Clinical trial NCT06326112: Role of Active Deresuscitation After Resuscitation:
Official title: Role of Active Deresuscitation After Resuscitation: The RADAR-Canada Pilot Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Fluid Overload
Critical Illness
Sepsis
ARDS
Trauma
Keywords: sepsis
acute respiratory distress syndrome
multiple trauma
critical illness
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2024-03-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RADAR-Canada is a parallel group CT in which study participants are randomized in a 1:1 ratio to protocolized deresuscitation or usual care
Primary purpose: TREATMENT

Brief summary: The RADAR-Canada trial is a pilot RCT undertaken to assess the acceptability of, compliance with, and biologic consequences of a deresuscitation protocol designed to expedite the removal of excess interstitial fluid in patients who remain in a positive fluid balance following admission to an intensive care unit (ICU).

Detailed description: Background: Over the course of an acute illness, critically ill patients typically receive substantial volumes of intravenous fluids, administered for resuscitation, maintenance, and as diluents for medications. A positive fluid balance is associated with adverse clinical outcomes. Whether active reversal of a positive fluid balance through fluid restriction and diuresis will improve outcomes is uncertain.

Methods: The Role of Active Deresuscitation After Resuscitation (RADAR) trial is a pilot study to determine the feasibility of a larger trial powered for clinically important outcomes, the acceptability of a deresuscitation protocol, and the impact of a trial on stability of practice patterns. RADAR is an open label pilot trial that will recruit 120 patients from 10 to 12 active sites in Canada. Eligible patients will be 18 years or older, mechanically ventilated \>48 hours but in the ICU for less than five days, and in a calculated positive fluid balance of \> three liters. Patients will be randomized to either usual care or a deresuscitation protocol incorporating a fluid minimization strategy and diuresis.

Results and Discussion: Evidence that recruited patients will be managed according to the trial protocol, with a withdrawal rate of less than 5%, a compliance rate of \>75% and a crossover rate of \<10% will establish the acceptability of the protocol. A mean difference in fluid balance between groups of more than three liters 72 hours after enrolment will establish the feasibility of the protocol. Analyses of clinical effects will be secondary analyses. Survival to day 90 following randomization will be measured, and other clinical measures will provide estimates of rates of key outcomes to inform the design of a definitive, adequately powered trial.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older
2. Mechanically ventilated for \> 48 hours
3. Calculated volume accumulation \> 3 liters since ICU admission or pitting edema in at least two sites (arms, legs, or trunk)
4. Admitted to ICU for ≤ five days
5. Informed consent obtained from patient or alternate decision-maker

Exclusion Criteria:

1. Lack of consent from patient or substitute decision maker or from responsible physician 2. Active bleeding (defined as \> 2 units transfused RBC in past 24 hours) 3. Hemodynamic instability (defined as use of vasopressors \>0.1 µg/kg/minute norepinephrine or equivalent, or increase in vasopressor dose over past 6 hours) 4. Currently receiving dialysis, or plans to initiate dialysis imminently 5. P/F ratio \< 75 6. Subarachnoid hemorrhage 7. Severe traumatic brain injury with admission GCS \<8 8. Diabetic ketoacidosis or hyperosmolar state 9. Acute cardiac failure or cardiogenic shock 10. Suspected or established diabetes insipidus 11. Allergy to furosemide 12. High probability of death within 24 hours

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Primary outcomes:
measure: Efficacy: Mean cumulative fluid balance
timeFrame: 72 hours following randomization
measure: Compliance with deresuscitation protocol
timeFrame: Each 24 hours over first week
measure: Acceptability of protocol
timeFrame: Day 1
Secondary outcomes:
measure: All cause mortality
timeFrame: 90 days following randomization
measure: New onset organ dysfunction
timeFrame: 7 days following randomization
measure: Organ support-free days
timeFrame: 28 days following randomization
Other outcomes:
measure: Inflammatory and renal biomarkers - change from baseline values
timeFrame: 3 days following randomization
Locations:
city: Toronto
country: Canada
facility: Unity Health Toronto
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: John C Marshall, MD
role: PRINCIPAL_INVESTIGATOR
References: