Clinical trial NCT01693354: Mid-HDF Randomized Controlled Study on Outcome
Official title: Mid-dilution Hemodiafiltration International Randomized Prospective Study on Incident Patients Focused on Outcome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: End Stage Renal Disease
Keywords: dialysis
mortality
cardiovascular stability
inflammation
quality of life
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2012-09-26
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: crude, all-causes mortality
timeFrame: 5 years
Secondary outcomes:
measure: Cardiovascular morbidity
timeFrame: 5 years
measure: Quality of life and dialysis tolerance evaluated by questionnaire
timeFrame: 1 year
measure: Micro-inflammation evaluation
timeFrame: 1 year
measure: Nutrition and anaemia management
timeFrame: 1 year
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Marseille
country: France
facility: Hôpital de la Conception
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna
city: Barcelona
country: Spain
facility: Hospital Clínic Barcelona
Study officials:
affiliation: Hospital Clínic Barcelona, Spain
name: Francisco Maduell, MD
role: STUDY_CHAIR
affiliation: AUSL 12 Viareggio, Italy
name: Vincenzo Panichi, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Reina Sofia, Cordoba, Spain
name: Pedro Aljama, MD, PhD
role: STUDY_CHAIR
affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium
name: Michel Jadoul, MD, PhD
role: STUDY_CHAIR
affiliation: Hôpital de la Conception, Marseille, France
name: Philippe Brunet, MD, PhD
role: STUDY_CHAIR
affiliation: AOSP Bologna, Italy
name: Antonio Santoro, MD
role: STUDY_CHAIR
References:
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 precis. NDT Plus. 2011 Feb;4(1):1-13. doi: 10.1093/ndtplus/sfq191. Epub 2010 Nov 19.
citation: Grooteman MP, van den Dorpel MA, Bots ML, Penne EL, van der Weerd NC, Mazairac AH, den Hoedt CH, van der Tweel I, Levesque R, Nube 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. Epub 2012 Apr 26.
citation: 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. doi: 10.1038/sj.ki.5000447.
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. Epub 2008 Dec 17.