A2B

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 we want to keep patients less sedated, but it is difficult to get the balance of sedation and comfort right. The purpose of this study is to compare if patients on dexmedetomidine or clonidine come off the ventilator quicker than those just on propofol. We will also see if there was a difference between the groups in the number of people who experienced delirium in ICU, compare how comfortable people were and measure if participants memories of being in ICU differed.

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Chief Investigator: Professor Timothy Walsh

Number and location of participating sites / geographical scope (by region/ country): UK – 40-50 sites

EudraCT number:  2018-001650-98

Funder: NIHR Health Technology Assessment (HTA) Programme. Ref : HTA 16/93/01

Start and End date

Of grant award: April 2018 - July 2024

Of recruitment: July 2018 - October 2023

Current Status: Completed

Protocol publication: BMJ Open 2023;13:e078645. doi: 10.1136/bmjopen-2023-078645   
 

“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”
 

• A2B Publication
• JAMA. doi:10.1001/jama.2025.7200
• Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial

Lay summary of study results

Intensive care (ICU) patients needing support from breathing machines need medications (sedatives and painkillers) to keep them comfortable. There is evidence that keeping people as awake as possible during care helps them recover, but the best way to achieve this is uncertain. This programme of work compared the use of propofol (currently the most widely used sedative) with two drugs called ‘alpha2-agonists’ (dexmedetomidine and clonidine). Some evidence suggests alpha2-agonists have advantages over propofol, by enabling patients to be more awake and comfortable on the breathing machine. They may also decrease confusion (delirium), which is common and distressing during ICU care. However, there are also concerns that these drugs, especially dexmedetomidine, may not be safe for some patients. In a large trial randomising patients equally to receive either mainly propofol or dexmedetomidine or clonidine as their main sedative we did not find a significant difference in the time taken for people to come off the breathing machine. We found no differences in most measures of patient comfort, and more patients experienced agitation with both dexmedetomidine and clonidine. We also found these sedatives caused higher rates of abnormally slow heart rate compared with propofol, which was a concern to medical and nursing staff caring for patients. We did not find any important differences in patient survival or well-being during six months’ follow-up. We also found no evidence that either drug offers better value for money if used as the main sedation agent compared with propofol. Our work suggests we should not use alpha2-agonists as the main sedative for all ICU patients. There is some uncertainty about our findings, because we found issues like clinician experience and pre-existing beliefs and concerns about alpha2-agonists influenced how they were used. We also cannot exclude that they may have advantages in specific patients based on individual clinicians’ judgement.

Co-enrolment Agreements:

Co-enrolment between A2B and the following non-CTIMP studies has been agreed:  ADAPT-Sepsis; A-STOP; BLING III, The Norepinephrine Response Test (NRT) study; REST; FLO-ELA; EFFORT; RADAR-2; GAinS; Cryostat-2, SARIPOC, HOT-ICU, INHALE, ABC Post-ICU, RECOVERY-RS, UK-ROX, MERIT, SCUFFD, T4P, iRehab, PRONTO

Co-enrolment between A2B and the following observational/sampling studies has been agreed:  Appetite; Genomic; Iona; EPICS; ILTIS, Sepsis Immunomics, PARIS, Aspi-Flu, Phind, MOSES, ARDS-Neut, PQIP, CIRCA, KRAKIL, VAMp-Sepsis, Gut-Liver Axis (GLA), ISARIC, PREFIBRILLATE, PIMMS, CandiRes, ENLIST, NOVEL, IMPACCT, SQUEEZE, BioAID, METABOLIC, UNIVERSAL, Barriers and Facilitators, D-RISC-2, LicuID

Sponsor: The University of Edinburgh and Lothian Health Board, ACCORD (ref: AC18022),The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ.  http://accord.scot/

Chief Investigator: Professor Timothy Walsh

Trial Manager: Sîan Irvine, Edinburgh Clinical Trials Unit, Usher Building, The University of Edinburgh, 5‒7 Little France Road, Edinburgh BioQuarter ‒ Gate 3, EDINBURGH EH16 4U  Email: A2B@ed.ac.uk

ECTU Involvement: Trial management /Statistics/ Database and randomisation service.

(UKCRC)