Restrictive versus Liberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury (RELIEVE-AKI): a pilot clinical trial protocol

Abstract

IntroductionObservational studies have linked slower and faster net ultrafiltration (UFNET) rates during kidney replacement therapy (KRT) with mortality in critically ill patients with acute kidney injury (AKI) and fluid overload. To inform the design of a larger randomised trial of patient-centered outcomes, we conduct a feasibility study to examine restrictive and liberal approaches to UFNETduring continuous KRT (CKRT).Methods and analysisThis study is an investigator-initiated, unblinded, 2-arm, comparative-effectiveness, stepped-wedged, cluster randomised trial among 112 critically ill patients with AKI treated with CKRT in 10 intensive care units (ICUs) across 2 hospital systems. In the first 6 months, all ICUs started with a liberal UFNETrate strategy. Thereafter, one ICU is randomised to the restrictive UFNETrate strategy every 2 months. In the liberal group, the UFNETrate is maintained between 2.0 and 5.0 mL/kg/hour; in the restrictive group, the UFNETrate is maintained between 0.5 and 1.5 mL/kg/hour. The three coprimary feasibility outcomes are (1) between-group separation in mean delivered UFNETrates; (2) protocol adherence; and (3) patient recruitment rate. Secondary outcomes include daily and cumulative fluid balance, KRT and mechanical ventilation duration, organ failure-free days, ICU and hospital length of stay, hospital mortality and KRT dependence at hospital discharge. Safety endpoints include haemodynamics, electrolyte imbalance, CKRT circuit issues, organ dysfunction related to fluid overload, secondary infections and thrombotic and haematological complications.Ethics and disseminationThe University of Pittsburgh Human Research Protection Office approved the study, and an independent Data and Safety Monitoring Board monitors the study. A grant from the United States National Institute of Diabetes and Digestive and Kidney Diseases sponsors the study. The trial results will be submitted for publication in peer-reviewed journals and presented at scientific conferences.Trial registration numberThis trial has been prospectively registered with clinicaltrials.gov (NCT05306964). Protocol version identifier and date: 1.5; 13 June 2023.

Precision net ultrafiltration dosing in continuous kidney replacement therapy: a practical approach

“…Higher UF NET rates may be used if the risk of not rapidly treating fluid overload (e.g., severe respiratory distress due to cardiogenic pulmonary edema) outweighs the risk of complications from higher UF NET rates [ 15 ]. In an ongoing clinical trial (NCT05306964), study ICUs are randomized to restrictive or liberal approaches to UF NET [ 44 ]. In the restrictive arm, fluid removal is between 0.5 and 1.5 mL/kg/h of PBW, and in the liberal arm, between 2.0 and 5.0 mL/kg/h of PBW.…”

Response Letter to: Correspondence regarding the article by Murugan et al on Precision net ultrafiltration dosing in continuous kidney replacement therapy: a practical approach

“…Thus, in our calculation of the UF NET rate, we subtracted the volume of fluids simultaneously infused into the patient during a dialysis session in addition to the dialysate and replacement fluids (which can also be given outside the dialysis machine) to determine the precise UF NET rate. This method is more precise in determining the UF NET rate and is currently used in a clinical trial comparing alternative UF NET rate strategies for precision UF NET dosing [ 8 ].…”