Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000531617
Ethics application status
Approved
Date submitted
26/04/2023
Date registered
19/05/2023
Date last updated
11/06/2024
Date data sharing statement initially provided
19/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Determining the utility of uraemic toxins in peritoneal dialysis to optimise patient care
Scientific title
Determining the utility of uraemic toxins in peritoneal dialysis to optimise patient care: interventional study looking at whether a high fibre diet reduces protein-bound uraemic toxins (PBUT) in peritoneal dialysis (PD) patients.
Secondary ID [1] 309640 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
TREAT PD (deTeRmining thE utility of urAemic Toxins in Peritoneal Dialysis to optimise patient care)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Failure 329628 0
Peritoneal Dialysis 329629 0
Condition category
Condition code
Renal and Urogenital 326554 326554 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised controlled study using a parallel group design where incident PD patients (those who have started PD in the 3 months prior to the study) will be recruited. Patients will be randomised into two groups: those receiving dianeal (n=30), and those on dianeal receiving a high fibre diet (n=30).

The dianeal with high fibre group/ Intervention arm : This group of participants will receive dianeal PD solutions (dianeal by Baxter) with dextrose concentrations of 0.55%, 1.5%, 2.5% and 4.25%. They will receive these solutions according to their clinical need without a strict prescription (so a minimum prescription of 2L exchange for 4 hours per day to a maximum of 16L per day) for 12 months. Each participant in the intervention group will self-administer these solutions as part of their PD dialysis routine. In addition, they will have a fibre supplement with resistant starch in the form of wheat dextrin (Benefiber). They will start with 1 sachet (1 sachet= 3g) per day for 1 week before increasing the dose by 1 sachet per week over 4 weeks until any of the following targets have been reached; maximum recommended Benefiber dose of 4 sachets daily (12g/day), recommended daily fibre intake of 25g/day or the participants’ maximum tolerated amount. The participants will be on this treatment for 12 months or their maximum tolerated time. The monitoring and adherence of fibre intake will be monitored with phone interviews and a fibre diary by researchers via phone calls and/or face-to-face appointments every 8 weeks.
Dianeal (Baxter) PD fluid contains glucose, sodium chloride, sodium lactate, magnesium chloride hexahydrate and calcium chloride dihydrate

All the interventions will be delivered by the study team with minimum 5 years of experience with conducting a trial. Information and delivery will be mostly by face-to-face consultations but also via telehealth in some circumstances at the study locations (Eastern Health and Monash Health)
Measurements of uraemic toxins (water soluble, middle-molecule and protein-bound uraemic toxins), renal parameters (measured kidney function, urine output) and patient focused outcomes (patient health related quality of life measure using EQ-5D-5L questionnaire, patient’s symptom and mood score using IPOS-renal questionnaire and an assessment of physical function using hand grip strength and timed chair-to-stand test) will be measured.
Intervention code [1] 325891 0
Treatment: Other
Comparator / control treatment
The control group is the dianeal group/control arm : This group of participants will receive dianeal PD solutions with dextrose concentrations of 0.55%, 1.5%, 2.5% and 4.25%. They will receive these solutions according to their clinical need without a strict prescription (so a minimum prescription of 2L exchange for 4 hours per day to a maximum of 16L per day) for 12 months. Each participant in the intervention group will self-administer these solutions as part of their PD dialysis routine. They will have no interventions to their diet. Participants will be on this treatment for a minimum period of 12 months.
Dianeal (Baxter) PD fluid contain glucose, sodium chloride, sodium lactate, magnesium chloride hexahydrate and calcium chloride dehydrate
All participants would have received PD training prior to this study.
All the interventions will be delivered by the study team with minimum 5 years of experience with conducting a trial. Information and delivery will be mostly by face-to-face consultations but also via telehealth in some circumstances at the study locations (Eastern Health and Monash Health)
Measurements of uraemic toxins (water soluble, middle-molecule and protein-bound uraemic toxins), renal parameters (measured kidney function, urine output) and patient focused outcomes (patient health related quality of life measure using EQ-5D-5L questionnaire, patient symptom and mood score using IPOS-renal questionnaire and an assessment of physical function using hand grip strength and timed chair-to-stand test) will be measured.
Control group
Active

Outcomes
Primary outcome [1] 334495 0
Change in indoxyl-sulphate level in blood, urine and peritoneal dialysis dialysate
Timepoint [1] 334495 0
12 months post-intervention commencement
Primary outcome [2] 334632 0
Change in p-cresyl sulphate level in blood, urine and peritoneal dialysis dialysate
Timepoint [2] 334632 0
12 months post-intervention commencement
Secondary outcome [1] 420851 0
Any change in patient health related quality of life measure using EQ-5D-5L questionnaire
Timepoint [1] 420851 0
12 months post-intervention commencement
Secondary outcome [2] 420852 0
Any change in patient's symptom and mood score using Integrated Palliative Outcome Score (IPOS) renal questionnaire.
Timepoint [2] 420852 0
12 months post-intervention commencement
Secondary outcome [3] 420853 0
Any change in physical function assessed using hand grip strength determined using a dynanometer

Timepoint [3] 420853 0
12 months post-intervention commencement
Secondary outcome [4] 420854 0
Any change in kidney function using serum creatinine (umol/L) and estimated glomerular filtration rate (eGFR) using ml/min/1.73m2

Timepoint [4] 420854 0
12 months post-intervention commencement
Secondary outcome [5] 421461 0
Any change in physical function assessed using the timed chair-to-stand test
Timepoint [5] 421461 0
12 months post-intervention commencement
Secondary outcome [6] 421462 0
Any change in 24-hour urine output (ml/day) using a 24-hour urine collection bottle with graduated labelling for volume.
Timepoint [6] 421462 0
12 months post-intervention commencement

Eligibility
Key inclusion criteria
Age greater than or equal to 18
Incident Peritoneal Dialysis (PD) patients (Patient who have been newly started on PD in the last 3 months)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are currently pregnant
Patients with Cognitive Impairment or learning differences that are unable to consent
Patient with active malignancy

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)
Allocation concealment by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical power: Given the pilot nature of this study and the lack of data regarding uraemic toxin removal by different PD fluids, power calculations was not possible.

One of the main studies looking at fibre supplementation in HD patients by Sirich et al (ref below) included a total of 56 HD patients after randomising the patients to either receiving resistant starch or placebo (28 patients in each group) where they demonstrated a 29% reduction in PBUT levels in the resistant starch group. Taking this into account, we have estimated that a sample size of n=40 is needed to detect a 25% reduction in PBUT measurements, with 90% power and a 2-sided alpha of 0.05. To allow for the high turnover rate in PD (where patients transition onto HD or have a transplant) and dropout rate, we have opted to recruit up to 90 participants (30 patients in each group).
In addition, Eastern and Monash Renal units typically have 40-80 incident PD patients each year. Assuming a 50% consent rate, it will take 1-2 years to recruit a target of 90 participants.

Statistical analysis: Descriptive statistics will be used to determine the contributions of kidney and dialysis on removal of uraemic toxins. Comparisons of toxin removal between different groups will be made by Student’s t tests.


Reference
Sirich, Tammy L.*; Plummer, Natalie S.*; Gardner, Christopher D.*; Hostetter, Thomas H.†; Meyer, Timothy W.*. Effect of Increasing Dietary Fiber on Plasma Levels of Colon-Derived Solutes in Hemodialysis Patients. Clin J Am Soc Nephrol 9(9):p 1603-1610, September 2014. | DOI: 10.2215/CJN.00490114

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/10/2023
Actual
19/10/2023
Date of last participant enrolment
Anticipated
6/01/2025
Actual
Date of last data collection
Anticipated
6/01/2026
Actual
Sample size
Target
90
Accrual to date
16
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24539 0
Eastern Health - Box Hill
Recruitment hospital [2] 24540 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [3] 24541 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 40133 0
3128 - Box Hill
Recruitment postcode(s) [2] 40135 0
3168 - Clayton
Recruitment postcode(s) [3] 40134 0
3175 - Dandenong

Funding & Sponsors
Funding source category [1] 313593 0
Hospital
Name [1] 313593 0
Eastern Health Clinical School
Country [1] 313593 0
Australia
Funding source category [2] 313664 0
Hospital
Name [2] 313664 0
Monash Medical Centre
Country [2] 313664 0
Australia
Primary sponsor type
Hospital
Name
Eastern Health Clinical School
Address
Department of Nephrology, Eastern Health
5, Arnold Street,
Box Hill
Victoria
3128
Country
Australia
Secondary sponsor category [1] 315378 0
Hospital
Name [1] 315378 0
Monash Medical Centre
Address [1] 315378 0
Department of Nephrology, Monash Health
246, Clayton Road
Clayton
Victoria
3168
Country [1] 315378 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312770 0
Eastern Health Ethics committee
Ethics committee address [1] 312770 0
Eastern health Research Ethics and Governance
5, Arnold Street
Box Hill
Victoria
3128
Ethics committee country [1] 312770 0
Australia
Date submitted for ethics approval [1] 312770 0
12/06/2023
Approval date [1] 312770 0
08/08/2023
Ethics approval number [1] 312770 0
Ethics committee name [2] 312891 0
Monash Health Ethics Committee
Ethics committee address [2] 312891 0
246, Clayton Road
Clayton
Victoria
3168
Ethics committee country [2] 312891 0
Australia
Date submitted for ethics approval [2] 312891 0
12/06/2023
Approval date [2] 312891 0
11/08/2023
Ethics approval number [2] 312891 0

Summary
Brief summary
Peritoneal dialysis (PD) removes toxins that rise during kidney failure. Historically, we looked at removal of small water-soluble molecules as a surrogate marker of dialysis effectiveness. However, given its poor relationship with patient outcomes, recent guidelines have moved away from these targets and is now focusing on patient reported outcomes. Moreover, protein-bound uraemic toxins (PBUT), which are poorly removed in dialysis, may have more of a role in patient outcomes. Additionally, studies in haemodialysis and chronic kidney disease have shown that high-fibre diet may help reduce the generation of these PBUTs but studies are lacking in the PD population.
We will determine effects of PBUT removal on patient outcomes (quality of life measure using EQ-5D-5L, symptoms and mood score using IPOS-renal and an assessment of physical function including hand-grip strength and timed chair-to-stand test) and preservation of residual kidney function. We will also look at the effects of increased fibre intake on PBUT levels and above-mentioned patient outcomes in a group of PD patients.
We hypothesise that a high fibre diet will reduce PBUT generation in the PD population. We hypothesise that this reduction in PBUT levels will correlate with better patient outcomes and preservation of residual kidney function.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125850 0
Dr Aruni Malaweera
Address 125850 0
Department of Renal Medicine, Eastern Health
5, Arnold Street
Box Hill
Victoria
3128
Country 125850 0
Australia
Phone 125850 0
+61 413104081
Fax 125850 0
Email 125850 0
aruni.malaweera@monash.edu
Contact person for public queries
Name 125851 0
Dr Aruni Malaweera
Address 125851 0
Department of Renal Medicine, Eastern Health
5, Arnold Street
Box Hill
Victoria
3128
Country 125851 0
Australia
Phone 125851 0
+61 90949563
Fax 125851 0
Email 125851 0
aruni.malaweera@monash.edu
Contact person for scientific queries
Name 125852 0
Dr Aruni Malaweera
Address 125852 0
Department of Renal Medicine, Eastern Health
5, Arnold Street
Box Hill
Victoria
3128
Country 125852 0
Australia
Phone 125852 0
+61 413104081
Fax 125852 0
Email 125852 0
aruni.malaweera@monash.edu

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?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.