Proactive Prescription-based Fluid Management vs Usual Care in Critically Ill Patients on Kidney Replacement Therapy

Not Applicable

Recruiting

• Conditions: Acute Kidney Injury; Kidney Replacement; Critical Illness
• Interventions: Other: Protocol-based fluid management; Other: Usual care

• Registration Number: NCT05473143
• Lead Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Brief Summary

A pilot randomized clinical trial comparing a protocol-based fluid management strategy to usual care in critically ill patients receiving kidney replacement therapy. The fluid management protocol is intended to achieve neutral or negative daily fluid balance by both preventing and treating fluid accumulation.

Detailed Description

Severe acute kidney injury (AKI) in the intensive care unit (ICU) is almost uniformly complicated by fluid accumulation, thus making fluid removal a central component of the renal replacement therapy (KRT) prescription. Whereas the achievement and maintenance of euvolemia are critical objectives in the care of critically ill patients with severe AKI, there remain important knowledge gaps in our ability to effectively and safely deliver ultrafiltration. Multisystemic congestion resulting from fluid accumulation is believed to mediate adverse outcomes in this population and the timely use of mechanical fluid removal may improve prognosis. However, fluid removal may be associated with hemodynamic instability during KRT which may precipitate complications. The optimal fluid management strategy is currently unknown.

The study is a pilot randomized clinical trial comparing a protocol-based fluid management strategy with usual care in critically ill patients receiving KRT. The fluid management protocol is intended to achieve neutral or negative daily fluid balance by both preventing and treating fluid accumulation. The protocol was designed to provide a standardized framework to prescribe fluid removal while allowing the attending care team to modify treatment targets according to their clinical evaluation.

The primary objective of this trial is to determine whether the intervention results in a difference in cumulative fluid balance from randomization to 5 days. Feasibility will be documented including the ability to enroll the target population, protocol adherence, and the capacity to achieve follow-up through 90 days. Secondary outcomes will also include short-term patient outcomes, safety outcomes, and health resource utilization related to KRT delivery.

Study Timeline

• Study First Submitted: 2022-07-15
• Study First Submitted QC: 2022-07-22
• Study First Posted: 2022-07-25
• Study Start: 2023-04-03
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-19
• Primary Completion: 2026-01-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Age ≥ 18 years
2. Admitted to the ICU
3. AKI during current hospitalization defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria(1) as any of the following: Increase in serum creatinine by 27 µmol/L or more within any 48-hour window, or an increase in serum creatinine to 1.5 times baseline or more within the last 7 days, or a urine output less than 0.5 mL/kg/h for 6 hours.
4. Planned initiation of KRT within the following 12 hours or the receipt of KRT for AKI for ≤48 hours

Exclusion Criteria

1. Lack of commitment to maintain kidney, pharmacologic or respiratory support at the time of screening, or probable transition to comfort care within 48 hours according to the treating physician
2. Probable discharge from the ICU within the next 48 hours according to treating physician
3. Severe burn injury (>10% of body surface area)
4. Severe abnormality in serum sodium (>155 or <120 mmol/L)
5. Important ongoing fluid losses are present and/or are expected to require continued maintenance IV fluids uring the next 48 hours
6. The clinical care team believes that the proposed intervention is inappropriate.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Protocolized fluid removal	Protocol-based fluid management	-
Usual care	Usual care	-

Primary Outcome Measures

Name	Time	Method
Cumulative fluid balance	From randomization to the end of day 5	The difference between quantifiable fluid intake and output

Secondary Outcome Measures

Name	Time	Method
Clinical: Death	From randomization through day 90.	Death from any cause
Clinical: KRT-free days	From randomization through day 28.	An KRT-free day will be defined receiving any KRT modality for ≥ 2 hours within a 24 hours period.
Process measures: Target fluid balance as prescribed in the initial fluid balance prescription for the day	From randomization to the end of day 5
Feasibility: Ability to achieve follow-up	From randomization through day 90.	Ability to achieve \> 95% follow-up regarding all clinical outcomes
Clinical: Vasoactive therapy-free days	From randomization through day 28.	A vasoactive-free day will be defined as ≥ 2 hours of receipt of any vasoactive therapy provided by continuous infusion within a 24 hour period. Vasoactive therapy include norepinephrine, vasopressin, phenylephrine, epinephrine, dopamine \>5mcg/kg/min, and angiotensin II.
Clinical: Hospital-free days	From randomization through day 90	Hospital-free days will be defined as a 24-hour period completely free of an inpatient hospitalization.
Safety: Maximal vasopressor requirements	From randomization to the end of day 5	Maximal vasopressor requirements as per the vasoactive-inotropic score recorded during each 24-hour period.
Clinical: Mechanical ventilation-free days	From randomization through day 28.	A ventilator-free day will be defined as the receipt of ≥ 2 hours of mechanical ventilation within a 24-hour period.
Clinical: ICU-free days	From randomization through day 90	An ICU-free day will be defined as admission to an ICU for ≥ 2 hours within a 24 hours period.
Dependence on KRT	within +/- 7 days of the 90-day time point following randomization.	KRT dependence will be defined by the receipt of any form of KRT
Resource use: cumulative time of continuous KRT	From randomization to the end of day 5	Total cumulative duration in hours
Process measures: Proportion of time in which a neutral fluid balance target is selected by the clinical care team	From randomization to the end of day 5
Feasibility: Ability to successfully enroll	During screening and enrolment	Target \>30% of fully eligible patients
Feasibility: Protocol adherence	From randomization to the end of day 5	defined as \>80% of participants adhering to the allocated treatment for 5 days after enrolment
Process measures: The difference between the original target and the fluid balance achieved at the end of each 24-hour period	From randomization to the end of day 5
Resource use: cumulative time of intermittent KRT	From randomization to the end of day 5	Total cumulative duration in hours
Safety: Severity of illness	From randomization to the end of day 5	Total sequential organ failure assessment (SOFA) score recorded during each 24-hour period.
Process measures: Clinical elements used to assess fluid accumulation	From randomization to the end of day 5

Trial Locations

Locations (1)

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada