Trial Endpoints

Primary Endpoint:

The primary feasibility endpoint is the difference (95% CI) in the total delivered effluent flow rate per patient between those in the lower and standard CRRT dose-intensity groups. The WISDOM pilot trial will target the detection of a minimum difference of 10 mL/kg/hr in average delivered dose-intensity between the groups.

Secondary Endpoints:

The secondary feasibility endpoints are:

i) enrollment rate, with a target average of ≥ 2 patients/site/month.
ii) proportion of eligible patients consented, with a target of > 50% of fully eligible patients.

iii) time to randomization, with a target of > 75% of eligible patients within 12-hours.
iv) protocol adherence for allocated CRRT dose-intensity, with a target time in-range of >80%.
v) ability to capture delivered CRRT dose-intensity process measures. This is a measure of trial implementation and fidelity, with a target of capture of > 95% of daily CRRT dose-intensity (hourly).
vi) ability to capture clinical endpoints at 90-days, with a target of > 95%.

Biochemical Endpoints:

The secondary biochemical endpoints to assess the tolerability of the intervention are:

i) daily serum sodium, bicarbonate, base excess, strong ion difference (SID) and pH while receiving CRRT, and number (%) days without severe acidemia (pH < 7.25) (excluding day of randomization).
ii) daily serum magnesium, potassium, and phosphate while receiving CRRT, and number (%) of days without hyperkalemia (K+ > 5.5 mmol/L) (excluding day of randomization).

iii) daily serum urea while receiving CRRT, and number (%) of days without serum urea > 35 mmol/L (excluding day of randomization).

Process of Care Endpoints:

The process of care measures to assess the tolerability of the intervention are:

i) daily lowest/highest CRRT dose-intensity delivered for any given hour following randomization.
ii) proportion of hours/day when CRRT dose-intensity is in target range. This is a primary protocol adherence process measure and will provide evidence of between group differences in dose-intensity.

iii) total treatment time/day while receiving CRRT following randomization. This will be defined as time on treatment divided by 24-hours.
iv) total number of hemofilter/circuit replacements during CRRT following randomization.
v) total volume of replacement/dialysate fluid used per day following randomization.
vi) total number and cumulative doses of supplemental electrolytes (Mg+, K+, PO4-, HCO3-), protein and vitamins administered while receiving CRRT.
vii) measure of daily nursing bedside workload, while receiving CRRT following randomization.

Safety Endpoints:

The safety endpoints are:

i) occurrence of trial-related adverse and serious adverse events.
ii) occurrence of trial-related adverse events and serious adverse events leading to discontinuation of the trial intervention.

Tertiary Endpoints:

The WISDOM pilot trial has not been designed to detect differences in patient-centred, kidney-centred or health service-specific outcomes, however, we will measure the following tertiary outcomes: duration of RRT; transition from CRRT to IHD; receipt of RRT at hospital discharge, 30-days and 90-days; RRT-free days at 90-days; ICU mortality; hospital mortality; 90-day mortality; a composite of major adverse kidney events (MAKE) at 30-days and 90-days; delta estimated glomerular filtration rate (baseline to 90-days); daily receipt of non-renal organ support (e.g., invasive and non-invasive mechanical ventilation; vasoactive therapy), ICU length of stay, hospital length of stay and re-hospitalization within 90-days.