Effect of an eXtended Permeability DiAlysis MembraNe on ESA Resistance in HemoDialysis Patients
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 110
- 主要终点
- Change of the "Erythropoietin Responsiveness factor" (EPO index)
研究概览
简要总结
It is hypothesized that a consistent use of Medium cut-off membrane (Theranova) increased clearance of pro-inflammatory molecules in a broad molecular weight range attenuates the chronic inflammatory state in patients with poor response to ESA therapy and absence of absolute iron deficiency and that this leads to an improvement in ESA responsiveness (EPO resistance index).
详细描述
Hemodialysis Patients present chronic inflammation caused by multiple inflammatory stimuli. Chronic inflammation is linked to clinical signs and symptoms and cardiovascular mortality in these patients. Inflamed dialysis patients show impaired response to erythropoiesis-stimulating agents (ESA) mainly related to a reduced iron utilization (functional iron deficiency) 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 Theranova Medium cut-off membrane allows for significant clearance of medium molecular toxins and we know that a number of uremic solutes have been identified as pro-inflammatory, including several with a molecular weight in the size range of 20-45 kDa (cytokines, kappa/lambda free light chains and hepcidine). The EPO index has been previously used in clinical trials to measure EPO responsiveness [2,3] and is associated with mortality of ESRD patients [4-7].
All AE, SAE and other safety issues will be collected and described. The even review committee could be consulted in case of Safety event, and give recommendations.
Data entry to be carried out into an electronic CRF hosted database. This database allows the follow-up of any modifications made during data entry and monitoring. Data consistency will be checked on line according to the procedure described in the Data Management Plan (DMP), as part of the Study Master File. Each eCRF follows the study schedule structure. It is divided in sections for each visits or specific forms.
Eligible patients will be consecutively randomized in a 1:1 fashion to the standard dialysis or to dialysis with MCO dialyzer. The random sequence will be centrally generated in the CRF tool. The randomization procedure will be stratified per centre. Size of block is only known by the statistician to keep the investigator blinded regarding group allocation for the next patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ESRD treated with chronic HD for at least 3 months
- •Treatment with high flux dialyzers for at least 3 months
- •Age ≥18 years
- •Receiving intravenous short acting 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)
- •Signed informed consent.
排除标准
- •Acute infection ≤4 weeks prior to randomization
- •HIV or hepatitis infection
- •Central Venous Catheter (with the history of infections in the latest 3 months)
- •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
- •Inability to give informed consent.
研究组 & 干预措施
Control group
Conventional Hemodialysis using a high-flux dialyzer
干预措施: High-flux dialyzer (Device)
Experimental group
Conventional Hemodialysis using a medium cut-of dialyzer
干预措施: Medium cut-off dialyzer (Device)
结局指标
主要结局
Change of the "Erythropoietin Responsiveness factor" (EPO index)
时间窗: Up to 48 weeks
EPO index will be calculated as the average weekly EPO dose in IU per kg BW in the preceding 4 weeks divided by the last measured Hb
次要结局
- Inflammation status(Up to 48 weeks)
- Metabolic diseases(Up to 48 weeks)
研究者
Carlo Maria Guastoni
Head of Operative Unit of Dialysis and Nephrology
Azienda Ospedaliera, Ospedale Civile di Legnano