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End Stage Kidney DiseasePhase 3BEST-FluidsNCT03829488

Better Evidence for Selecting Transplant Fluids

A Phase 3 study testing Plasma-Lyte 148 (approx. pH 7.4) IV Infusion and 0.9% SODIUM CHLORIDE 9g/L injection BP in people with End Stage Kidney Disease and Delayed Graft Function, run by The University of Queensland at 18 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion and 0.9% SODIUM CHLORIDE 9g/L injection BP
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
808 participants
Where
18 sitesin 2 countries
Study dates
26 Jan 2018to 3 May 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
  • Planned deceased donor kidney transplant from a brain-death (DBD) or circulatory-death (DCD) organ donor within 24 hours, AND
  • Written informed consent, or consent given by their parent or guardian (if age <18), or other authorised person

Who cannot join

  • Planned live donor kidney transplant (except where this is cancelled in favour or transplantation from a deceased donor)
  • Planned multi-organ transplant (dual or en-bloc kidney transplants are not excluded)
  • 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
  • Known hypersensitivity to the trial fluid preparations or packaging

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

Australia14 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Queensland Children's Hospital

    Brisbane, Queensland, 4101

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • St Vincent's Hospital (Melbourne) Ltd

    Melbourne, Victoria, 3065

  • Austin Health

    Melbourne, Victoria, 3084

  • Monash Children's Hospital

    Melbourne, Victoria, 3168

  • Monash Medical Centre

    Melbourne, Victoria, 3168

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • Sir Charles Gairdner Hospital

    Perth, Western Australia, 6009

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

  • Prince of Wales Hospital

    Sydney, New South Wales, 2031

  • Royal Prince Alfred Hospital

    Sydney, New South Wales, 2050

  • The Children's Hospital at Westmead

    Sydney, New South Wales, 2145

  • Westmead Hospital

    Sydney, New South Wales, 2145

Other trials in Australia

New Zealand4 sites

  • Auckland City Hospital

    Auckland, 1142

  • Starship Children's Hospital

    Auckland, 1142

  • Christchurch Hospital

    Christchurch, 8011

  • Wellington Hospital

    Wellington, 6021

Other trials in New Zealand

About this study

Official 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

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.

Read the detailed description

End-stage kidney disease is a significant public health problem worldwide, and its treatment imposes a high healthcare burden and cost. Kidney transplantation is considered the best treatment for ESKD, offering improved survival and quality of life at significantly lower cost that dialysis. However, many kidney transplants fail prematurely due in part due to injury sustained at the time of transplantation. Delayed graft function (DGF), i.e. the requirement for dialysis early after transplantation, affects approximately 30% of deceased donor kidney transplants, and increases the risk of graft failure and mortality.

Intravenous fluids are a critical, albeit inexpensive, aspect of care that impacts early transplant function with normal (0.9%) saline the current standard care at most centres. However, normal saline may in fact be harmful in the setting of kidney transplantation due to its high chloride content relative to plasma, causing metabolic acidosis, acute kidney injury and thus potentially increasing the risk of DGF. Utilising a balanced low-chloride crystalloid solution such as Plasma-Lyte 148® (Plasmalyte) as an alternative to 0.9% saline may therefore improve outcomes after kidney transplantation.

The BEST-Fluids study is an investigator-initiated, pragmatic, registry-based, multi-centre, double -blind randomised, controlled trial. The primary objective of the study is to evaluate the effect in deceased donor kidney transplant recipients of intravenous therapy with Plasmalyte versus 0.9% saline, commencing pre-operatively and continuing until intravenous fluids are no longer required or 48 hours post-transplant (whichever is earliest), on DGF, defined as the requirement for dialysis in the first seven days post-transplant.

Patients admitted for a deceased donor kidney transplant at participating centres will be invited to participate in the study prior to transplant surgery. Following informed consent, participants will be randomised to receive either blinded Plasmalyte or blinded 0.9% saline for all intravenous fluid therapy purposes until 48 hours post-transplant. The volume and rate of fluid therapy will be determined by treating clinicians; all other treatments will be as per local standard of care. Participants will be enrolled, randomised and followed up using ANZDATA, the Australia \& New Zealand Dialysis \& Transplant Registry.

The trial was prospectively registered with Australia New Zealand Clinical Trials Registry (ANZCTR) on 08/03/2017 (ACTRN12617000358347).

Being tested
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion, 0.9% SODIUM CHLORIDE 9g/L injection BP
Medical subject headings
Kidney Failure, Chronic, Delayed Graft Function

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Plasma-Lyte 148 (approx. pH 7.4) IV InfusionDrug

    Also called Plasma-Lyte 148®, Plasmalyte, Balanced crystalloid solution

    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.

  • 0.9% SODIUM CHLORIDE 9g/L injection BPDrug

    Also called 0.9% saline, Normal saline, Isotonic saline

    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.

Study groups in NCT03829488
Study groupRoleWhat they receive
Plasma-Lyte 148 (approx. pH 7.4) IV InfusionExperimentalPlasma-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.
Receives: Drug: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
0.9% SODIUM CHLORIDE 9g/L injection BPActive comparator0.9% 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.
Receives: Drug: 0.9% SODIUM CHLORIDE 9g/L injection BP

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 7 Days

Secondary outcomes (21)

  1. Early Kidney Transplant Function

    Early Kidney Transplant Function, a ranked composite of

    1. 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).
    2. 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).

    Measured: a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days

  2. Number of dialysis sessions

    The number of dialysis sessions

    Measured: First 28 days post-transplant

  3. Total duration of dialysis

    The total duration of dialysis in days

    Measured: 12 Weeks

  4. 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

    Measured: Day 1 to Day 2 post-transplant

  5. 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

    Measured: First 7 days post-transplant

  6. Serum creatinine trends over 52 weeks

    Serum creatinine trends measured over 52 weeks

    Measured: 12 months

  7. 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

    Measured: First 48 hours post-transplant

  8. Peak potassium level

    Peak potassium level, measured by serum assay

    Measured: First 48 hours post-transplant

  9. 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

    Measured: First 48 hours post-transplant

  10. Incidence of significant fluid overload

    Incidence of significant fluid overload defined as >5% weight gain

    Measured: Baseline to day 2

  11. Aggregate urine output

    Aggregate urine output until day 2 post-transplant

    Measured: Until day 2 post-transplant

  12. 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

    Measured: Intra- and post-operatively to Day 2

  13. 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

    Measured: 12 months

  14. Number of renal transplant biopsies

    Number of renal transplant biopsies performed in the first 28 days post-transplant

    Measured: First 28 days post-transplant

  15. Death from all causes

    Death from all causes up to 52 weeks

    Measured: Up to 52 weeks

  16. Graft survival

    Graft survival and death-censored graft survival as reported by ANZDATA and assessed by treating physician

    Measured: 12 months

  17. Graft function

    Graft function (estimated glomerular filtration rate; eGFR) at 4, 12, 26 and 52 weeks

    Measured: 4, 12, 26 and 52 weeks

  18. 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.

    Measured: Baseline, day 7, day 28, week 12, week 26, and week 52

  19. Length of hospital stay

    Length of hospital stay over 12 months using linked data state and country based health data

    Measured: 12 months

  20. Healthcare resource use

    Healthcare resource use over 12 months using linked data state and country based health data

    Measured: 12 months

  21. Cost-effectiveness

    Cost-effectiveness over 12 months using linked data state and country based health data

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start26 Jan 2018
  3. Primary completion29 Jul 2021
  4. Study completion3 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
808 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829488
Sponsor's protocol ID
AKTN 15.02
Other IDs
ACTRN12617000358347
Acronym
BEST-Fluids
Status last verified
Sep 2021
First submitted
21 Jan 2019
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Yes Individual participant data that underlie the results reported in the primary publication, after de-identification (text, tables, figures and appendices) will be available for individual participant data meta-analysis.

Publications

  • Collins MG, Fahim MA, Pascoe EM, Hawley CM, Johnson DW, Varghese J, Hickey LE, Clayton PA, Dansie KB, McConnochie RC, Vergara LA, Kiriwandeniya C, Reidlinger D, Mount PF, Weinberg L, McArthur CJ, Coates PT, Endre ZH, Goodman D, Howard K, Howell M, Jamboti JS, Kanellis J, Laurence JM, Lim WH, McTaggart SJ, O'Connell PJ, Pilmore HL, Wong G, Chadban SJ; BEST-Fluids Investigators; Australasian Kidney Trials Network. Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2023 Jul 8;402(10396):105-117. doi: 10.1016/S0140-6736(23)00642-6. Epub 2023 Jun 18.

    PubMed 37343576

  • Pascoe EM, Chadban SJ, Fahim MA, Hawley CM, Johnson DW, Collins MG; BEST-fluids Investigators and the Australasian Kidney Trials Network. Statistical analysis plan for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a randomised controlled trial of the effect of intravenous fluid therapy with balanced crystalloid versus saline on the incidence of delayed graft function in deceased donor kidney transplantation. Trials. 2022 Jan 18;23(1):52. doi: 10.1186/s13063-021-05989-w.

    PubMed 35042554

  • Collins MG, Fahim MA, Pascoe EM, Dansie KB, Hawley CM, Clayton PA, Howard K, Johnson DW, McArthur CJ, McConnochie RC, Mount PF, Reidlinger D, Robison L, Varghese J, Vergara LA, Weinberg L, Chadban SJ; BEST-Fluids Investigators and the Australasian Kidney Trials Network. Study Protocol for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a pragmatic, registry-based, multi-center, double-blind, randomized controlled trial evaluating the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on delayed graft function in deceased donor kidney transplantation. Trials. 2020 May 25;21(1):428. doi: 10.1186/s13063-020-04359-2.

    PubMed 32450917

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Plasma-Lyte 148 (approx. pH 7.4) IV Infusion and 0.9% SODIUM CHLORIDE 9g/L injection BP in people with End Stage Kidney Disease and Delayed Graft Function, run by The University of Queensland at 18 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of participants with Delayed Graft Function (time frame: 7 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03829488, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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