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Trial registered on ANZCTR


Registration number
ACTRN12616000905460
Ethics application status
Approved
Date submitted
5/07/2016
Date registered
8/07/2016
Date last updated
8/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Mixed dilution haemodiafiltration versus post dilution haemodiafiltration in adults with end stage kidney disease: a prospective randomised crossover trial
Scientific title
Mixed dilution haemodiafiltration versus post dilution haemodiafiltration in adults with end stage kidney disease: a prospective randomised crossover trial
Secondary ID [1] 289623 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemodiafiltration 299407 0
End stage kidney disease 299408 0
Condition category
Condition code
Renal and Urogenital 299388 299388 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Mixed dilution haemodiafiltration (HDF) is the intervention in this trial and post-dilution HDF is the control. Currently, dialysis patients are routinely managed with post-dilution HDF in the units in this study (which is consistent with other units who perform HDF in Australia and New Zealand). HDF involves large volumes of fluid convection (the primary mechanism of solute clearance) and, subsequently, large volumes of replacement fluid reinfusion. In post-dilution HDF, replacement fluid is reinfused after the dialysis membrane. In mixed-dilution HDF, replacement fluid is reinfused both before and after the dialysis membrane in a ratio that will allow the most efficient clearance of solutes while maintaining a safe transmembrane pressure (TMP, the pressure between the dialysis fluid and blood compartments). The ratio is controlled automatically by the dialysis machine to maintain TMP between 250 - 300 mmHg. Apart from the site of fluid replacement, no other dialysis parameters will differ from standard care (ie post-dilution HDF)

After screening, patients will be randomised 1:1 to arm A (mixed then post dilution HDF) or arm B (post dilution then mixed HDF). Following a 2 week run in period of post-dilution HDF, patients will commence the first of two 4 week intervention periods. These intervention periods will be separated by a 2 week washout period of post-dilution HDF.

In the intervention periods, patients will continue on their pre-trial dialysis session duration, treatment location and dialysis schedule (Monday/Wednesday/Friday or Tuesday/Thursday/Saturday). Dialysate composition will remain constant. Each session, convection volume, circuit clotting and peak transmembrane pressure will be recorded by dialysis nursing staff. In the final week of each intervention period, pre and post dialysis bloods (solute clearance, albumin and clotting) and a post-dialysis recovery time questionnaire will be performed.
Intervention code [1] 295236 0
Treatment: Other
Comparator / control treatment
Each patient will serve as their own control in this randomised crossover design. Post-dilution HDF is the control as this is currently the standard practice in the study dialysis units. Patients will continue their standard dialysis location, hours, prescription and dialysate composition
Control group
Active

Outcomes
Primary outcome [1] 298854 0
Convection volume
-this will be recorded each dialysis session during the intervention periods
-this figure is automatically reported by the dialysis machine
-this figure will be recorded in each patient's record by dialysis nursing staff
Timepoint [1] 298854 0
Week 4 of intervention periods 1 and 2
Secondary outcome [1] 325453 0
Solute clearance
-levels of small (urea), medium (B2 microglobulin), and large (retinol binding protein, cystatin C) solutes will be measured on blood samples taken before and after dialysis
-samples will be taken in the mid-week session
-solute clearance will be reported as a reduction ratio e.g. urea reduction ratio = (pre dialysis urea - post dialysis urea) / pre dialysis urea. This calculation will be performed for each of the 4 measured solutes
Timepoint [1] 325453 0
Week 4 of intervention periods 1 and 2
Secondary outcome [2] 325471 0
Peak transmembrane pressure
-measured automatically by dialysis machine each session
-recorded in patient file by dialysis nursing staff
Timepoint [2] 325471 0
Week 4 of intervention periods 1 and 2
Secondary outcome [3] 325472 0
Post dialysis recovery time
-survey of time taken for patients to recover following dialysis (0hr, 0-2hr, 2-6hr, 5-12hr, >12hr)
-recorded by patients and entered into patient file by dialysis nursing staff
Timepoint [3] 325472 0
Week 4 of intervention periods 1 and 2
Secondary outcome [4] 325473 0
CIrcuit clotting
-scale from 0 to 4 according to EDTNA ERCA audit to evaluate clotting in dialysis circuit
-recorded by nursing staff each session
Timepoint [4] 325473 0
Week 4 of intervention periods 1 and 2

Eligibility
Key inclusion criteria
Patients with end stage kidney disease on conventional in-centre haemodialysis with dialysis session duration 4-6hr, three times per week
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Incident haemodialysis patients (<3 months),
Temporary vascular access (HD central venous catheter)
Life expectancy <6 months
Medical instability –altered response criteria (airway, breathing, circulation, neurology)
Blood flow rate (Qb) <250mls/min
Non-adherence to prescribed treatment hours
Unable to tolerate post-dilution HDF
Residual urine output >500ml/day

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 294004 0
Hospital
Name [1] 294004 0
Princess Alexandra Hospital
Address [1] 294004 0
Level 2, Ambulatory Renal and Transplant Services Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country [1] 294004 0
Australia
Funding source category [2] 294008 0
Hospital
Name [2] 294008 0
Bundaberg Hospital
Address [2] 294008 0
Bundaberg Renal Unit
271 Bourbong St, Bundaberg, QLD 4670
Country [2] 294008 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
Level 2, Ambulatory Renal and Transplant Services Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 292823 0
Hospital
Name [1] 292823 0
Bundaberg Hospital
Address [1] 292823 0
Bundaberg Renal Unit
271 Bourbong St, Bundaberg, QLD 4670
Country [1] 292823 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295415 0
Princess Alexandra Hospital
Ethics committee address [1] 295415 0
Level 2, Ambulatory Renal and Transplant Services Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Ethics committee country [1] 295415 0
Australia
Date submitted for ethics approval [1] 295415 0
15/07/2016
Approval date [1] 295415 0
20/09/2016
Ethics approval number [1] 295415 0
HREC/16/QPAH/253

Summary
Brief summary
End stage kidney disease is increasing in incidence and many patients in Australia and New Zealand require renal replacement therapy. In 2014, 9147 patients were managed with haemodialysis (HD), and an additional 2207 patients were on haemodiafiltration (HDF) (ANZDATA 2016). Although the uptake of HDF relative to HD has increased considerably, HDF remains underutilized in Australia, especially when compared to uptake in Europe and some parts of Asia. HD performs solute clearance and volume removal by the process of diffusion, with minimal contribution from convection. HDF enhances small and middle molecule clearance through convection and diffusion, which may theoretically improve patient-level clinical outcomes. The safety of HDF has been confirmed by recently published meta-analysis.

Solute clearance by convection requires substantial volumes of ultrafiltration, which in turn necessitates the administration of exogenous fluid replacement. This fluid has traditionally been reinfused either before (pre-dilution HDF) or after (post-dilution HDF) the dialyser. Post-dilution HDF is highly efficient in terms of solute clearance, but concerns have been raised regarding haemoconcentration with an increase in theoretical risk of clotting. Pre-dilution HDF minimizes the risk of haemoconcentration but provides less efficient solute removal. In recent years, two novel HDF techniques (mixed- and mid-dilution HDF) have been developed, which permit simultaneous pre- and post-dilution delivery. Mixed-dilution HDF appears to offer the most optimal balance between solute clearance efficiency and haemoconcentration compared to other forms of HDF. However, its uptake has been limited in Australia in spite of its availability.

Few studies have assessed the clinical efficacy of mixed dilution HDF. Existing literature is limited by small patient numbers and limited outcome measures. This randomised crossover trial will compare convection volume, clotting, small/middle/large molecule clearance, circuit clotting and post dialysis recovery time between mixed and post dilution HDF
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67222 0
Ms Angela Henson
Address 67222 0
Level 2, Ambulatory Renal and Transplant Services Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country 67222 0
Australia
Phone 67222 0
+61731761111
Fax 67222 0
Email 67222 0
angela.henson@health.qld.gov.au
Contact person for public queries
Name 67223 0
Dr Emily See
Address 67223 0
Level 2, Ambulatory Renal and Transplant Services Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country 67223 0
Australia
Phone 67223 0
+61731761111
Fax 67223 0
Email 67223 0
emily.see@health.qld.gov.au
Contact person for scientific queries
Name 67224 0
Dr Emily See
Address 67224 0
Level 2, Ambulatory Renal and Transplant Services Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country 67224 0
Australia
Phone 67224 0
+61731761111
Fax 67224 0
Email 67224 0
emily.see@health.qld.gov.au

No information has been provided regarding IPD availability
Summary results
No Results