Fluid OverloadPhase 2RADAR-CanadaNCT06326112
Role of Active Deresuscitation After Resuscitation:
A Phase 2 study testing Furosemide Injection and Metolazone Tablets in people with Fluid Overload and Critical Illness, run by Unity Health Toronto at 1 site in Canada.
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). Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Fluid Overload, Critical Illness, Sepsis
- What is being tested?
- Furosemide Injection and Metolazone Tablets
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2024to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Canada1 site
Unity Health Toronto
Toronto, Ontario, M5B 1W8
John C Marshall, MD, 4168645225, john.marshall@unityhealth.to
About this study
Official title: Role of Active Deresuscitation After Resuscitation: The RADAR-Canada Pilot Clinical Trial
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).
Read the 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
- Being tested
- Furosemide Injection, Metolazone Tablets
- Keywords
- sepsis, acute respiratory distress syndrome, multiple trauma, critical illness
- Medical subject headings
- Edema, Critical Illness, Sepsis, Wounds and Injuries, Respiratory Distress Syndrome, Multiple Trauma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide InjectionDrug
o.5 mg/kg bid or tid IV
Metolazone TabletsDrug
Diuretic as needed
| Study group | Role | What they receive |
|---|---|---|
| Active deresuscitation | Experimental | * 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 Receives: Drug: Furosemide Injection; Drug: Metolazone Tablets |
| Usual care | No intervention | Care at the discretion of the attending team. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: Mean cumulative fluid balance
Total fluid input (mL) - output (mL) in each group
Measured: 72 hours following randomization
Compliance with deresuscitation protocol
Daily fluid balance in mL >10 liters, target >2.0 liters/24 hours
Measured: Each 24 hours over first week
Acceptability of protocol
Percentage of eligible patients who consent to randomization
Measured: Day 1
Secondary outcomes (3)
All cause mortality
Deaths
Measured: 90 days following randomization
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
Measured: 7 days following randomization
Organ support-free days
Days alive and free from respiratory or hemodynamic support
Measured: 28 days following randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start1 May 2024 (estimated)
- Primary completion31 Mar 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fluid OverloadStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, John Marshall, Unity Health Toronto
- Investigators
- John C Marshall, MD, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06326112
- Sponsor's protocol ID
- 4588
- Acronym
- RADAR-Canada
- Status last verified
- Mar 2024
- First submitted
- 26 Feb 2024
- Last updated
- 22 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Active Deresuscitation After Resuscitation: The RADAR-Canada Pilot Clinical Trial
- ClinicalTrials.gov ID
- NCT06326112
- Acronym / sponsor ID
- RADAR-Canada / 4588
- Conditions
- Fluid Overload, Critical Illness, Sepsis, ARDS, Trauma
- Keywords
- sepsis, acute respiratory distress syndrome, multiple trauma, critical illness
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 1 May 2024 (estimated)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 22 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Active deresuscitation | Experimental | Drug: Furosemide Injection, Drug: 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 |
| Usual care | No intervention | –Care at the discretion of the attending team. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Furosemide Injectiono.5 mg/kg bid or tid IV | Drug | Active deresuscitation |
| Metolazone TabletsDiuretic as needed | Drug | Active deresuscitation |
Primary outcome
Efficacy: Mean cumulative fluid balance
Time frame: 72 hours following randomization
Total fluid input (mL) - output (mL) in each group
Compliance with deresuscitation protocol
Time frame: Each 24 hours over first week
Daily fluid balance in mL >10 liters, target >2.0 liters/24 hours
Acceptability of protocol
Time frame: Day 1
Percentage of eligible patients who consent to randomization
3 secondary outcomes
All cause mortality
Time frame: 90 days following randomization
New onset organ dysfunction
Time frame: 7 days following randomization
Organ support-free days
Time frame: 28 days following randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John C Marshall, MD principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Furosemide Injection and Metolazone Tablets in people with Fluid Overload and Critical Illness, run by Unity Health Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laura Romero, RN (416-864-6060, Laura.Romero@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy: Mean cumulative fluid balance (time frame: 72 hours following randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.