Alpha 2 Agonists for Sedation to Produce Better Outcomes From Critical Illness (A2B Trial)
A2B
5 other identifiers
interventional
1,437
1 country
38
Brief Summary
Many patients in intensive care (ICU) need help to breathe on a breathing machine and need pain killers and sedatives to keep them comfortable and pain free. However, keeping patients too deeply sedated can make their ICU stay longer, can cause ICU confusion (delirium) and afterwards may cause distressing memories. Ideally patients should be kept less sedated, but it is difficult to get the balance of sedation and comfort right. The investigators want to know whether starting an alpha2-agonist drug early in ICU can help keep patients more lightly sedated but still comfortable, and whether patients spend less time on the ventilator. The investigators also want to know how safe they are and if they can improve important outcomes during ICU stay and during recovery. The investigators also want to know if they are value for money.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2018
Longer than P75 for phase_3
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 21, 2018
CompletedFirst Posted
Study publicly available on registry
August 31, 2018
CompletedStudy Start
First participant enrolled
December 10, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 14, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2024
CompletedOctober 3, 2024
October 1, 2024
5 years
August 21, 2018
October 1, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to first successful extubation post-randomisation (hours).
How many hours are participants on the study ventilated for?
Ventilation status will be recorded twice daily from the date of randomisation until the date of documented successful extubation, or 180 days, whichever comes first.
Secondary Outcomes (24)
Length of ICU stay
ICU status will be recorded daily from the date of randomisation until the date of ICU discharge, or 180 days, whichever comes first.
Delirium prior to successful extubation
Delirium will be assessed twice daily during ICU stay using the Confusion-Agitation method for ICU (CAM-ICU). Delirium will be assessed from the date of randomisation until the date of ICU discharge, or 28 days, whichever comes first.
Duration of Delirium during ICU stay
Delirium will be assessed twice daily during ICU stay using the Confusion-Agitation method for ICU (CAM-ICU). Delirium will be assessed from the date of randomisation until the date of ICU discharge, or 28 days, whichever comes first.
Sedation quality as measured by Richmond Agitation and Sedation Scale (RASS)
Sedation quality will be assessed 4 hourly during the period of ventilation from the date of randomisation until the participant is successfully extubated, or 28 days, whichever comes first.
Sedation quality as measured by Sedation Quality Assessment Tool (SQAT)
Sedation quality will be assessed daily during the period of ventilation from the date of randomisation until the participant is successfully extubated, or 28 days, whichever comes first.
- +19 more secondary outcomes
Study Arms (3)
Dexmedetomidine Group
EXPERIMENTALFor dexmedetomidine, the regimen will follow the manufacturer's guidance and regimens used in previous trials. Dexmedetomidine will be up and down titrated against sedation targets set by clinical staff and reviewed at regular intervals, and documented at least daily. No loading dose will be administered. The starting dose will be 0.7 µg.kg-1.hour-1 titrated to a maximum dose 1.4 µg.kg-1 hour-1. Lower starting doses will be used at clinical discretion for patients with cardiovascular instability.
Clonidine Group
EXPERIMENTALFor clonidine, the regimen is designed to be equipotent with dexmedetomidine based on known pharmacokinetics and pharmacodynamics. The chosen regimen is similar to that currently used in many UK ICUs as part of routine 'off label' practice. Clonidine will be up and down titrated against sedation targets set by clinical staff and reviewed at regular intervals, and at least daily. No loading dose will be administered. The starting dose will be 1.0µg.kg-1.hour-1 titrated to a maximum dose of 2 µg.kg-1.hour-1. Lower starting doses will be used at clinical discretion for patients with cardiovascular instability.
Usual Care (Propofol) Group
ACTIVE COMPARATORUsual Care Group : Patients will continue to receive intravenous propofol according to usual current care . The sedation targets, weaning, and sedation discontinuation procedures will follow the same clinical targets as for the clonidine and dexmedetomidine groups.
Interventions
Patients will commence intravenous infusion of open-label study drug according to a weight-based dose regimen as early as possible post-randomisation, and within a maximum of two hours. Bedside clinical staff will transition patients to achieve sedation with the allocated α2-agonist agent as quickly as clinically feasible and safe, to replicate the way these drugs would be used in routine practice. Additional opiate will be used for analgesia using clinical judgement. Once established, additional propofol will only be used when the maximum α2-agonist dose is reached or because cardiovascular or other side-effects limit dose escalation.
Patients will commence intravenous infusion of open-label study drug according to a weight-based dose regimen as early as possible post-randomisation, and within a maximum of two hours. Bedside clinical staff will transition patients to achieve sedation with the allocated α2-agonist agent as quickly as clinically feasible and safe, to replicate the way these drugs would be used in routine practice. Additional opiate will be used for analgesia using clinical judgement. Once established, additional propofol will only be used when the maximum α2-agonist dose is reached or because cardiovascular or other side-effects limit dose escalation.
Patients will continue to receive intravenous propofol according to current usual care.
Eligibility Criteria
You may qualify if:
- Patient requiring mechanical ventilation (MV) in an ICU
- Aged 18 or over
- Within 48 hours of first episode of mechanical ventilation in ICU
- Requiring sedation with propofol
- Expected to require a total of 48 hours of MV or more in ICU
- Expected to require a further 24 hours of MV or more at the time of randomisation in the opinion of the responsible clinician
You may not qualify if:
- Acute brain injury (traumatic brain injury; intracranial haemorrhage; ischaemic brain injury from stroke or hypoperfusion)
- Post-cardiac arrest (where there is clinical concern about hypoxic brain injury)
- Status epilepticus
- Continuous therapeutic neuromuscular paralysis at the time of screening or randomisation
- Guillain-Barre Syndrome
- Myasthenia gravis
- Home ventilation
- Fulminant hepatic failure
- Patient not expected to survive 24 hours by responsible clinician
- Decision to provide only palliative or end-of-life care
- Pregnancy
- Known allergy to one of the study drugs
- Untreated second or third degree heart block
- Transferred from another Intensive Care Unit in which MV occurred for \>6 hours
- Prisoners
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Edinburghlead
- West Hertfordshire Hospitals NHS Trustcollaborator
- Queen's University, Belfastcollaborator
- The University of Queenslandcollaborator
- University Hospital of Walescollaborator
- Edinburgh Napier Universitycollaborator
- King's College Londoncollaborator
- University of Warwickcollaborator
- University of Manchestercollaborator
- Royal Surrey County Hospital NHS Foundation Trustcollaborator
- University College, Londoncollaborator
- NHS Lothiancollaborator
- Imperial College Londoncollaborator
- University of Cambridgecollaborator
Study Sites (38)
Belfast Health & Social Care Trust
Belfast, United Kingdom
South Eastern Health and Social Trust
Belfast, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Blackpool Teaching Hospitals NHS Foundation Trust
Blackpool, United Kingdom
North Bristol NHS Trust
Bristol, United Kingdom
University Hospitals Bristol NHS Foundation Trust
Bristol, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom
Cardiff and Vale University Health Board
Cardiff, United Kingdom
Countess of Chester Hospital NHS Foundation Trust
Chester, United Kingdom
The Dudley Group NHS Foundation Trust
Dudley, United Kingdom
NHS Dumfries and Galloway
Dumfries, United Kingdom
NHS Lothian
Edinburgh, United Kingdom
Medway NHS Foundation Trust
Gillingham, United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, United Kingdom
Harrogate and District NHS Trust
Harrogate, United Kingdom
Wye Valley NHS Trust
Hereford, United Kingdom
The Queen Elizabeth Hospital Kings Lynn NHS Foundation Trust
Kings Lynn, United Kingdom
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
University Hospitals of Leicester
Leicester, United Kingdom
Lewisham and Greenwich NHS Trust
Lewisham, United Kingdom
Aintree University Hospital Foundation Trust
Liverpool, United Kingdom
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool, United Kingdom
Guys and St Thomas NHS Foundation Trust
London, United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom
St George's University Hospitals NHS Foundation Trust
London, United Kingdom
The Royal Marsden NHS Foundation Trust
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Manchester University Foundation Trust
Manchester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle, United Kingdom
Aneurin Bevan University Health Board
Newport, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Oxford University Hospitals NHS Foundation Trust.
Oxford, United Kingdom
Poole Hospitals NHS Foundation Trust
Poole, United Kingdom
University Hospital Southampton NHSFT
Southampton, United Kingdom
North Tees and Hartlepool NHS Foundation Trust
Stockton-on-Tees, United Kingdom
Taunton and Somerset NHS Foundation Trust
Taunton, United Kingdom
West Hertfordshire Hospitals NHS Trust
Watford, United Kingdom
Related Publications (4)
Emerson LM, Blackwood B, Kydonaki K, McKenzie C, Walsh TS, Aitken LM. The experiences of bedside nurses delivering an intensive care sedation study: A process evaluation within the A2B trial. J Intensive Care Soc. 2025 Nov 6:17511437251381951. doi: 10.1177/17511437251381951. Online ahead of print.
PMID: 41220595DERIVEDWalsh TS, Parker RA, Aitken LM, McKenzie CA, Emerson L, Boyd J, Macdonald A, Beveridge G, Giddings A, Hope D, Irvine S, Tuck S, Lone NI, Kydonaki K, Norrie J, Brealey D, Antcliffe D, Reay M, Williams A, Bewley J, Creagh-Brown B, McAuley DF, Dark P, Wise MP, Gordon AC, Perkins GD, Reade MC, Blackwood B, MacLullich A, Glen R, Page VJ, Weir CJ; A2B Trial Investigators. Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial. JAMA. 2025 Jul 1;334(1):32-45. doi: 10.1001/jama.2025.7200.
PMID: 40388916DERIVEDAitken LM, Emerson LM, Kydonaki K, Blackwood B, Creagh-Brown B, Lone NI, McKenzie CA, Reade MC, Weir CJ, Wise MP, Walsh TS. Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial. BMJ Open. 2024 Apr 5;14(4):e081637. doi: 10.1136/bmjopen-2023-081637.
PMID: 38580355DERIVEDWalsh TS, Aitken LM, McKenzie CA, Boyd J, Macdonald A, Giddings A, Hope D, Norrie J, Weir C, Parker RA, Lone NI, Emerson L, Kydonaki K, Creagh-Brown B, Morris S, McAuley DF, Dark P, Wise MP, Gordon AC, Perkins G, Reade M, Blackwood B, MacLullich A, Glen R, Page VJ. Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): protocol for a multicentre phase 3 pragmatic clinical and cost-effectiveness randomised trial in the UK. BMJ Open. 2023 Dec 10;13(12):e078645. doi: 10.1136/bmjopen-2023-078645.
PMID: 38072483DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy Walsh, MBChB MD MSc
University of Edinburgh
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 21, 2018
First Posted
August 31, 2018
Study Start
December 10, 2018
Primary Completion
December 14, 2023
Study Completion
July 31, 2024
Last Updated
October 3, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Currently unknown
- Access Criteria
- Currently unspecified
The final trial dataset will be held by the University of Edinburgh on a secure password protected drive. Co-investigators will have the right to access the final data set for the purpose of additional analyses that are consistent with the consent provided by participants. Similarly, any external party can approach the co-investigators to request access to the trial data. In all cases, access to the trial dataset will require approval by a majority of the members of the trial management group and the sponsor (or its delegated representative).