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

Acute Kidney Injury Clinical Trial

— WISDOM  

Official title:

LoW Dose-Intensity vs. Standard Dose-Intensity COntinuous Renal ReplaceMent Therapy in Critically Ill Patients (WISDOM): A Pilot Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06446739
• Other study ID #: 00140224
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: University of Alberta
• Contact: Sean M Bagshaw, MD
• Phone: 780-248-1256
• Email: bagshaw[@]ualberta.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 continuous for 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.

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. This pilot trial will specifically evaluate the feasibility and tolerability of lower versus 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: July 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age > 18 years

• clinical team decision to initiate CRRT associated with AKI

• within 18 hours of commencement of CRRT

• expected to 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 waiver of consent process is approved by local Research Ethics Board (REB).

Exclusion Criteria:

• absolute indication for higher dose-intensity CRRT

• end-stage kidney disease receiving maintenance dialysis

• inability to comply with the requirements of the study protocol.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Dialysis; Complications

Intervention

Device:
• Continuous Renal Replacement Therapy (CRRT)
Continuous Renal Replacement Therapy (CRRT) is a continuous form of acute renal replacement (hemofiltration/dialysis) therapy provided to critically ill patients with multi-organ dysfunction receiving life support in the intensive care unit (ICU).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Daily bicarbonate while receiving CRRT, an average of 1 month.	Physiological and biochemical outcomes.	Through study completion, at 90-days.
Other	Daily serum phosphate while receiving CRRT, an average of 1 month	Physiological and biochemical outcomes.	Through study completion, at 90-days.
Other	Daily serum urea while receiving CRRT, an average of 1 month	Physiological and biochemical outcomes.	Through study completion, at 90-days.
Other	The total treatment time per day while receiving CRRT following randomization.	Process of care measures.	Through study completion, at 90-days.
Other	The number of planned and unplanned hemofilter/circuit replacements while receiving CRRT following randomization.	Process of care measures.	Through study completion, at 90-days.
Other	The lowest and higher CRRT dose-intensity delivered for any given hour following randomization.	Process of care measures.	While receiving CRRT, an average of 1 month.
Other	The proportion of hours of CRRT when the dose-intensity is in the target range following randomization.	Process of care measures.	Through study completion, at 90-days.
Other	Occurrence of adverse and serious adverse events.	Safety measures.	Through study completion, at 90-days.
Other	Occurrence of adverse events and serious adverse events leading to discontinuation of the trial intervention.	Safety measures.	Through study completion, at 90-days.
Other	RRT-free days at 90-days.	Clinical Outcomes.	Through study completion, at 90-days.
Primary	Difference in delivered CRRT dose-intensity	This pilot trial will target detection of a minimum difference of 10 mL/kg/hr in delivered dose-intensity.	Through study completion, an average of 1 month.
Secondary	Feasibility - consent rate	Consent rate for participation by patient or surrogate decision-maker (SDM).	Through study completion, at 90-days.
Secondary	Feasibility - time to enrollment	Time from eligibility (e.g., starting RRT) to randomization.	During active recruitment into the trial, approximately 1 year.
Secondary	Feasibility - adherence to prescribed CRRT dose-intensity	Protocol adherence for allocated CRRT dose-intensity.	Through study completion, at 90-days.
Secondary	Feasibility - ascertainment to delivered CRRT process measures	Ability to capture delivered CRRT dose-intensity measures.	Through study completion, at 90-days.
Secondary	Feasibility - outcome ascertainment	Ability to capture patient and kidney endpoints at 90-days.	Through study completion, at 90-days.
Secondary	Feasibility - recruitment rate	Ability to recruit 2 patients per site per month.	During active recruitment into the trial, approximately 1 year.