Role of Active Deresuscitation After Resuscitation:

NCT ID: NCT06326112

Last Updated: 2024-03-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2025-06-30

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.

Conditions

Fluid Overload; Critical Illness; Sepsis; ARDS; Trauma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Active deresuscitation

• 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

Group Type: EXPERIMENTAL

Furosemide Injection

Intervention Type: DRUG

o.5 mg/kg bid or tid IV

Metolazone Tablets

Intervention Type: DRUG

Diuretic as needed

Usual care

Care at the discretion of the attending team.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Furosemide Injection

o.5 mg/kg bid or tid IV

Intervention Type: DRUG

Metolazone Tablets

Diuretic as needed

Intervention Type: DRUG

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

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

John Marshall

Professor of Surgery and Critical Care Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John C Marshall, MD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

Unity Health Toronto

Toronto, Ontario, Canada

Countries

Canada

Central Contacts

Laura Romero, RN

Role: CONTACT

Laura.Romero@unityhealth.to

416-864-6060

Michael Sklar, MD

Role: CONTACT

Michael.Sklar@unityhealth.to

416-864-6060

Facility Contacts

John C Marshall, MD

Role: primary

john.marshall@unityhealth.to

4168645225

Other Identifiers

4588

Identifier Type: -

Identifier Source: org_study_id