Role of Active Deresuscitation After Resuscitation:

Sepsis Clinical Trial

— RADAR-Canada  

Official title:

Role of Active Deresuscitation After Resuscitation: The RADAR-Canada Pilot Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06326112
• Other study ID #: 4588
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Unity Health Toronto
• Contact: Laura Romero, RN
• Phone: 416-864-6060
• Email: Laura.Romero[@]unityhealth.to
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: June 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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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Related Conditions & MeSH terms

• ARDS
• Critical Illness
• Fluid Overload
• Sepsis
• Trauma

Intervention

Drug:
• Furosemide Injection
o.5 mg/kg bid or tid IV
• Metolazone Tablets
Diuretic as needed

Locations

Country	Name	City	State
Canada	Unity Health Toronto	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Unity Health Toronto	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Inflammatory and renal biomarkers - change from baseline values	including, but not limited to IL-6, sTNFr1, ICAM, HCO3-, protein C, CRP) or markers of AKI (including, but not limited to N-GAL, KIM-1, TIMP2-IGFBP-7, cystatin C	3 days following randomization
Primary	Efficacy: Mean cumulative fluid balance	Total fluid input (mL) - output (mL) in each group	72 hours following randomization
Primary	Compliance with deresuscitation protocol	Daily fluid balance in mL >10 liters, target >2.0 liters/24 hours	Each 24 hours over first week
Primary	Acceptability of protocol	Percentage of eligible patients who consent to randomization	Day 1
Secondary	All cause mortality	Deaths	90 days following randomization
Secondary	New onset organ dysfunction	Change in aggregate Multiple Organ Dysfunction (MOD) score from baseline, where the range is 0 - 25, and higher values indicate more severe organ dysfunction	7 days following randomization
Secondary	Organ support-free days	Days alive and free from respiratory or hemodynamic support	28 days following randomization