Critical Illness, Sepsis, Trauma
Conditions
Keywords
fluid therapy, furosemide, diuretics, Injections, Intravenous, Infusions, Intravenous, Spironolactone, Indapamide
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.
Interventions
OTHERConservative fluid and deresuscitation strategy
Conservative administration of intravenous fluid and active deresuscitation using diuretics or renal replacement therapy for eligible patients
OTHERUsual care strategy
Usual care at the discretion of the clinical team
Sponsors
Queen's University, Belfast
University of Toronto
Belfast Health and Social Care Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Group assignment and early (up to 28 day) data will be locked and unavailable to investigators undertaking 6-month follow up.
Intervention model description
Randomised, open-label, allocation concealed, pilot trial
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Day 3 fluid balance | From beginning of day 2 to the beginning of study day 3. | Change in fluid balance (mL) between the beginning of study day 2 and the beginning of study day 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 28 and 180 days | Mortality |
| Acute kidney injury | Up to day 5. | Incidence of new acute kidney injury defined as estimated KDIGO Stage 3 (before and after correction for fluid balance) |
| Cognitive function | 180 days | Cognitive function score (assessed using the Montreal Cognitive Assessment (MoCA-blind) instrument) |
| Health-related quality of life | 180 days | 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. |
| Cumulative fluid balance | Up to the beginning of days 3 and 5, and at ICU discharge (estimated median day 7) | Cumulative fluid balance (mL) from ICU admission |
| Incidence of significant protocol violations | Up to study day 5 | 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 | Up to study day 5 | Incidence of reported adverse events up to day 5 (intervention period) |
| Change in Sequential Organ Function Assessment scores | From baseline until day 3 and day 5 | 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. |
| Duration of mechanical ventilation | 28 days | 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 | 28 days | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Regional cerebral hypoxia burden | 72 hours from randomisation | 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. |
| Mean regional cerebral oxygen saturation | 72 hours from randomisation | Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), mean rScO2 level (%) |
| Minimum regional cerebral oxygen saturation | 72 hours from randomisation | Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), Minimum rScO2 level |
Countries
United Kingdom
Outcome results
None listed