Mid-HDF Randomized Controlled Study on Outcome

Not Applicable

• Conditions: End Stage Renal Disease
• Interventions: Device: HF dialysis; Device: Mid-dilution HDF

• Registration Number: NCT01693354
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-09-06
• Study First Submitted QC: 2012-09-24
• Study First Posted: 2012-09-26
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-12
• Last Update Posted: 2017-01-13
• Primary Completion: 2017-09
• Study Completion: 2018-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HF dialysis	HF dialysis	HF (high-flux) dialysis is standard hemodialysis treatment performed by using a high permeability dialyzer instead of a low permeability one.
Mid-dilution HDF	Mid-dilution HDF	Mid-dilution is a newly developed hemodiafiltration therapy able to allow a simultaneous pre- and post-dilution infusion.

Primary Outcome Measures

Name	Time	Method
crude, all-causes mortality	5 years	The primary objective will be assessed by the incidence rate of fatal events

Secondary Outcome Measures

Name	Time	Method
Quality of life and dialysis tolerance evaluated by questionnaire	1 year	It will be assessed by taking into consideration: - Results of the SF-36 questionnaire given to the patients
Micro-inflammation evaluation	1 year	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
Cardiovascular morbidity	5 years	It will be assessed by taking into consideration: * Number of hospital admissions related to non fatal major CV events; * Length of stay during hospitalization
Nutrition and anaemia management	1 year	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.

Trial Locations

Locations (4)

Hospital Clínic Barcelona; 🇪🇸 Barcelona, Spain

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Azienda Ospedaliero-Universitaria di Bologna; 🇮🇹 Bologna, Italy

Hôpital de la Conception; 🇫🇷 Marseille, France