Clinical trial NCT03829488: Better Evidence for Selecting Transplant Fluids
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: End Stage Kidney Disease
Delayed Graft Function
Kidney Transplant; Complications
Lead sponsor: The University of Queensland
Sponsor class: OTHER
Collaborators: name: Australian Government Department of Health and Ageing
name: Health Research Council, New Zealand
name: Baxter Healthcare Corporation
First posted: 2019-02-04
Enrollment: 808
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

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

Primary outcomes:
measure: The proportion of participants with Delayed Graft Function
timeFrame: 7 Days
Secondary outcomes:
measure: Early Kidney Transplant Function
timeFrame: a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days
measure: Number of dialysis sessions
timeFrame: First 28 days post-transplant
measure: Total duration of dialysis
timeFrame: 12 Weeks
measure: Creatinine reduction ratio from day 1 to day 2 post-transplant
timeFrame: Day 1 to Day 2 post-transplant
measure: Reduction in serum creatinine of greater than or equal to 10%
timeFrame: First 7 days post-transplant
measure: Serum creatinine trends over 52 weeks
timeFrame: 12 months
measure: Incidence of serum potassium greater than or equal to 5.5 mmol/L
timeFrame: First 48 hours post-transplant
measure: Peak potassium level
timeFrame: First 48 hours post-transplant
measure: Treatment for hyperkalaemia
timeFrame: First 48 hours post-transplant
measure: Incidence of significant fluid overload
timeFrame: Baseline to day 2
measure: Aggregate urine output
timeFrame: Until day 2 post-transplant
measure: Requirement for inotropic support (use of vasopressors or other drugs to maintain adequate blood pressure)
timeFrame: Intra- and post-operatively to Day 2
measure: Number of acute rejection episodes
timeFrame: 12 months
measure: Number of renal transplant biopsies
timeFrame: First 28 days post-transplant
measure: Death from all causes
timeFrame: Up to 52 weeks
measure: Graft survival
timeFrame: 12 months
measure: Graft function
timeFrame: 4, 12, 26 and 52 weeks
measure: Health-related quality of life
timeFrame: Baseline, day 7, day 28, week 12, week 26, and week 52
measure: Length of hospital stay
timeFrame: 12 months
measure: Healthcare resource use
timeFrame: 12 months
measure: Cost-effectiveness
timeFrame: 12 months
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: St Vincent's Hospital (Melbourne) Ltd
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
Study officials:
affiliation: Auckland District Health Board & The University of Auckland
name: Michael Collins, MBChB,FRACP,PhD
role: STUDY_CHAIR
affiliation: Sydney Local Health District & The University of Sydney
name: Steven Chadban, BMed(hons),FRACP,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.