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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 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]

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

Condition category

Condition code

Renal and Urogenital

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All participants are in-centre patients and will be withdrawn from treatment if participant transfers to another renal unit which is not an active study site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]

Treatment: Devices

Comparator / control treatment

No control treatment

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Percentage change in pre-dialysis concentrations of centrally tested serum albumin

Timepoint [1]

At baseline and 6 months

Secondary outcome [1]

Proportion of population with a drop in serum albumin of >5% from baseline value

Timepoint [1]

All visits between baseline and 6 months

Secondary outcome [2]

Changes in centrally collected serum B2-microglobulin levels

Timepoint [2]

At Baseline, 3 and 6 months

Secondary outcome [3]

Number of all-cause hospitalization as reported by sites

Timepoint [3]

Between baseline and 6 months

Secondary outcome [4]

Number of hospitalizations related to infections as rated by site staff

Timepoint [4]

Between baseline and 6 months

Secondary outcome [5]

Change in restless leg symptoms using the Restless Legs Syndrome Rating Scale

Timepoint [5]

At baseline, 3 and 6 months

Secondary outcome [6]

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]

At baseline, 3 and 6 months

Secondary outcome [7]

Malnutrition Inflammation Score (MIS

Timepoint [7]

At baseline, 3 and 6 months

Secondary outcome [8]

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]

Between baseline and 6 months

Secondary outcome [9]

All-cause mortality

Timepoint [9]

Over 6 months

Secondary outcome [10]

Change in centrally collection serum lambda/kappa free light chains levels

Timepoint [10]

All visits between baseline and month 6

Secondary outcome [11]

Change in centrally collected serum high sensitivity C-Reactive Protein (hsCRP)

Timepoint [11]

At baseline, 3 and 6 months

Secondary outcome [12]

Change in coagulation factors – INR/APTT

Timepoint [12]

At baseline, 3 and 6 months

Secondary outcome [13]

Duration of all-cause hospitalization as reported by sites

Timepoint [13]

Between baseline and 6 months

Secondary outcome [14]

Change in quality of life measured using Edmonton Symptom Assessment Scale

Timepoint [14]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [2]

Nambour General Hospital - Nambour

Recruitment hospital [3]

Concord Repatriation Hospital - Concord

Recruitment hospital [4]

Sydney Adventist Hospital - Wahroonga

Recruitment hospital [5]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [6]

Epworth Eastern Hospital - Box Hill

Recruitment hospital [7]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [8]

Sunshine Hospital - St Albans

Recruitment postcode(s) [1]

4102 - Woolloongabba

Recruitment postcode(s) [2]

4560 - Nambour

Recruitment postcode(s) [3]

2139 - Concord Repatriation Hospital

Recruitment postcode(s) [4]

2076 - Wahroonga

Recruitment postcode(s) [5]

3084 - Heidelberg

Recruitment postcode(s) [6]

3128 - Box Hill

Recruitment postcode(s) [7]

3050 - Parkville

Recruitment postcode(s) [8]

3021 - St Albans

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Baxter IIS grant

Address [1]

Mailing address:
Baxter Healthcare Corporation
25212 W Il Route 120, RLT-10
Round Lake, IL 60073

Country [1]

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]

None

Name [1]

none

Address [1]

none

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC

Ethics committee address [1]

Level 2
South West
300 Grattan Street
Parkville 3050 Victoria

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/07/2016

Approval date [1]

29/09/2016

Ethics approval number [1]

HREC/16/MH/228

Ethics committee name [2]

Northern B Health and Disability Ethics Committee

Ethics committee address [2]

Ministry of Health C/- MEDSAFE Level 6 Deloitte House 10 Brandon Street PO Box 5013 Wellington NZ 6011

Ethics committee country [2]

New Zealand

Date submitted for ethics approval [2]

12/07/2016

Approval date [2]

12/12/2016

Ethics approval number [2]

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

Dr Colin Hutchison

Address

Hasting Memorial Hospital
398 Omahu Rd,
Camberley,
Hastings 4120,

Country

New Zealand

Phone

+64277035651

Fax

[email protected]

Contact person for public queries

Name

Peta-Anne Paul-Brent

Address

Australasian Kidney Trial Network
The university of Queensland
Princess Alexandra Hospital
Building 1, Level 4
Ipswich Rd
Woolloongabba QLD 4102

Country

Australia

Phone

+61 7 3176 5817

Fax

[email protected]

Contact person for scientific queries

Name

Peta-Anne Paul-Brent

Address

Australasian Kidney Trial Network
The university of Queensland
Princess Alexandra Hospital
Building 1, Level 4
Ipswich Rd
Woolloongabba QLD 4102

Country

Australia

Phone

+61 7 3176 5817

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
12355	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

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Design and methods of the REMOVAL-HD study: A tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.	2018	https://dx.doi.org/10.1186/s12882-018-0883-8
Embase	A trial evaluating mid cut-off value membrane clearance of albumin and light chains in hemodialysis patients: A safety device study.	2020	https://dx.doi.org/10.1159/000505567

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically