Mid-HDF Randomized Controlled Study on Outcome

End Stage Renal Disease Clinical Trial

— MILESTONE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01693354
• Other study ID #: MID-INT01
• Status: Active, not recruiting
• Phase: N/A
• First received: September 6, 2012
• Last updated: January 12, 2017
• Start date: September 2012
• Est. completion date: September 2018

Study information

• Verified date: January 2017
• Source: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: September 2018
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

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
• HF dialysis
Standard hemodialyzers equipped with high permeability polyphenylene/polyethersulfone membranes

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
France	Hôpital de la Conception	Marseille
Italy	Azienda Ospedaliero-Universitaria di Bologna	Bologna
Spain	Hospital Clínic Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

Countries where clinical trial is conducted

Belgium,  France,  Italy,  Spain, 

References & Publications (4)

Canaud B, Bragg-Gresham JL, Marshall MR, Desmeules S, Gillespie BW, Depner T, Klassen P, Port FK. Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS. Kidney Int. 2006 Jun;69(11):2087-93. — View Citation

Grooteman MP, van den Dorpel MA, Bots ML, Penne EL, van der Weerd NC, Mazairac AH, den Hoedt CH, van der Tweel I, Lévesque R, Nubé MJ, ter Wee PM, Blankestijn PJ; CONTRAST Investigators.. Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes. J Am Soc Nephrol. 2012 Jun;23(6):1087-96. doi: 10.1681/ASN.2011121140. — View Citation

Locatelli F, Martin-Malo A, Hannedouche T, Loureiro A, Papadimitriou M, Wizemann V, Jacobson SH, Czekalski S, Ronco C, Vanholder R; Membrane Permeability Outcome (MPO) Study Group.. Effect of membrane permeability on survival of hemodialysis patients. J Am Soc Nephrol. 2009 Mar;20(3):645-54. doi: 10.1681/ASN.2008060590. — View Citation

Stel VS, van de Luijtgaarden MW, Wanner C, Jager KJ; on behalf of the European Renal Registry Investigators.. The 2008 ERA-EDTA Registry Annual Report-a précis. NDT Plus. 2011 Feb;4(1):1-13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	crude, all-causes mortality	The primary objective will be assessed by the incidence rate of fatal events	5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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