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Trial registered on ANZCTR


Registration number
ACTRN12618001057279
Ethics application status
Approved
Date submitted
19/06/2018
Date registered
25/06/2018
Date last updated
25/03/2021
Date data sharing statement initially provided
4/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Prospective randomised evaluation of prebiotics in organ transplantation to prevent infectious complications - feasibility study
Scientific title
Prospective randomised evaluation of prebiotics in organ transplantation to prevent infectious complications
Secondary ID [1] 295236 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PREBIOTIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney disease 308412 0
Kidney transplant 308447 0
Condition category
Condition code
Renal and Urogenital 307402 307402 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be given information about the study while an inpatient in the transplant ward. They will be given the opportunity to ask questions, to take the information home with them when they leave the hospital and to discuss it with friends, family or others. They will be able to inform us about whether or not they wish to participate at one of their routine clinic visits in the early post-discharge period. This will ensure that the patients are well, stable and able to fully consider their participation in the study.
Participants will be provided with a prebiotic powder or placebo (powder) for eight weeks duration. This will commence when patients are discharged to the outpatient setting following their acute kidney transplant usually a window period of day 5 to day 12. The prebiotic powder will be Green Banana Multi-Resistant Starch which will be provided in-kind by Natural Evolutions (Walkamin, Australia). The placebo will be matched powder (waxy maize, Bulk Nutrients, Grove, Tasmania, Australia). The prebiotic will be administered orally as a powder suspended in water. The prebiotic will be commenced at ½ dose for the first two weeks to enable gut adaption with the full dose given for six weeks. The exact dose will be 7.5g daily for the first two weeks, and then progress to 15g daily for the final six weeks of the study.
Intervention code [1] 301581 0
Treatment: Drugs
Comparator / control treatment
Placebo: matched powder: waxy maize
Control group
Placebo

Outcomes
Primary outcome [1] 306374 0
This is not the primary outcome
The primary outcome for this study is feasibility
a) ability to successfully recruit 60 patients within six months
b) proportion of eligible patients who agree to take part in the study

This will be assessed at the end of the clinical trial
Timepoint [1] 306374 0
Adherence to the Green Banana Resistant Starch will be assessed at the end of the study. The adherence parameter will be measured at the end of the study, i.e. at the eight week mark after kidney transplantation
This will be a secondary outcome now
Adherence to prebiotic supplementation will be defined as
a) proportion of participants adherent to prescribed study therapy (intervention or placebo) over the period of the study
Secondary outcome [1] 348281 0
Laboratory testing
a) proportion of participants providing two stool samples at designated times (the first week and between week four to week eight post kidney transplant) to assess gut microbiota changes (stool sample analysis via shotgun metagenomic sequencing to a target depth of 3Gbp using NovaSeq 6000, 2x150bp paired-end chemistry)

b) proportion of participants providing two blood samples at designated times (the first week and week eight post kidney transplant)
Timepoint [1] 348281 0
Measured at two timepoints
a) the first time point is before the kidney transplant
b) the second time point is at the four week mark after kidney transplant
Secondary outcome [2] 348282 0
Consumer-centred outcomes
a) Changes in the overall quality of life (measured by EQ-5D survey)
Timepoint [2] 348282 0
Measured at the start and at the end of the feasibility study i.e. at baseline and at 8 weeks following kidney transplant
Secondary outcome [3] 348283 0
Tolerance
a) proportion of patients who continue the prebiotic supplementation
b) changes in the Gastrointestinal Symptom Rating Scale
Timepoint [3] 348283 0
Measured at the start, at Week 2 and at the end of the feasibility study i.e. at baseline and at 8 weeks following kidney transplant
Secondary outcome [4] 374520 0
Clinical outcomes
a) proportion of patients with at least one infectious event (infectious event is anything requiring admission or antimicrobial therapy)
b) episodes of rejection and death
Timepoint [4] 374520 0
This will be collected and will be included under 'clinical outcomes' as above.

Eligibility
Key inclusion criteria
Received an acute kidney transplant at the Princess Alexandra Hospital
Aged equal to or greater than 18 years
Able to provide informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Have received radiation to the bowel or large bowel resection
Unable to comply with follow-up
Medically diagnosed and active inflammatory bowel disease
Unwilling or unable to meet the requirements of the protocol
Other medical or social reasons for exclusion at the discretion of the investigators.

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 will be via sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1:1 randomisation between prebiotic and control; randomisation will be prepared by a researcher not involved with treatment allocation and will involve stratification factors of age (<65 years, >=65 years) and sex.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed via descriptive statistics, expressing frequencies (percentages) for categorical data, mean ± standard deviation for continuous normally distributed data, or median [interquartile range] for continuous non-normally distributed data. In addition, confidence intervals will be presented for all descriptive statistics.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/10/2020
Actual
12/10/2020
Date of last participant enrolment
Anticipated
30/04/2021
Actual
Date of last data collection
Anticipated
30/06/2021
Actual
Sample size
Target
60
Accrual to date
45
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 11181 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 23022 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 299824 0
Hospital
Name [1] 299824 0
Metro South Hospital and Health Service Research Support Scheme
Country [1] 299824 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
Department of Nephrology | Division of Medicine
Metro South Hospital and Health Service | Queensland Government
ARTS Building | Princess Alexandra Hospital
199 Ipswich Road | Woolloongabba Qld 4102
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 299179 0
University
Name [1] 299179 0
The University of Queensland
Address [1] 299179 0
Faculty of Medicine
The University of Queensland
Herston Campus
Herston, QLD, 4029
Country [1] 299179 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300704 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 300704 0
Metro South Hospital and Health Service | Queensland Government
Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 300704 0
Australia
Date submitted for ethics approval [1] 300704 0
14/10/2019
Approval date [1] 300704 0
29/05/2020
Ethics approval number [1] 300704 0

Summary
Brief summary
The Transplantation Standardised Outcomes of Nephrology initative has identified infection as a core outcome. Infections are a common complication following kidney transplantation, occurring in more than 65% KTR in Australia, and 40-50% of transplant recipients worldwide. It is expected that the burden of infectious complications will continue to rise based on the growing prevalence of diabetes mellitus and increasing potency of immunosuppressive regimens.

Infectious complications following kidney transplantation are associated with significant mortality. Infection-related mortality occurs in approximately 15-20% of KTR worldwide. In Australia, infection accounts for approximately 22% of deaths in the KTR population, with 75% of these deaths occurring in individuals with a functioning graft.

Infectious complications are associated with prolonged length of hospital stay, admission to intensive care unit and post-acute care, and early hospital readmission. Treating infectious complications following kidney transplantation has been estimated to cost the Australian Government approximately $8 billion between 2009 and 2020, and places additional strain on healthcare providers. The development of strategies to mitigate infectious complications following kidney transplantation is therefore of great importance.

It has been hypothesised that an individual’s gastrointestinal microbiota may modify the risk of infectious complications in KTR. A study of ileal microbiota from nineteen small bowel transplant recipients has highlighted that the relative compositions of multiple bacterial taxa were diagnostic of infectious illness and acute rejection. Additionally, marked disruption of intestinal flora in human recipients of allogenic stem cell grafts was informative of the risk for bacteraemia. There has been minimal work done on the microbiota of KTR and the underlying pathogenesis, clinical consequences and potential for therapeutic manipulation are poorly understood.

As the gastrointestinal microbiota is intimately influenced by diet, the discovery of this relationship between the kidney and gastrointestinal microbiota, known as the kidney-gastrointestinal axis, may be a therapeutic opportunity for nutritional intervention. Thus, this study will explore the benefit of manipulation of the gastrointestinal microbiota, via prebiotic supplementation, examining the feasibility of performing a randomised controlled trial of prebiotic supplementation in reducing infections and gastrointestinal upset in kidney transplant recipients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84538 0
Dr Samuel Chan
Address 84538 0
Department of Nephrology | Division of Medicine
Metro South Hospital and Health Service | Queensland Government
ARTS Building | Princess Alexandra Hospital
199 Ipswich Road | Woolloongabba Qld 4102
AUSTRALIA
Country 84538 0
Australia
Phone 84538 0
+61 7 3176 5080
Fax 84538 0
+61 7 3176 5480
Email 84538 0
samuel.chan@uqconnect.edu.au
Contact person for public queries
Name 84539 0
Dr Samuel Chan
Address 84539 0
Department of Nephrology | Division of Medicine
Metro South Hospital and Health Service | Queensland Government
ARTS Building | Princess Alexandra Hospital
199 Ipswich Road | Woolloongabba Qld 4102
AUSTRALIA
Country 84539 0
Australia
Phone 84539 0
+61 7 3176 5080
Fax 84539 0
+61 7 3176 5480
Email 84539 0
samuel.chan@uqconnect.edu.au
Contact person for scientific queries
Name 84540 0
Dr Samuel Chan
Address 84540 0
Department of Nephrology | Division of Medicine
Metro South Hospital and Health Service | Queensland Government
ARTS Building | Princess Alexandra Hospital
199 Ipswich Road | Woolloongabba Qld 4102
AUSTRALIA
Country 84540 0
Australia
Phone 84540 0
+61 7 3176 5080
Fax 84540 0
+61 7 3176 5480
Email 84540 0
samuel.chan@uqconnect.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
Will need to be discussed with the ethics committee first


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
SourceTitleYear of PublicationDOI
EmbasePREBIOTIC: a study protocol of a randomised controlled trial to assess prebiotic supplementation in kidney transplant recipients for preventing infections and gastrointestinal upset - a feasibility study.2023https://dx.doi.org/10.1186/s40814-023-01236-y
N.B. These documents automatically identified may not have been verified by the study sponsor.