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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03829488




Registration number
NCT03829488
Ethics application status
Date submitted
21/01/2019
Date registered
4/02/2019
Date last updated
30/07/2019

Titles & IDs
Public title
Better Evidence for Selecting Transplant Fluids
Scientific title
An Investigator-initiated, Pragmatic, Registry-based, Multi-centre, Double-blind, Randomised Controlled Trial Evaluating the Effect of Plasmalyte Versus 0.9% Saline on Early Kidney Transplant Function in Deceased Donor Kidney Transplantation
Secondary ID [1] 0 0
ACTRN12617000358347
Secondary ID [2] 0 0
15.02
Universal Trial Number (UTN)
Trial acronym
BEST-Fluids
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End Stage Kidney Disease 0 0
Delayed Graft Function 0 0
Kidney Transplant; Complications 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
Treatment: Drugs - 0.9% SODIUM CHLORIDE 9g/L injection BP

Experimental: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion - Plasma-Lyte 148 (approx. pH 7.4) IV Infusion intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.

Active Comparator: 0.9% SODIUM CHLORIDE 9g/L injection BP - 0.9% saline intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.


Treatment: Drugs: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion is a sterile, clear, non-pyrogenic isotonic solution and when administered intravenously is a source of water, electrolytes and calories. Plasma-Lyte 148 intravenous infusion is indicated as a source of water & electrolytes or as an alkalinising agent.

Treatment: Drugs: 0.9% SODIUM CHLORIDE 9g/L injection BP
Sodium chloride (0.9% saline) infusion is a sterile, non-pyrogenic solution of sodium chloride in Water for Injections. The concentration of sodium chloride is 154mmol/L. Sodium chloride (0.9%) intravenous infusion is indicated for extra-cellular fluid replacement and in the management of metabolic alkalosis in the presence of fluid loss, and for restoring or maintaining the concentration of sodium and chloride ions.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The proportion of participants with Delayed Graft Function - Delayed Graft Function defined as receiving treatment with any form of dialysis in the first seven days after transplant
Timepoint [1] 0 0
7 Days
Secondary outcome [1] 0 0
Early Kidney Transplant Function - Early Kidney Transplant Function, a ranked composite of
Duration of Delayed Graft Function Description: Participants who require dialysis within seven days post-transplant, the time from transplant to the final dialysis treatment in days (up to 84 days/12 weeks) will be ranked from best to worst (longer times are worse).
Rate of recovery of kidney transplant graft function Description: for participants who do not require dialysis, graft function assessed using the creatinine reduction ratio on post-transplant day two (CRR2) will be ranked from best to worst (smaller reductions are worse).
Timepoint [1] 0 0
a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days
Secondary outcome [2] 0 0
Number of dialysis sessions - The number of dialysis sessions
Timepoint [2] 0 0
First 28 days post-transplant
Secondary outcome [3] 0 0
Total duration of dialysis - The total duration of dialysis in days
Timepoint [3] 0 0
12 Weeks
Secondary outcome [4] 0 0
Creatinine reduction ratio from day 1 to day 2 post-transplant - Creatinine reduction ratio from day one to day two measured using serum assay, for those who do not require dialysis within the first 7 days
Timepoint [4] 0 0
Day 1 to Day 2 post-transplant
Secondary outcome [5] 0 0
Reduction in serum creatinine of greater than or equal to 10% - The proportion of subjects with a reduction in serum creatinine of greater than or equal to 10% on three consecutive days in the first 7 days post-transplant
Timepoint [5] 0 0
First 7 days post-transplant
Secondary outcome [6] 0 0
Serum creatinine trends over 52 weeks - Serum creatinine trends measured over 52 weeks
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Incidence of serum potassium greater than or equal to 5.5 mmol/L - Serum potassium greater than or equal to 5.5 mmol/L measured by serum assay
Timepoint [7] 0 0
First 48 hours post-transplant
Secondary outcome [8] 0 0
Peak potassium level - Peak potassium level, measured by serum assay
Timepoint [8] 0 0
First 48 hours post-transplant
Secondary outcome [9] 0 0
Treatment for hyperkalaemia - Treatment for hyperkalaemia with dialysis, Ca2+-gluconate, insulin, beta-agonists, sodium bicarbonate or ion exchange resins in the first 48 hours post-transplant
Timepoint [9] 0 0
First 48 hours post-transplant
Secondary outcome [10] 0 0
Incidence of significant fluid overload - Incidence of significant fluid overload defined as >5% weight gain
Timepoint [10] 0 0
Baseline to day 2
Secondary outcome [11] 0 0
Aggregate urine output - Aggregate urine output until day 2 post-transplant
Timepoint [11] 0 0
Until day 2 post-transplant
Secondary outcome [12] 0 0
Requirement for inotropic support (use of vasopressors or other drugs to maintain adequate blood pressure) - Requirement for inotropic support both intra- and post-operatively to Day 2
Timepoint [12] 0 0
Intra- and post-operatively to Day 2
Secondary outcome [13] 0 0
Number of acute rejection episodes - Number of acute rejection episodes in the first 52 weeks as reported by ANZDATA routine data capture and as assessed by treating physicians
Timepoint [13] 0 0
12 months
Secondary outcome [14] 0 0
Number of renal transplant biopsies - Number of renal transplant biopsies performed in the first 28 days post-transplant
Timepoint [14] 0 0
First 28 days post-transplant
Secondary outcome [15] 0 0
Death from all causes - Death from all causes up to 52 weeks
Timepoint [15] 0 0
Up to 52 weeks
Secondary outcome [16] 0 0
Graft survival - Graft survival and death-censored graft survival as reported by ANZDATA and assessed by treating physician
Timepoint [16] 0 0
12 months
Secondary outcome [17] 0 0
Graft function - Graft function (estimated glomerular filtration rate; eGFR) at 4, 12, 26 and 52 weeks
Timepoint [17] 0 0
4, 12, 26 and 52 weeks
Secondary outcome [18] 0 0
Health-related quality of life - Health-related quality of life measured using EuroQol EQ-5D-5L for adults, and EQ-5D-Y in children under 18 years. EQ-5D has descriptive and visual analogue scale (VAS). Descriptive system consists of five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety/depression. VAS records patient's self-rated health on vertical visual analogue scale with endpoints best to worst health with 0 being worst and 100 being best health.
Timepoint [18] 0 0
Baseline, day 7, day 28, week 12, week 26, and week 52
Secondary outcome [19] 0 0
Length of hospital stay - Length of hospital stay over 12 months using linked data state and country based health data
Timepoint [19] 0 0
12 months
Secondary outcome [20] 0 0
Healthcare resource use - Healthcare resource use over 12 months using linked data state and country based health data
Timepoint [20] 0 0
12 months
Secondary outcome [21] 0 0
Cost-effectiveness - Cost-effectiveness over 12 months using linked data state and country based health data
Timepoint [21] 0 0
12 months

Eligibility
Key inclusion criteria
1. Adult or child with End-Stage Kidney Disease, of any cause, on maintenance dialysis,
or who has pre-dialysis stage 5 chronic kidney disease with an estimated Glomerular
Filtration Rate of <15 mL/min/1.73m2, AND

2. Planned deceased donor kidney transplant from a brain-death (DBD) or circulatory-death
(DCD) organ donor within 24 hours, AND

3. Written informed consent, or consent given by their parent or guardian (if age <18),
or other authorised person
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Planned live donor kidney transplant (except where this is cancelled in favour or
transplantation from a deceased donor)

2. Planned multi-organ transplant (dual or en-bloc kidney transplants are not excluded)

3. Children of weight <20 kg, or a child that the treating physician believes should not
be included in a study of blinded fluids due to their small body size

4. Known hypersensitivity to the trial fluid preparations or packaging

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
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
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [3] 0 0
Westmead Hospital - Sydney
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
St Vincent's Hospital (Melbourne) Ltd - Melbourne
Recruitment hospital [7] 0 0
Austin Health - Melbourne
Recruitment hospital [8] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [9] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Sydney
Recruitment postcode(s) [4] 0 0
4102 - Brisbane
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3065 - Melbourne
Recruitment postcode(s) [7] 0 0
3084 - Melbourne
Recruitment postcode(s) [8] 0 0
3168 - Melbourne
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian Government Department of Health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Health Research Council, New Zealand
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Baxter Healthcare Corporation
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
End-stage kidney disease (ESKD) is a significant, expensive health problem. Kidney
transplantation improves survival, quality of life, and is much cheaper than dialysis
treatment for ESKD. However sometimes kidney transplants from a deceased donor function
poorly after surgery, and a period of continued dialysis is needed, a condition known as
delayed graft function (DGF). In addition to complicating recovery, DGF can adversely affect
long-term kidney function and the health of the recipient.

Intravenous fluids given during and after transplantation (usually 0.9% sodium chloride or
saline) are critical to preserve kidney transplant function, but there is evidence that 0.9%
saline may not be the safest fluid to use due to its high chloride content.

BEST Fluids is a randomised controlled trial that aims to find out whether using a balanced
low-chloride solution - Plasma-Lyte 148® - as an alternative to normal saline in deceased
donor kidney transplantation, will improve kidney transplant function, reduce the impact of
DGF, and improve long-term outcomes for patients.
Trial website
https://clinicaltrials.gov/show/NCT03829488
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Collins, MBChB,FRACP,PhD
Address 0 0
Auckland District Health Board & The University of Auckland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michael Collins, MBChB,FRACP,PhD
Address 0 0
Country 0 0
Phone 0 0
+64 9 367 0000
Fax 0 0
Email 0 0
michael.collins@adhb.govt.nz
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03829488