Role of Active Deresuscitation After Resuscitation-2

NCT03512392 | Completed DMC

• 1 other identifier: 17057JS-AS
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 8

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.

Conditions

Critical Illness; Sepsis; Trauma

Keywords

fluid therapy; furosemide; diuretics; Injections, Intravenous; Infusions, Intravenous; Spironolactone; Indapamide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Cumulative fluid balance

  Up to the beginning of days 3 and 5, and at ICU discharge (estimated median day 7)

• Incidence of significant protocol violations

  Up to study day 5

• Incidence of reported adverse events

  Up to study day 5

• Change in Sequential Organ Function Assessment scores

  From baseline until day 3 and day 5

• Mortality

  28 and 180 days

Other Outcomes (3)

• Mean regional cerebral oxygen saturation

  72 hours from randomisation

• Minimum regional cerebral oxygen saturation

  72 hours from randomisation

• Regional cerebral hypoxia burden

  72 hours from randomisation

Study Arms (2)

Conservative fluid and deresuscitation

EXPERIMENTAL

* 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

Usual care

ACTIVE COMPARATOR

Usual care at the discretion of the treating team

Other: Usual care strategy

Interventions

Conservative fluid and deresuscitation strategy OTHER

Conservative administration of intravenous fluid and active deresuscitation using diuretics or renal replacement therapy for eligible patients

Conservative fluid and deresuscitation

Usual care strategy OTHER

Usual care at the discretion of the clinical team

Usual care

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead
• Queen's University, Belfast: collaborator
• University of Toronto: collaborator

Study Sites (8)

Aneurin Bevan University Health Board

Newport, Gwent, United Kingdom

Location

Northern Health and Social Care Trust

Antrim, Northern Ireland, United Kingdom

Location

Belfast City Hospital

Belfast, Northern Ireland, BT12 6AB, United Kingdom

Location

Royal Victoria Hospital

Belfast, Northern Ireland, BT12 6BA, United Kingdom

Location

South-Eastern Health and Social Care Trust

Dundonald, Northern Ireland, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, Tyne and Wear, United Kingdom

Location

Western Health and Social Care Trust

Londonderry, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Location

Related 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.

  PMID: 27734109 BACKGROUND

• 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.

  PMID: 34913089 RESULT

MeSH Terms

Conditions

Critical Illness; Sepsis; Wounds and Injuries

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Study Officials

• Jon Silversides, MB BCh

  Belfast Health and Social Care Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Group assignment and early (up to 28 day) data will be locked and unavailable to investigators undertaking 6-month follow up.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, open-label, allocation concealed, pilot trial

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: April 30, 2018
• Study Start: April 10, 2018
• Primary Completion: January 21, 2020
• Study Completion: July 17, 2021
• Last Updated: April 21, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (8)