Clinical trial NCT03512392: Role of Active Deresuscitation After Resuscitation-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
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Sepsis
Trauma
Keywords: fluid therapy
furosemide
diuretics
Injections, Intravenous
Infusions, Intravenous
Spironolactone
Indapamide
Lead sponsor: Belfast Health and Social Care Trust
Sponsor class: OTHER
Collaborators: name: Queen's University, Belfast
name: University of Toronto
First posted: 2018-04-30
Enrollment: 180
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, open-label, allocation concealed, pilot trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Invasive mechanical ventilation
2. Treating ICU doctor expects patient to require treatment in an ICU beyond the next calendar day
3. Between 24 and 48 hours from ICU admission at the time of randomisation

Exclusion Criteria:

1. Age \< 16 years
2. Body weight \<40kg (measured or estimated)
3. Diabetic ketoacidosis or Hyperosmolar hyperglycaemic state
4. Non-traumatic subarachnoid haemorrhage
5. Acute cardiac failure or cardiogenic shock
6. End-stage renal failure (on dialysis)
7. Known to be pregnant
8. Suspected or proven active diabetes insipidus (DDAVP within 24 hours)
9. Not expected to survive for 72 hours
10. Active 'Do not attempt resuscitation' order
11. Refusal of consent
12. Inability of personal consultee to understand written or verbal information and for whom no interpreter is available
13. Known allergy to one or more of the study drugs
14. Inability to measure fluid balance

Primary outcomes:
measure: Day 3 fluid balance
timeFrame: From beginning of day 2 to the beginning of study day 3.
Secondary outcomes:
measure: Cumulative fluid balance
timeFrame: Up to the beginning of days 3 and 5, and at ICU discharge (estimated median day 7)
measure: Incidence of significant protocol violations
timeFrame: Up to study day 5
measure: Incidence of reported adverse events
timeFrame: Up to study day 5
measure: Change in Sequential Organ Function Assessment scores
timeFrame: From baseline until day 3 and day 5
measure: Mortality
timeFrame: 28 and 180 days
measure: Duration of mechanical ventilation
timeFrame: 28 days
measure: Length of ICU stay
timeFrame: 28 days
measure: Acute kidney injury
timeFrame: Up to day 5.
measure: Cognitive function
timeFrame: 180 days
measure: Health-related quality of life
timeFrame: 180 days
Other outcomes:
measure: Mean regional cerebral oxygen saturation
timeFrame: 72 hours from randomisation
measure: Minimum regional cerebral oxygen saturation
timeFrame: 72 hours from randomisation
measure: Regional cerebral hypoxia burden
timeFrame: 72 hours from randomisation
Locations:
city: Newport
country: United Kingdom
facility: Aneurin Bevan University Health Board
state: Gwent
city: Antrim
country: United Kingdom
facility: Northern Health and Social Care Trust
state: Northern Ireland
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
state: Northern Ireland
city: Dundonald
country: United Kingdom
facility: South-Eastern Health and Social Care Trust
state: Northern Ireland
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: Tyne And Wear
city: Londonderry
country: United Kingdom
facility: Western Health and Social Care Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
affiliation: Belfast Health and Social Care Trust
name: Jon Silversides, MB BCh
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.