Mid-HDF Randomized Controlled Study on Outcome (MILESTONE)

This study is not yet open for participant recruitment. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 18, 2014