Ignite Creation Date:
2025-12-25 @ 12:26 AM
Ignite Modification Date:
2025-12-25 @ 10:32 PM
Study NCT ID:
NCT00687258
Status:
COMPLETED
Last Update Posted:
2020-09-25
First Post:
2008-05-06
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Evaluation Of A New Vitamin E-Bonded Membrane On Anemia And Oxidative Stress In End-Stage Renal Disease Patients
Sponsor:
A. Manzoni Hospital
Organization:
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2020-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Vi-E
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.
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.
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: