Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000804482
Ethics application status
Approved
Date submitted
8/06/2016
Date registered
21/06/2016
Date last updated
30/06/2021
Date data sharing statement initially provided
30/06/2021
Date results information initially provided
30/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A single arm, non-randomised device trial to assess the effect of the Theranova Dialyser on albumin and uraemic solutes in patients with Stage V chronic kidney disease requiring haemodialysis
Scientific title
A single arm, non-randomised device trial to assess the effect of the Theranova Dialyser on albumin and uraemic solutes in patients with Stage V chronic kidney disease requiring haemodialysis
Secondary ID [1] 289254 0
None
Universal Trial Number (UTN)
Trial acronym
REMOVAL-HD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End Stage Kidney Disease 298830 0
Condition category
Condition code
Renal and Urogenital 298891 298891 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive six months’ treatment with the Theranova dialyzer three times per week. Theranova, the Baxter Mid Cut-Off dialyzer has a pore size of 7 nm but narrower distribution of pores compared to high cut-off membrane. It has been designed to provide increased clearance of these larger middle-molecules in chronic haemodialysis patients, compared with high flux HD (the standard HD treatment method).

Prior to intervention, participants will also receive a one-month wash-in and one month wash out period after treatment period using the Revaclear high-flux membrane.

Although all dialysis prescriptions will remain under the supervision of the local nephrology team (thus prescriptions may vary based on local and individual patient requirements), the following treatment guidance is provided:
- target blood flow >300mls/min,
- dialysate flow rate 500mls/min,
- fluid removal to participant’s individual prescription

All participants are in-centre patients and will be withdrawn from treatment if participant transfers to another renal unit which is not an active study site
Intervention code [1] 294798 0
Treatment: Devices
Comparator / control treatment
No control treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298361 0
Percentage change in pre-dialysis concentrations of centrally tested serum albumin
Timepoint [1] 298361 0
At baseline and 6 months
Secondary outcome [1] 323936 0
Proportion of population with a drop in serum albumin of >5% from baseline value
Timepoint [1] 323936 0
All visits between baseline and 6 months
Secondary outcome [2] 323937 0
Changes in centrally collected serum B2-microglobulin levels
Timepoint [2] 323937 0
At Baseline, 3 and 6 months
Secondary outcome [3] 323938 0
Number of all-cause hospitalization as reported by sites
Timepoint [3] 323938 0
Between baseline and 6 months
Secondary outcome [4] 323939 0
Number of hospitalizations related to infections as rated by site staff
Timepoint [4] 323939 0
Between baseline and 6 months
Secondary outcome [5] 324600 0
Change in restless leg symptoms using the Restless Legs Syndrome Rating Scale
Timepoint [5] 324600 0
At baseline, 3 and 6 months
Secondary outcome [6] 324601 0
Functional status with 6 minute walk test–the distance a participant can achieve by walking on a flat surface in 6 minutes is measured using trundle wheel
Timepoint [6] 324601 0
At baseline, 3 and 6 months
Secondary outcome [7] 324602 0
Malnutrition Inflammation Score (MIS
Timepoint [7] 324602 0
At baseline, 3 and 6 months
Secondary outcome [8] 324603 0
Number of participants with erythropoietin resistance as measured via erythropoietin resistance index (ERI) in participants taking erythropoietin (ERI greater than or equal to 1.0 IU/kg/week/gHb) or darbepoetin (ERI greater than or equal to 0.005 mircog/kg/week/gHb)
Timepoint [8] 324603 0
Between baseline and 6 months
Secondary outcome [9] 324604 0
All-cause mortality
Timepoint [9] 324604 0
Over 6 months
Secondary outcome [10] 324642 0
Change in centrally collection serum lambda/kappa free light chains levels

Timepoint [10] 324642 0
All visits between baseline and month 6
Secondary outcome [11] 324643 0
Change in centrally collected serum high sensitivity C-Reactive Protein (hsCRP)
Timepoint [11] 324643 0
At baseline, 3 and 6 months
Secondary outcome [12] 324644 0
Change in coagulation factors – INR/APTT
Timepoint [12] 324644 0
At baseline, 3 and 6 months
Secondary outcome [13] 324646 0
Duration of all-cause hospitalization as reported by sites
Timepoint [13] 324646 0
Between baseline and 6 months
Secondary outcome [14] 324647 0
Change in quality of life measured using Edmonton Symptom Assessment Scale
Timepoint [14] 324647 0
At baseline, 3 and 6 months

Eligibility
Key inclusion criteria
1. Established chronic in-centre HD patient (>12 weeks on HD)
2. Has a functioning Arterio Venous Fistula or Graft
3. Either oliguric (<500mls/24hrs based on 24hr urine collection within 12 weeks of screening) or anuric
4. Able to give informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Planned renal transplant within study intervention period
2. Planned conversion to peritoneal dialysis or transfer to another dialysis unit within study intervention period
3. Active chronic infection or significant active inflammatory conditions including autoimmune disease, inflammatory arthritis and active malignancy
4. Life expectancy <12 months
5. Pregnancy or breast feeding
6. Indication for HDF according to treating physician
7. Dialysis catheter in situ
8. Receiving immunosuppressant medication
9. Current use of nutritional or dietary supplements to increase or reduce protein intake including protein powder or weight loss supplements and is unable to cease the supplement
10. Serum albumin <30g/L (within 4 weeks of screening)
11. Inability to complete study assessments

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/09/2016
Actual
5/01/2017
Date of last participant enrolment
Anticipated
11/08/2017
Actual
7/09/2017
Date of last data collection
Anticipated
Actual
26/04/2018
Sample size
Target
85
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5818 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 5819 0
Nambour General Hospital - Nambour
Recruitment hospital [3] 5820 0
Concord Repatriation Hospital - Concord
Recruitment hospital [4] 7485 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [5] 7486 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [6] 7487 0
Epworth Eastern Hospital - Box Hill
Recruitment hospital [7] 7488 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [8] 7489 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 15308 0
2076 - Wahroonga
Recruitment postcode(s) [2] 13378 0
2139 - Concord Repatriation Hospital
Recruitment postcode(s) [3] 15312 0
3021 - St Albans
Recruitment postcode(s) [4] 15311 0
3050 - Parkville
Recruitment postcode(s) [5] 15309 0
3084 - Heidelberg
Recruitment postcode(s) [6] 15310 0
3128 - Box Hill
Recruitment postcode(s) [7] 13270 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 13271 0
4560 - Nambour
Recruitment outside Australia
Country [1] 7886 0
New Zealand
State/province [1] 7886 0

Funding & Sponsors
Funding source category [1] 293631 0
Commercial sector/Industry
Name [1] 293631 0
Baxter IIS grant
Country [1] 293631 0
United States of America
Primary sponsor type
University
Name
The University of Queensland
Address
Australasian Kidney Trial Network
Princess Alexandra Hospital
Building 1, Level 4
Ipswich Rd
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 292466 0
None
Name [1] 292466 0
none
Address [1] 292466 0
none
Country [1] 292466 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295209 0
Melbourne Health HREC
Ethics committee address [1] 295209 0
Level 2
South West
300 Grattan Street
Parkville 3050 Victoria
Ethics committee country [1] 295209 0
Australia
Date submitted for ethics approval [1] 295209 0
27/07/2016
Approval date [1] 295209 0
29/09/2016
Ethics approval number [1] 295209 0
HREC/16/MH/228
Ethics committee name [2] 295210 0
Northern B Health and Disability Ethics Committee
Ethics committee address [2] 295210 0
Ministry of Health C/- MEDSAFE Level 6 Deloitte House 10 Brandon Street PO Box 5013 Wellington NZ 6011
Ethics committee country [2] 295210 0
New Zealand
Date submitted for ethics approval [2] 295210 0
12/07/2016
Approval date [2] 295210 0
12/12/2016
Ethics approval number [2] 295210 0
16/NTB/126

Summary
Brief summary
Haemodialysis remains a principal renal replacement modality for patients with end stage renal disease (ESRD). Despite the efficacy of haemodialysis as a treatment to replace essential kidney functions, such as fluid and acid-base balance, the morbidity and mortality of patients receiving haemodialysis remains high when compared with the general population. Of many factors, the inadequate removal of some uraemic solutes might play a role in this phenomenon. Middle molecules are a well described class of uraemic solutes which have been linked to both the reduced quality of life and survival associated with end stage kidney disease. To date larger middle molecules have been inadequately removed by haemodialysis strategies. The mid cut-off dialyser Theranova represents a new class of dialysis membranes with the ability to remove nearly all middle molecules.

REMOVAL-HD is a pivotal, open label, non-randomized, single-arm, multi-center device study. The primary objective of the REMOVAL-HD study is to determine if regular haemodialysis using the Baxter Theranova dialyser in a chronic haemodialysis population can significantly decrease serum concentrations of large middle molecules without resulting in a significant loss of albumin. Participant will have 4 weeks wash-in period of high flux haemodialysis, then 26 weeks of treatment the mid cut-off dialyser Theranova and then 4 weeks wash-out with high flux haemodialysis. The primary study outcome is change in serum albumin at 6 months. Secondary outcomes include levels of uremic toxins over 6 months of treatment, the burden of HD related symptoms such as restless legs and general quality of life, functional measures of the 6-minute walk and rate of hospitalizations, infections and death.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65990 0
Dr Colin Hutchison
Address 65990 0
Hasting Memorial Hospital
398 Omahu Rd,
Camberley,
Hastings 4120,
Country 65990 0
New Zealand
Phone 65990 0
+64277035651
Fax 65990 0
Email 65990 0
Colin.Hutchison@hawkesbaydhb.govt.nz
Contact person for public queries
Name 65991 0
Ms Peta-Anne Paul-Brent
Address 65991 0
Australasian Kidney Trial Network
The university of Queensland
Princess Alexandra Hospital
Building 1, Level 4
Ipswich Rd
Woolloongabba QLD 4102
Country 65991 0
Australia
Phone 65991 0
+61 7 3176 5817
Fax 65991 0
Email 65991 0
removalhd@uq.edu.au
Contact person for scientific queries
Name 65992 0
Ms Peta-Anne Paul-Brent
Address 65992 0
Australasian Kidney Trial Network
The university of Queensland
Princess Alexandra Hospital
Building 1, Level 4
Ipswich Rd
Woolloongabba QLD 4102
Country 65992 0
Australia
Phone 65992 0
+61 7 3176 5817
Fax 65992 0
Email 65992 0
removalhd@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Statistical analysis plan https://aktn.org.au/wp-content/uploads/2020/04/REMOVAL_SAP_v2.0_Redacted.pdf 


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes A tRial Evaluating Mid Cut-Off Value Membrane Clea... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA trial evaluating mid cut-off value membrane clearance of albumin and light chains in hemodialysis patients: A safety device study.2020https://dx.doi.org/10.1159/000505567
EmbaseDesign and methods of the REMOVAL-HD study: A tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.2018https://dx.doi.org/10.1186/s12882-018-0883-8
N.B. These documents automatically identified may not have been verified by the study sponsor.