Mid-HDF Randomized Controlled Study on Outcome (MILESTONE)

This study is not yet open for participant recruitment.
Verified September 2012 by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Sponsor:
Information provided by (Responsible Party):
Antonio Santoro, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov Identifier:
NCT01693354
First received: September 6, 2012
Last updated: September 24, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention
End Stage Renal Disease
Device: Mid-dilution HDF
Device: HF dialysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mid-dilution Hemodiafiltration International Randomized Prospective Study on Incident Patients Focused on Outcome

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:

Primary Outcome Measures:
  • crude, all-causes mortality [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The primary objective will be assessed by the incidence rate of fatal events


Secondary Outcome Measures:
  • Cardiovascular morbidity [ Time Frame: 5 years ] [ Designated as safety issue: No ]

    It will be assessed by taking into consideration:

    • Number of hospital admissions related to non fatal major CV events
    • Length of stay during hospitalization

  • Quality of life and dialysis tolerance evaluated by questionnaire [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    It will be assessed by taking into consideration:

    - Results of the SF-36 questionnaire given to the patients


  • Micro-inflammation evaluation [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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


  • Nutrition and anaemia management [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 800
Study Start Date: September 2012
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: HF dialysis
HF (high-flux) dialysis is standard hemodialysis treatment performed by using a high permeability dialyzer instead of a low permeability one.
Device: HF dialysis
Standard hemodialyzers equipped with high permeability polyphenylene/polyethersulfone membranes
Other Names:
  • PHYLTHER HF
  • DIAPES HF
Experimental: Mid-dilution HDF
Mid-dilution is a newly developed hemodiafiltration therapy able to allow a simultaneous pre- and post-dilution infusion.
Device: Mid-dilution HDF
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
Other Names:
  • OLPUR MD 220
  • OLPUR MD 190

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • On a thrice/week RRT for at least 3 months
  • Dialysis vintage less than 6 months
  • Signed informed consent
  • Blood flow > 300 mL/min

Exclusion Criteria:

  • In list for transplant within the next two years
  • Active neoplastic disease
  • Mental illness
  • History of major cardiovascular events within six months prior to the study
  • Single needle treatment
  • Life expectancy life less than 1 year
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01693354

Contacts
Contact: Antonio Santoro, MD (+39)0516362430 antonio.santoro@aosp.bo.it

Locations
Belgium
Cliniques Universitaires Saint-Luc Not yet recruiting
Brussels, Belgium, 3000
Contact: Michel Jadoul, MD, PhD    (+32) 02 764 18 55    michel.jadoul@uclouvain.be   
Principal Investigator: Michel Jadoul, MD, PhD         
France
Hôpital de la Conception Not yet recruiting
Marseille, France, 13385
Contact: Philippe Brunet, MD, PhD    (+33) 4 91 383042    pbrunet@mail.ap-hm.fr   
Principal Investigator: Philippe Brunet, MD, PhD         
Italy
Azienda Ospedaliero-Universitaria di Bologna Not yet recruiting
Bologna, Italy, 40138
Contact: Elena Mancini, MD    (+39)0516362431    elena.mancini@aosp.bo.it   
Sub-Investigator: Elena Mancini, MD         
Principal Investigator: Antonio Santoro, MD         
Spain
Hospital Clínic Barcelona Not yet recruiting
Barcelona, Spain, 08036
Contact: Francisco Maduell, MD    (+34) 93 227 93 46    fmaduell@clinic.ub.es   
Principal Investigator: Francisco Maduell, MD         
Sponsors and Collaborators
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Investigators
Study Chair: Francisco Maduell, MD Hospital Clínic Barcelona, Spain
Study Chair: Vincenzo Panichi, MD, PhD AUSL 12 Viareggio, Italy
Study Chair: Pedro Aljama, MD, PhD Hospital Reina Sofia, Cordoba, Spain
Study Chair: Michel Jadoul, MD, PhD Cliniques Universitaires Saint-Luc, Brussels, Belgium
Study Chair: Philippe Brunet, MD, PhD Hôpital de la Conception, Marseille, France
Study Chair: Antonio Santoro, MD AOSP Bologna, Italy
  More Information

Publications:
Responsible Party: Antonio Santoro, Professor Antonio Santoro MD, Chief of Nephrology, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov Identifier: NCT01693354     History of Changes
Other Study ID Numbers: MID-INT01
Study First Received: September 6, 2012
Last Updated: September 24, 2012
Health Authority: Italy: National Institute of Health

Keywords provided by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:
dialysis
mortality
cardiovascular stability
inflammation
quality of life

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on April 15, 2014