Role of Active Deresuscitation After Resuscitation: (RADAR-Canada)

Unity Health Toronto

Status and phase: Not yet enrolling; Phase 2

Conditions: Trauma; Critical Illness; ARDS; Fluid Overload; Sepsis

Treatments: Drug: Furosemide Injection; Drug: Metolazone Tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT06326112

4588

Details and patient eligibility

About

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).

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 2 patient groups

Active deresuscitation

Experimental group

Description:

* 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

Treatment:

Drug: Furosemide Injection

Drug: Metolazone Tablets

Usual care

No Intervention group

Description:

Care at the discretion of the attending team.