Role of Active Deresuscitation After Resuscitation:
- Conditions
- Fluid OverloadCritical IllnessARDSTraumaSepsis
- Interventions
- Registration Number
- NCT06326112
- Lead Sponsor
- Unity Health Toronto
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 120
- Age 18 years or older
- Mechanically ventilated for > 48 hours
- Calculated volume accumulation > 3 liters since ICU admission or pitting edema in at least two sites (arms, legs, or trunk)
- Admitted to ICU for ≤ five days
- Informed consent obtained from patient or alternate decision-maker
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active deresuscitation Furosemide Injection * Fluid minimization: clinical and research teams will review all intravenous orders and attempt to reduce fluids to 10-15 ml/hr. * Active deresuscitation: * Administer bolus furosemide 0.5 mg/kg bid or tid * Target daily negative fluid balance as follows: Calculated positive balance: \< 3 liters -600 - -800 ml/24 hours 3-6 liters 0.8 - 1.2 liters/24 hours 6- 10 liters 1.2 - 2.0 liters/24 hours \>10 liters \>2.0 liters/24 hours * If bolus furosemide fails to achieve these goals, results in hypotension or tachycardia, or at the discretion of the attending intensivist, start furosemide infusion titrated on an hourly basis to achieve above goals * If single agent ineffective, consider addition of metolazone Active deresuscitation Metolazone Tablets * Fluid minimization: clinical and research teams will review all intravenous orders and attempt to reduce fluids to 10-15 ml/hr. * Active deresuscitation: * Administer bolus furosemide 0.5 mg/kg bid or tid * Target daily negative fluid balance as follows: Calculated positive balance: \< 3 liters -600 - -800 ml/24 hours 3-6 liters 0.8 - 1.2 liters/24 hours 6- 10 liters 1.2 - 2.0 liters/24 hours \>10 liters \>2.0 liters/24 hours * If bolus furosemide fails to achieve these goals, results in hypotension or tachycardia, or at the discretion of the attending intensivist, start furosemide infusion titrated on an hourly basis to achieve above goals * If single agent ineffective, consider addition of metolazone
- Primary Outcome Measures
Name Time Method Efficacy: Mean cumulative fluid balance 72 hours following randomization Total fluid input (mL) - output (mL) in each group
Compliance with deresuscitation protocol Each 24 hours over first week Daily fluid balance in mL \>10 liters, target \>2.0 liters/24 hours
Acceptability of protocol Day 1 Percentage of eligible patients who consent to randomization
- Secondary Outcome Measures
Name Time Method All cause mortality 90 days following randomization Deaths
New onset organ dysfunction 7 days following randomization Change in aggregate Multiple Organ Dysfunction (MOD) score from baseline, where the range is 0 - 25, and higher values indicate more severe organ dysfunction
Organ support-free days 28 days following randomization Days alive and free from respiratory or hemodynamic support
Trial Locations
- Locations (1)
Unity Health Toronto
🇨🇦Toronto, Ontario, Canada