Overview of the study protocols and statistical analysis plan for the saline versus Plasma-Lyte 148 for intravenous fluid therapy (SPLIT) research program

Background: 0.9 saline is the most commonly used intravenous (IV) fluid in the world but recent data raise the possibility that, compared with buffered crystalloid fluids such as Plasma-Lyte 148, the administration of 0.9 saline might increase the risk of developing acute kidney injury. Objective: To provide an overview of the study protocols and statistical analysis plan for the six studies making up the (0.9 Saline v Plasma-Lyte 148 for Intravenous Fluid Therapy (SPLIT) research program. Methods: The SPLIT study consists of six integrated clinical trials, including a double-blind, cluster, randomised, double-crossover study in intensive care unit patients, incorporating two nested studies within it; an open-label, before-and-after study in emergency department (ED) patients; a single-centre, double-blind, crossover trial in major surgical patients; and a randomised, double-blind study in ICU patients. All studies focus on biochemical and renal outcomes but will also provide preliminary data on patient-centred outcomes including inhospital mortality and requirements for dialysis. Results and conclusion: The SPLIT study program will provide preliminary data on the comparative effectiveness of using 0.9 saline v Plasma-Lyte 148 for IV fluid therapy in ED, surgical and ICU patients.