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

Abstract

Introduction: Observational studies have linked slower and faster net ultrafiltration (UF_NET) 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 UF_NET during continuous KRT (CKRT).

Methods and analysis: This 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 UF_NET rate strategy. Thereafter, one ICU is randomised to the restrictive UF_NET rate strategy every 2 months. In the liberal group, the UF_NET rate is maintained between 2.0 and 5.0 mL/kg/hour; in the restrictive group, the UF_NET rate is maintained between 0.5 and 1.5 mL/kg/hour. The three coprimary feasibility outcomes are (1) between-group separation in mean delivered UF_NET rates; (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 dissemination: The 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 number: This trial has been prospectively registered with clinicaltrials.gov (NCT05306964). Protocol version identifier and date: 1.5; 13 June 2023.

Keywords: Acute renal failure; Adult intensive & critical care; Clinical Trial; Dialysis.

Figure 1

The stepped-wedged cluster randomised trial design. All ICUs start with the liberal UF_NET rate group (light blue cell). After the first 6 months (period 1) and every 2 months thereafter (periods 2–12), one ICU is randomly allocated to the restrictive UF_NET rate group (dark blue cell). ICU, intensive care units; UF_NET, net ultrafiltration.

Figure 2

Screening and assessment of attending physician equipoise. Attending physician equipoise for net fluid removal rate was evaluated two times per day for patients meeting inclusion and none of the exclusion criteria. AKI, acute kidney injury; CKRT, continuous kidney replacement therapy; CMO, comfort measures only; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; KRT, kidney replacement therapy; VAD, ventricular assist device.

Figure 3

The study intervention. Fluid removal will not be started until the mean arterial pressure (MAP)≥65 mm Hg with or without the need for vasopressors. In either group, the initial UF_NET rate will be set at 0.5 mL/kg/hour and then increased 0.5 mL/kg/hour, until the target UF_NET rate range is reached. Net fluid removal can be stopped at any time and reinitiated as tolerated by the patient. The UF_NET rate is calculated based on the allocation to the intervention group, predicted body weight and rate of fluids infused into the patient. CKRT, continuous kidney replacement therapy; UF_NET, net ultrafiltration.