospital, Nephrology and Dialysis Department
Lecco, Italy, 23900

Sponsors and Collaborators

A. Manzoni Hospital

Investigators

Layout table for investigator information

Principal Investigator:	Francesco Locatelli, MD	Nephrology and Dialysis Department - A. Manzoni Hospital

More Information

Publications of Results:

Andrulli S, Di Filippo S, Manzoni C, Stefanelli L, Floridi A, Galli F, Locatelli F. Effect of synthetic vitamin E-bonded membrane on responsiveness to erythropoiesis-stimulating agents in hemodialysis patients: a pilot study. Nephron Clin Pract. 2010;115(1):c82-9. doi: 10.1159/000294281. Epub 2010 Mar 8.

Layout table for additonal information

Responsible Party:	Simeone Andrulli, MD, A. Manzoni Hospital
ClinicalTrials.gov Identifier:	NCT00687258
Other Study ID Numbers:	Vit E-Rif01-1
First Posted:	May 30, 2008 Key Record Dates
Last Update Posted:	September 25, 2020
Last Verified:	September 2020

Keywords provided by Simeone Andrulli, MD, A. Manzoni Hospital:


Anemia Oxidative Stress Erythropoietin dialyser membrane	Vitamin E Erythropoietin responsiveness Erythropoietin resistance hemodialysis

Additional relevant MeSH terms:

Layout table for MeSH terms

Kidney Failure, Chronic Anemia Hematologic Diseases Kidney Diseases Urologic Diseases Renal Insufficiency, Chronic Renal Insufficiency	Vitamin E Vitamins Micronutrients Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents

To Top