Back to resultsRole of Active Deresuscitation After Resuscitation-2 (RADAR-2)
Primary Purpose
Critical Illness, Sepsis, Trauma
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Conservative fluid and deresuscitation strategy
Usual care strategy
Sponsored by
About this trial
This is an interventional treatment trial for Critical Illness focused on measuring fluid therapy, furosemide, diuretics, Injections, Intravenous, Infusions, Intravenous, Spironolactone, Indapamide
Eligibility Criteria
Inclusion Criteria:
- Invasive mechanical ventilation
- Treating ICU doctor expects patient to require treatment in an ICU beyond the next calendar day
- Between 24 and 48 hours from ICU admission at the time of randomisation
Exclusion Criteria:
- Age < 16 years
- Body weight <40kg (measured or estimated)
- Diabetic ketoacidosis or Hyperosmolar hyperglycaemic state
- Non-traumatic subarachnoid haemorrhage
- Acute cardiac failure or cardiogenic shock
- End-stage renal failure (on dialysis)
- Known to be pregnant
- Suspected or proven active diabetes insipidus (DDAVP within 24 hours)
- Not expected to survive for 72 hours
- Active 'Do not attempt resuscitation' order
- Refusal of consent
- Inability of personal consultee to understand written or verbal information and for whom no interpreter is available
- Known allergy to one or more of the study drugs
- Inability to measure fluid balance
Sites / Locations
- Aneurin Bevan University Health Board
- Northern Health and Social Care Trust
- Belfast City Hospital
- Royal Victoria Hospital
- South-Eastern Health and Social Care Trust
- Sunderland Royal Hospital
- Western Health and Social Care Trust
- Manchester University NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Conservative fluid and deresuscitation
Usual care
Arm Description
Fluid restriction (avoidance of maintenance intravenous fluid and minimisation of drug diluent volumes) Daily assessment of eligibility for deresuscitation for 3 days (eligible if oedema in more than 1 site and cumulative fluid balance > 2 litres) Deresuscitation to target negative daily fluid balance of 1 to 3 litres: 5mg Indapamide daily (enteral) 100mg Spironolactone daily (enteral) 0.5mg/kg furosemide once (intravenous, max 40mg) 2.5-20mg/hr furosemide infusion titrated to effect OR continuous renal replacement therapy with fluid removal
Usual care at the discretion of the treating team
Outcomes
Primary Outcome Measures
Day 3 fluid balance
Change in fluid balance (mL) between the beginning of study day 2 and the beginning of study day 3.
Secondary Outcome Measures
Cumulative fluid balance
Cumulative fluid balance (mL) from ICU admission
Incidence of significant protocol violations
Incidence of significant protocol violations (total number of patients, per site, and by nature of protocol violation) up to day 5 (intervention period)
Incidence of reported adverse events
Incidence of reported adverse events up to day 5 (intervention period)
Change in Sequential Organ Function Assessment scores
Change in Sequential Organ Function Assessment scores from baseline, overall (0-24) and 6 individual organ sub scores (respiratory, cardiovascular, neurological, coagulation, renal and liver, each scored 0-4 which are added to give a total score). Higher values represent more deranged physiology and predict mortality for critically ill patients.
Mortality
Mortality
Duration of mechanical ventilation
Duration of mechanical ventilation in survivors and non-survivors (number of days or part thereof from initiation of mechanical ventilatory support until unassisted breathing)
Length of ICU stay
Length of ICU stay (number of days or part thereof from admission to an ICU or being under the care of a critical care team or consultant until ICU discharge)
Acute kidney injury
Incidence of new acute kidney injury defined as estimated KDIGO Stage 3 (before and after correction for fluid balance)
Cognitive function
Cognitive function score (assessed using the Montreal Cognitive Assessment (MoCA-blind) instrument)
Health-related quality of life
Health-related quality of life (HR-QoL) (assessed using absolute values of a telephone-administered EQ-5D (EuroQoL 5 Dimension Scale) questionnaire). This has 5 domains: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, each of which are scored 1-5, with 1 being best and 5 being worst health. Each domain is reported separately. A total score is generated and is indexed to population reference values for that country (in this case UK) according to the time of data collection. It is therefore not possible to pre-specify a range for the indexed score.
Full Information
NCT ID
NCT03512392
First Posted
December 5, 2017
Last Updated
April 14, 2022
Sponsor
Belfast Health and Social Care Trust
Collaborators
Queen's University, Belfast, University of Toronto
1. Study Identification
Unique Protocol Identification Number
NCT03512392
Brief Title
Role of Active Deresuscitation After Resuscitation-2
Acronym
RADAR-2
Official Title
Role of Active Deresuscitation After Resuscitation- 2: a Pilot Randomised Controlled Trial of Conservative Fluid Management Versus Usual Care in Critical Illness
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
January 21, 2020 (Actual)
Study Completion Date
July 17, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Belfast Health and Social Care Trust
Collaborators
Queen's University, Belfast, University of Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RADAR-2 will be a randomised, open-label, allocation concealed, pilot trial of conservative fluid administration and deresuscitation compared with usual care in patients who are critically ill.
Detailed Description
The optimal approach to fluid balance in critically ill patients is uncertain. A recent systematic review found low quality evidence in favour of a conservative fluid or deresuscitative approach (active removal of accumulated fluid using diuretics and/or renal replacement therapy) compared with a liberal strategy or usual care. The RADAR-2 pilot randomised trial will compare conservative fluid and deresuscitation with usual care in patients who are mechanically ventilated in an intensive care unit. The main hypothesis is that in critically ill patients, a post-resuscitation fluid strategy comprising conservative fluid administration and active deresuscitation reduces net fluid balance, is safe and improves clinical outcomes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness, Sepsis, Trauma
Keywords
fluid therapy, furosemide, diuretics, Injections, Intravenous, Infusions, Intravenous, Spironolactone, Indapamide
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomised, open-label, allocation concealed, pilot trial
Masking
None (Open Label)
Masking Description
Group assignment and early (up to 28 day) data will be locked and unavailable to investigators undertaking 6-month follow up.
Allocation
Randomized
Enrollment
180 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Conservative fluid and deresuscitation
Arm Type
Experimental
Arm Description
Fluid restriction (avoidance of maintenance intravenous fluid and minimisation of drug diluent volumes)
Daily assessment of eligibility for deresuscitation for 3 days (eligible if oedema in more than 1 site and cumulative fluid balance > 2 litres)
Deresuscitation to target negative daily fluid balance of 1 to 3 litres:
5mg Indapamide daily (enteral) 100mg Spironolactone daily (enteral) 0.5mg/kg furosemide once (intravenous, max 40mg) 2.5-20mg/hr furosemide infusion titrated to effect OR continuous renal replacement therapy with fluid removal
Arm Title
Usual care
Arm Type
Active Comparator
Arm Description
Usual care at the discretion of the treating team
Intervention Type
Other
Intervention Name(s)
Conservative fluid and deresuscitation strategy
Intervention Description
Conservative administration of intravenous fluid and active deresuscitation using diuretics or renal replacement therapy for eligible patients
Intervention Type
Other
Intervention Name(s)
Usual care strategy
Intervention Description
Usual care at the discretion of the clinical team
Primary Outcome Measure Information:
Title
Day 3 fluid balance
Description
Change in fluid balance (mL) between the beginning of study day 2 and the beginning of study day 3.
Time Frame
From beginning of day 2 to the beginning of study day 3.
Secondary Outcome Measure Information:
Title
Cumulative fluid balance
Description
Cumulative fluid balance (mL) from ICU admission
Time Frame
Up to the beginning of days 3 and 5, and at ICU discharge (estimated median day 7)
Title
Incidence of significant protocol violations
Description
Incidence of significant protocol violations (total number of patients, per site, and by nature of protocol violation) up to day 5 (intervention period)
Time Frame
Up to study day 5
Title
Incidence of reported adverse events
Description
Incidence of reported adverse events up to day 5 (intervention period)
Time Frame
Up to study day 5
Title
Change in Sequential Organ Function Assessment scores
Description
Change in Sequential Organ Function Assessment scores from baseline, overall (0-24) and 6 individual organ sub scores (respiratory, cardiovascular, neurological, coagulation, renal and liver, each scored 0-4 which are added to give a total score). Higher values represent more deranged physiology and predict mortality for critically ill patients.
Time Frame
From baseline until day 3 and day 5
Title
Mortality
Description
Mortality
Time Frame
28 and 180 days
Title
Duration of mechanical ventilation
Description
Duration of mechanical ventilation in survivors and non-survivors (number of days or part thereof from initiation of mechanical ventilatory support until unassisted breathing)
Time Frame
28 days
Title
Length of ICU stay
Description
Length of ICU stay (number of days or part thereof from admission to an ICU or being under the care of a critical care team or consultant until ICU discharge)
Time Frame
28 days
Title
Acute kidney injury
Description
Incidence of new acute kidney injury defined as estimated KDIGO Stage 3 (before and after correction for fluid balance)
Time Frame
Up to day 5.
Title
Cognitive function
Description
Cognitive function score (assessed using the Montreal Cognitive Assessment (MoCA-blind) instrument)
Time Frame
180 days
Title
Health-related quality of life
Description
Health-related quality of life (HR-QoL) (assessed using absolute values of a telephone-administered EQ-5D (EuroQoL 5 Dimension Scale) questionnaire). This has 5 domains: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, each of which are scored 1-5, with 1 being best and 5 being worst health. Each domain is reported separately. A total score is generated and is indexed to population reference values for that country (in this case UK) according to the time of data collection. It is therefore not possible to pre-specify a range for the indexed score.
Time Frame
180 days
Other Pre-specified Outcome Measures:
Title
Mean regional cerebral oxygen saturation
Description
Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), mean rScO2 level (%)
Time Frame
72 hours from randomisation
Title
Minimum regional cerebral oxygen saturation
Description
Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), Minimum rScO2 level
Time Frame
72 hours from randomisation
Title
Regional cerebral hypoxia burden
Description
Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), proportion of time spent with rScO2 below thresholds of 50%, 65%, and 75% as a proportion of the time for which cerebral oxygenation is measured, expressed as a percentage.
Time Frame
72 hours from randomisation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Invasive mechanical ventilation
Treating ICU doctor expects patient to require treatment in an ICU beyond the next calendar day
Between 24 and 48 hours from ICU admission at the time of randomisation
Exclusion Criteria:
Age < 16 years
Body weight <40kg (measured or estimated)
Diabetic ketoacidosis or Hyperosmolar hyperglycaemic state
Non-traumatic subarachnoid haemorrhage
Acute cardiac failure or cardiogenic shock
End-stage renal failure (on dialysis)
Known to be pregnant
Suspected or proven active diabetes insipidus (DDAVP within 24 hours)
Not expected to survive for 72 hours
Active 'Do not attempt resuscitation' order
Refusal of consent
Inability of personal consultee to understand written or verbal information and for whom no interpreter is available
Known allergy to one or more of the study drugs
Inability to measure fluid balance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jon Silversides, MB BCh
Organizational Affiliation
Belfast Health and Social Care Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aneurin Bevan University Health Board
City
Newport
State/Province
Gwent
Country
United Kingdom
Facility Name
Northern Health and Social Care Trust
City
Antrim
State/Province
Northern Ireland
Country
United Kingdom
Facility Name
Belfast City Hospital
City
Belfast
State/Province
Northern Ireland
ZIP/Postal Code
BT12 6AB
Country
United Kingdom
Facility Name
Royal Victoria Hospital
City
Belfast
State/Province
Northern Ireland
ZIP/Postal Code
BT12 6BA
Country
United Kingdom
Facility Name
South-Eastern Health and Social Care Trust
City
Dundonald
State/Province
Northern Ireland
Country
United Kingdom
Facility Name
Sunderland Royal Hospital
City
Sunderland
State/Province
Tyne And Wear
Country
United Kingdom
Facility Name
Western Health and Social Care Trust
City
Londonderry
Country
United Kingdom
Facility Name
Manchester University NHS Foundation Trust
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27734109
Citation
Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. 2017 Feb;43(2):155-170. doi: 10.1007/s00134-016-4573-3. Epub 2016 Oct 12.
Results Reference
background
PubMed Identifier
34913089
Citation
Silversides JA, McMullan R, Emerson LM, Bradbury I, Bannard-Smith J, Szakmany T, Trinder J, Rostron AJ, Johnston P, Ferguson AJ, Boyle AJ, Blackwood B, Marshall JC, McAuley DF. Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial. Intensive Care Med. 2022 Feb;48(2):190-200. doi: 10.1007/s00134-021-06596-8. Epub 2021 Dec 16. Erratum In: Intensive Care Med. 2023 Aug 29;:
Results Reference
result
Learn more about this trial
Role of Active Deresuscitation After Resuscitation-2
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