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

Elaine M Pascoe, Steven J Chadban, Magid A Fahim, Carmel M Hawley, David W Johnson, Michael G Collins, BEST-fluids Investigators and the Australasian Kidney Trials Network, Elaine M Pascoe, Steven J Chadban, Magid A Fahim, Carmel M Hawley, David W Johnson, Michael G Collins, BEST-fluids Investigators and the Australasian Kidney Trials Network

Abstract

Background: Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial.

Methods and design: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome.

Discussion: BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019.

Keywords: 0.9% saline; Delayed graft function; End-stage kidney disease; Intravenous fluids; Kidney transplantation; Plasma-Lyte 148; Randomised controlled trial; Statistical analysis plan.

Conflict of interest statement

MC has received research support from Baxter Healthcare Pty Ltd., the manufacturer of Plasmalyte, through a Baxter Investigator Initiated Research grant that provided fluids for this trial (commercial value of US $36,270). EP is an employee of the Sponsor, The University of Queensland. DJ has received consultancy fees, research grants, speaker’s honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from Astra Zeneca and AWAK, speaker’s honoraria and travel sponsorships from ONO, and BI & Lilly, and travel sponsorships from ONO and Amgen. CH has received research grants from Baxter and NHMRC related to the current project. The other authors declare that they have no competing interests.

© 2022. The Author(s).

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