Mid-HDF Randomized Controlled Study on Outcome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether mid-dilution hemodiafiltration is effective in the reduction of the crude mortality risk in patients who have been undergoing renal replacement treatment for less than 1 year. Patients will be randomized since the beginning of the study in two groups: standard HF dialysis and mid-dilution HDF.

Detailed Description
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It is a matter of fact that in the last decades the Chronic Kidney Disease (CKD) population has widely changed. In Italy, for example, more than 50% of the incident dialysis patients are more than 70 year old, with diabetic and hypertension being the major underlying diseases; moreover a great percentage of the patients starts dialysis with a burden of at least 1-2 comorbidities [1]. Online hemodiafiltration (online HDF) has been recently associated with better patient survival in comparison with standard hemodialysis in two large trials [2,3]; the overall relative risk of mortality was found to be approximately 33% lower in patients treated with online HDF [2,3]. These impressive results were not obtained anyway on the whole population, but in a sub-group analysis. A strong correlation was found between the total convective volume obtained and the mortality risk reduction; HDF was found to be significantly better than standard hemodialysis when a total convective volume of 19-22 L/session (in 4 hours sessions of post-dilution HDF) was achieved. These results support the importance of the adequate convective dose concept in order to improve the patient outcomes especially in frail patients, as recently demonstrated by a large randomised control trial, the MPO study [4], comparing High Flux versus Low Flux dialysis in patients with plasma albumin levels equal to or less than 4 gr/dl ( as a marker of patient comorbidities) and, in a post hoc analysis, in diabetic patients [4]. Mid-dilution HDF is a variant of classical HDF combining simultaneous pre- and post.-dilution in order to maximise middle and large solutes removal. The MILESTONE study would aim to fully demonstrate for mid-dilution HDF the significant mortality risk reduction observed in the recent mentioned studies.

Official Title
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Mid-dilution Hemodiafiltration International Randomized Prospective Study on Incident Patients Focused on Outcome

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: Mid-dilution HDF
* Device: HF dialysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On a thrice/week RRT for at least 3 months Dialysis vintage > 3 months Signed informed consent Blood flow > 300 mL/min Exclusion Criteria: On waiting list for living-donor transplant Residual diuresis > 500 mL/day Inability, as judget by the investigator, to follow or understand the protocol instructions Active neoplastic disease Single needle treatment Patients with expectancy life lower than 6 months Inclusion to other studies Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HF dialysis<br>HF (high-flux) dialysis is standard hemodialysis treatment performed by using a high permeability dialyzer instead of a low permeability one. | Device: HF dialysis<br>* Standard hemodialyzers equipped with high permeability polyphenylene/polyethersulfone membranes<br>* Other names: DIAPES HF;|
| Experimental: Mid-dilution HDF<br>Mid-dilution is a newly developed hemodiafiltration therapy able to allow a simultaneous pre- and post-dilution infusion. | Device: Mid-dilution HDF<br>* Mid-dilution HDF is a special, newly developed variant of online HDF which is characterized by a dedicated high-flux hemodialyzer named OLPUR MD able to support simultaneous pre- and post-dilution<br>* Other names: OLPUR MD 190;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| crude, all-causes mortality | The primary objective will be assessed by the incidence rate of fatal events | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular morbidity | It will be assessed by taking into consideration: Number of hospital admissions related to non fatal major CV events Length of stay during hospitalization | 5 years | 
| Quality of life and dialysis tolerance evaluated by questionnaire | It will be assessed by taking into consideration: - Results of the SF-36 questionnaire given to the patients | 1 year | 
| Micro-inflammation evaluation | It will be assessed by measuring the pre-dialysis serum levels of: IL-6 CR Myoglobin RbP p-cresylsulfate beta2-microglobulin. The hospitals' laboratories will be in charge for the sample collection and analysis | 1 year | 
| Nutrition and anaemia management | It will be assessed by taking in consideration the pre-dialysis serum levels of: Hb albumin iron. ESAs and iron supplementation will be as well noted in apposite CRF. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dialysis, mortality, cardiovascular stability, inflammation, quality of life