The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration. Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment. Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy. Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).