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

September 23, 2020 updated by: Simeone Andrulli, MD, A. Manzoni Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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:

  1. Biocompatibility of the previous membrane (categorical), iron status (transferrin saturation and ferritin), nutrition (albumin), intact PTH, inflammation (high- sensitivity C reactive protein);
  2. 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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. One of the following condition in the last 3 months :

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
every other month

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

A. Manzoni Hospital

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

March 1, 2007

Study Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

May 6, 2008

First Submitted That Met QC Criteria

May 29, 2008

First Posted (Estimate)

May 30, 2008

Study Record Updates

Last Update Posted (Actual)

September 25, 2020

Last Update Submitted That Met QC Criteria

September 23, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Vit E-Rif01-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Anemia

Clinical Trials on VitabranE ViE

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Netherlands

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe