Alpha-2 agonists for sedation (A2B Trial)
Research type
Research Study
Full title
Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): A randomised, parallel-group, allocation concealed, controlled, open, phase 3 pragmatic clinical and cost- effectiveness trial with internal pilot
IRAS ID
243640
Contact name
Tim Walsh
Contact email
Sponsor organisation
University of Edinburgh and NHS Lothian
Eudract number
2018-001650-98
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Summary of Research
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.For sedation, most ICUs use a drug called 'propofol' that is good at reducing anxiety and making people sleepy. There are two other drugs used less often called 'alpha-2 agonists' that have both sedative and pain-killing actions. The two drugs are called clonidine and dexmedetomidine ('dex').
We 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. We also want to know how safe they are and if they can improve important outcomes during ICU stay and during recovery. We also want to know if they are value for money.
Our trial will include 1737 patients needing to be on a ventilator for at least 2 days. Patients will be allocated to receive dexmedetomidine or clonidine or to continue on propofol. All patients will receive extra pain relief if needed. We will 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 the ICU differed.
Patients who were in the trial will be followed up for 180 days because we want to compare if there were differences in the after-effects of being ill between the groups. We will ask patients to complete questionnaires at 30, 90 and 180 days.
Summary of 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.REC name
Scotland A: Adults with Incapacity only
REC reference
18/SS/0085
Date of REC Opinion
21 Aug 2018
REC opinion
Further Information Favourable Opinion