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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Critical Illness, Acute Kidney Injury, Kidney Replacement

Intervention / Treatment
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* Other: Protocol-based fluid management
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Admitted to the ICU 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. Planned initiation of KRT within the following 12 hours or the receipt of KRT for AKI for ≤48 hours Exclusion Criteria: 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 Probable discharge from the ICU within the next 48 hours according to treating physician Severe burn injury (>10% of body surface area) Severe abnormality in serum sodium (>155 or <120 mmol/L) Important ongoing fluid losses are present and/or are expected to require continued maintenance IV fluids uring the next 48 hours The clinical care team believes that the proposed intervention is inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Protocolized fluid removal<br> | Other: Protocol-based fluid management<br>* Fluid removal will be prescribed using a standardized template updated at least once per working day, before noon of each day, by the attending care team. This protocolized prescription will contain three components. Fluid removal will be prescribed using a standardized template updated at least once per working day, before noon of each day, by the attending care team. This protocolized prescription will contain three components. The first component of this prescription will be to define the 24h-fluid balance target either aiming for a negative fluid balance of 2 to 3% body weight (1.4-2.1 liters in a 70 Kg participant) (Option 1) or by aiming to avoid fluid accumulation by targeting a neutral fluid balance within 0.5% of body weight variation (-350 to +350 mL in a 70 Kg participant) (Option 2). The second component is to pre-specify a prescription for fluid removal using KRT. The third component is to prompt a daily re-evaluation of fluid intake by the attending care team.<br>|
| Active Comparator: Usual care<br> | Other: Usual care<br>* The net fluid removal and the rate of net fluid removal will not be protocolized and will be prescribed and adjusted according to the attending care team without any specific guidance. The use of the documents provided for the intervention group will not be permitted in the control arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative fluid balance | The difference between quantifiable fluid intake and output | From randomization to the end of day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: Ability to successfully enroll | Target >30% of fully eligible patients | During screening and enrolment | 
| Feasibility: Protocol adherence | defined as >80% of participants adhering to the allocated treatment for 5 days after enrolment | From randomization to the end of day 5 | 
| Feasibility: Ability to achieve follow-up | Ability to achieve > 95% follow-up regarding all clinical outcomes | From randomization through day 90. | 
| Clinical: Death | Death from any cause | From randomization through day 90. | 
| Clinical: Vasoactive therapy-free days | 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. | From randomization through day 28. | 
| Clinical: Mechanical ventilation-free days | A ventilator-free day will be defined as the receipt of ≥ 2 hours of mechanical ventilation within a 24-hour period. | From randomization through day 28. | 
| Clinical: KRT-free days | An KRT-free day will be defined receiving any KRT modality for ≥ 2 hours within a 24 hours period. | From randomization through day 28. | 
| Clinical: ICU-free days | An ICU-free day will be defined as admission to an ICU for ≥ 2 hours within a 24 hours period. | From randomization through day 90 | 
| Clinical: Hospital-free days | Hospital-free days will be defined as a 24-hour period completely free of an inpatient hospitalization. | From randomization through day 90 | 
| Dependence on KRT | KRT dependence will be defined by the receipt of any form of KRT | within +/- 7 days of the 90-day time point following randomization. | 
| Resource use: cumulative time of continuous KRT | Total cumulative duration in hours | From randomization to the end of day 5 | 
| Resource use: cumulative time of intermittent KRT | Total cumulative duration in hours | From randomization to the end of day 5 | 
| Safety: Maximal vasopressor requirements | Maximal vasopressor requirements as per the vasoactive-inotropic score recorded during each 24-hour period. | From randomization to the end of day 5 | 
| Safety: Severity of illness | Total sequential organ failure assessment (SOFA) score recorded during each 24-hour period. | From randomization to the end of day 5 | 
| Process measures: Target fluid balance as prescribed in the initial fluid balance prescription for the day |  | From randomization to the end of day 5 | 
| 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 | 
| Process measures: Clinical elements used to assess fluid accumulation |  | From randomization to the end of day 5 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid balance management, Ultrafiltration