Role of Active Deresuscitation After Resuscitation-2 (RADAR-2)

Role of Active Deresuscitation After Resuscitation- 2: a Pilot Randomised Controlled Trial of Conservative Fluid Management Versus Usual Care in Critical Illness

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Critical Illness; Trauma
• Intervention / Treatment: Other: Conservative fluid and deresuscitation strategy; Other: Usual care strategy

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 Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Londonderry, United Kingdom
    • Western Health and Social Care Trust
  • Manchester, United Kingdom
    • Manchester University NHS Foundation Trust
  • Gwent
    • Newport, Gwent, United Kingdom
      • Aneurin Bevan University Health Board
  • Northern Ireland
    • Antrim, Northern Ireland, United Kingdom
      • Northern Health and Social Care Trust
    • Belfast, Northern Ireland, United Kingdom, BT12 6BA
      • Royal Victoria Hospital
    • Belfast, Northern Ireland, United Kingdom, BT12 6AB
      • Belfast City Hospital
    • Dundonald, Northern Ireland, United Kingdom
      • South-Eastern Health and Social Care Trust
  • Tyne And Wear
    • Sunderland, Tyne And Wear, United Kingdom
      • Sunderland Royal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Conservative fluid and deresuscitation; 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	Other: Conservative fluid and deresuscitation strategy; Conservative administration of intravenous fluid and active deresuscitation using diuretics or renal replacement therapy for eligible patients
ACTIVE_COMPARATOR: Usual care; Usual care at the discretion of the treating team	Other: Usual care strategy; Usual care at the discretion of the clinical team

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day 3 fluid balance	Change in fluid balance (mL) between the beginning of study day 2 and the beginning of study day 3.	From beginning of day 2 to the beginning of study day 3.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative fluid balance	Cumulative fluid balance (mL) from ICU admission	Up to the beginning of days 3 and 5, and at ICU discharge (estimated median day 7)
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)	Up to study day 5
Incidence of reported adverse events	Incidence of reported adverse events up to day 5 (intervention period)	Up to study day 5
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.	From baseline until day 3 and day 5
Mortality	Mortality	28 and 180 days
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)	28 days
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)	28 days
Acute kidney injury	Incidence of new acute kidney injury defined as estimated KDIGO Stage 3 (before and after correction for fluid balance)	Up to day 5.
Cognitive function	Cognitive function score (assessed using the Montreal Cognitive Assessment (MoCA-blind) instrument)	180 days
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.	180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean regional cerebral oxygen saturation	Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), mean rScO2 level (%)	72 hours from randomisation
Minimum regional cerebral oxygen saturation	Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), Minimum rScO2 level	72 hours from randomisation
Regional cerebral hypoxia burden	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.	72 hours from randomisation

Collaborators and Investigators

• Sponsor: Belfast Health and Social Care Trust
• Collaborators: University of Toronto; Queen's University, Belfast
• Investigators: Principal Investigator: Jon Silversides, MB BCh, Belfast Health And Social Care Trust

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 10, 2018
• Primary Completion (ACTUAL): January 21, 2020
• Study Completion (ACTUAL): July 17, 2021

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: April 19, 2018
• First Posted (ACTUAL): April 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 21, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: furosemide; diuretics; Spironolactone; Injections, Intravenous; Infusions, Intravenous; Indapamide; fluid therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 17057JS-AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No