LoW Dose-Intensity vs. Standard Dose-Intensity COntinuous Renal ReplaceMent Therapy in Critically Ill Patients (WISDOM)

University of Alberta

Status: Enrolling

Conditions: Acute Kidney Injury; Dialysis; Complications

Treatments: Device: Continuous Renal Replacement Therapy (CRRT)

Study type: Interventional

Funder types: Other

Identifiers

NCT06446739

00140224

Details and patient eligibility

About

An estimated 10-15% of critically ill patients with acute kidney failure in the intensive care unit receive acute dialysis therapy. The majority of these patients initially receive a continuous form of dialysis therapy call continuous renal replacement therapy (CRRT). Prior studies have suggested that higher CRRT dose-intensity improved health outcomes for these patients; however, this was not found in high-quality clinical trials. These more recent trials suggested a lower range of dose-intensity compared with the higher range as the new standard of care. This was incorporated into guidelines. To date, no clinical trials have evaluated this lower range and specifically, it is plausible that an even lower dose-intensity of CRRT may be well tolerated, safe, associated with similar outcomes and be more cost-effective. This is the objective of the WISDOM trial, to compare the guideline standard with lower dose-intensity among patients who are started on CRRT in the intensive care unit.

Full description

Purpose: To primarily determine whether a lower CRRT dose-intensity in critically ill patients with acute kidney injury (AKI) is non-inferior to standard CRRT dose-intensity and to secondarily determined whether lower CRRT dose intensity will shorten total CRRT duration and improve kidney recovery compared with standard CRRT dose-intensity.

Hypothesis: The primary hypothesis of the WISDOM trial is that lower CRRT dose-intensity is non-inferior to current standard guideline-directed CRRT dose-intensity for critically ill patients with AKI with respect to duration of CRRT and successful liberation from RRT and kidney recovery. The secondary hypothesis of the WISDOM trial is that lower dose-intensity is superior to current standard guideline-directed CRRT dose-intensity for critically ill patients with AKI with respect to duration of CRRT and successful liberation from RRT and kidney recovery.

Justification: No randomized controlled trial (RCT) to date has specifically evaluated the lower dose-intensity threshold for critically ill patients receiving CRRT. Specifically, there has been no specific evidence or guidance on the minimum dose-intensity targets for patients receiving CRRT. This is important for several reasons. First, CRRT is an invasive, resource intensive and expensive therapy. As such, there should be a concerted effort to minimize time on RRT and facilitate early recovery and weaning. Second, abundant evidence derived from secondary analyses have suggested that higher CRRT dose-intensity can propagate oliguria, prolong CRRT therapy and delay kidney recovery. This would imply that lower dose-intensity may facilitate kidney recovery and earlier weaning from CRRT. Third, there may be added implications of higher dose-intensity, including prolongation of non-renal organ support, such as delay in weaning from invasive mechanical ventilation. Fourth, evidence derived from observational registries show that lower CRRT dose-intensity, in the range proposed in this trial, provides comparable efficacy in azotemic, metabolic and acid-base homeostasis with similar outcomes. Observational data have suggested a prescribed CRRT dose-intensity of 15 mL/kg/hr may be sufficient for metabolic and azotemic control and is not associated with worse outcomes compared with guideline directed dose-intensity. This is lower quality evidence, however, implies that lower dose-intensity may be acceptable and safe. Fifth, it is plausible that following a short period of metabolic stabilization with CRRT, the minimum recommended CRRT dose-intensity of 20-25 mL/kg/hr may be excessive and have unmeasurable harm (e.g., excessive clearance of electrolytes, micronutrients, and medications [antimicrobials]). Finally, the prescription of a lower CRRT dose-intensity may have meaningful impact on reducing bedside nursing workload (e.g., fewer replacement solution bag changes) and reducing costs attributable to CRRT (e.g., lower effluent rates will reduce total replacement solution utilized).

While this proposal outlines a pilot feasibility trial, it is aimed at performing a larger rigorous RCT that will generate generalizable and high-quality evidence to impact clinical practice. The findings of the main phase of the WISDOM trial will provide clearer evidence to guide the prescription of a minimal dose-intensity for patients receiving CRRT. While this may be an effluent dose of 20-25 mL/kg/hr, it is entirely plausible that this will be a lower dose-intensity.

Objectives: The overall WISDOM trial program will address whether a lower CRRT dose-intensity in critically ill patients with AKI is non-inferior to standard CRRT dose-intensity and will secondarily address whether lower CRRT dose intensity will shorten total CRRT duration and improve kidney recovery compared with standard CRRT dose-intensity.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age ≥ 18 years
• weight ≥ 55 kg
• plan to initiate CRRT or within 24 hours of having started CRRT for AKI
• expected to survive and receive CRRT for a duration of ≥ 48 hours
• able to provide informed consent or have an authorized representative provide consent after being informed on the details and risks of the trial unless a deferred consent process is approved by local Research Ethics Board (REB).

Exclusion criteria

• indication for sustained higher dose-intensity CRRT as designated by the attending clinicians
• end-stage kidney disease receiving maintenance dialysis
• receipt of any RRT for AKI during the current hospitalization
• inability to comply with the requirements of the study protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

100 participants in 2 patient groups

Low dose-intensity

Experimental group

Description:

The intervention arm will consist of low dose-intensity CRRT, defined as the hourly delivery of a total effluent of 10-15 mL/kg/hr while receiving CRRT. The intervention dose-intensity is based on the rationale that 10-15 mL/kg/hr is the lower threshold of dose-intensity currently provided in clinical practice and prior observational data showing this threshold is tolerated and safe.

Treatment:

Device: Continuous Renal Replacement Therapy (CRRT)

Standard dose-intensity

Active Comparator group

Description:

The control arm will receive a dose-intensity CRRT of 25-30 mL/kg/hr while receiving CRRT, aligned with local practice and information by international clinical practice guidelines. The control dose-intensity is based on the rationale that this is currently recommended in clinical practice guidelines and is commonly applied in routine practice.

Treatment:

Device: Continuous Renal Replacement Therapy (CRRT)