Role of Active Deresuscitation After Resuscitation-2

Not Applicable

Completed

• Conditions: Critical Illness; Trauma; Sepsis
• Interventions: Other: Usual care strategy; Other: Conservative fluid and deresuscitation strategy

• Registration Number: NCT03512392
• Lead Sponsor: Belfast Health and Social Care Trust

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.

Study Timeline

• Study First Submitted: 2017-12-05
• Study Start: 2018-04-10
• Study First Submitted QC: 2018-04-19
• Study First Posted: 2018-04-30
• Primary Completion: 2020-01-21
• Study Completion: 2021-07-17
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-14
• Last Update Posted: 2022-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 180

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Usual care	Usual care strategy	Usual care at the discretion of the treating team
Conservative fluid and deresuscitation	Conservative fluid and deresuscitation strategy	* 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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Incidence of reported adverse events	Up to study day 5	Incidence of reported adverse events up to day 5 (intervention period)
Mortality	28 and 180 days	Mortality
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)
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)
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)
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.
Cognitive function	180 days	Cognitive function score (assessed using the Montreal Cognitive Assessment (MoCA-blind) instrument)
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)
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.

Trial Locations

Locations (8)

Northern Health and Social Care Trust; 🇬🇧 Antrim, Northern Ireland, United Kingdom

Belfast City Hospital; 🇬🇧 Belfast, Northern Ireland, United Kingdom

Aneurin Bevan University Health Board; 🇬🇧 Newport, Gwent, United Kingdom

South-Eastern Health and Social Care Trust; 🇬🇧 Dundonald, Northern Ireland, United Kingdom

Royal Victoria Hospital; 🇬🇧 Belfast, Northern Ireland, United Kingdom

Sunderland Royal Hospital; 🇬🇧 Sunderland, Tyne And Wear, United Kingdom

Western Health and Social Care Trust; 🇬🇧 Londonderry, United Kingdom

Manchester University NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom