Role of Active Deresuscitation After Resuscitation-2

Sepsis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03512392
• Other study ID #: 17057JS-AS
• Status: Completed
• Phase: N/A
• Start date: April 10, 2018
• Est. completion date: July 17, 2021

Study information

• Verified date: April 2022
• Source: Belfast Health and Social Care Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: July 17, 2021
• Est. primary completion date: January 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Sepsis
• Trauma

Intervention

Other:
• Conservative fluid and deresuscitation strategy
Conservative administration of intravenous fluid and active deresuscitation using diuretics or renal replacement therapy for eligible patients
• Usual care strategy
Usual care at the discretion of the clinical team

Locations

Country	Name	City	State
United Kingdom	Northern Health and Social Care Trust	Antrim	Northern Ireland
United Kingdom	Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	Royal Victoria Hospital	Belfast	Northern Ireland
United Kingdom	South-Eastern Health and Social Care Trust	Dundonald	Northern Ireland
United Kingdom	Western Health and Social Care Trust	Londonderry
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	Aneurin Bevan University Health Board	Newport	Gwent
United Kingdom	Sunderland Royal Hospital	Sunderland	Tyne And Wear

Sponsors (3)

Lead Sponsor	Collaborator
Belfast Health and Social Care Trust	Queen's University, Belfast, University of Toronto

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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. Review. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean regional cerebral oxygen saturation	Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), mean rScO2 level (%)	72 hours from randomisation
Other	Minimum regional cerebral oxygen saturation	Near infra-red spectroscopic measurement of regional cerebral oxygen saturation), Minimum rScO2 level	72 hours from randomisation
Other	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
Primary	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	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)
Secondary	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
Secondary	Incidence of reported adverse events	Incidence of reported adverse events up to day 5 (intervention period)	Up to study day 5
Secondary	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
Secondary	Mortality	Mortality	28 and 180 days
Secondary	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
Secondary	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
Secondary	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.
Secondary	Cognitive function	Cognitive function score (assessed using the Montreal Cognitive Assessment (MoCA-blind) instrument)	180 days
Secondary	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