Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial

Walsh, 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

doi:10.1001/jama.2025.7200

ICU sedation, delirium & recovery

Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial

JAMAPublished 1 Jul 2025Randomised controlled trial

An erratum to this article was published (JAMA, 6 Jan 2026 ↗)

Read the original article ↗PubMed

Cite

Authors' conclusion

In critically ill patients, neither dexmedetomidine nor clonidine was superior to propofol in reducing time to successful extubation.

Study context

Population: Adults within 48 hours of starting mechanical ventilation, receiving propofol plus an opioid, expected to require mechanical ventilation ≥48 hours, 41 intensive care unit (ICUs) in the UKanalysis population
Participants: 1,404 adults

Comparison: Dexmedetomidine- or clonidine-based sedation vs propofol-based sedation
Dexmedetomidinen = 457
Clonidinen = 476
Propofoln = 471reference
Primary endpoint: Time from randomization to successful extubation

Methodological detailspragmatic, open-label, multicentre (41 ICUs)

Pragmatic
Open-label
Multicentre (41 ICUs)

Primary result

As reported in the abstract

Dexmedetomidine136median · 95% CI 117–150 · hours

Clonidine146median · 95% CI 124–168 · hours

Propofol162median · 95% CI 136–170 · hours

Each group vs propofolSubdistribution hazard ratio (95% CI)P value

Dexmedetomidine

1.09(0.96–1.25)

P = 0.20

Clonidine

1.05(0.95–1.17)

P = 0.34

Secondary outcomes

Outcome	← Lower risk vs propofol ←→ Higher risk vs propofol →	Estimate
AgitationDexmedetomidine vs Propofol	0.512	RR 1.54 (95% CI 1.21–1.97)
AgitationClonidine vs Propofol	0.512	RR 1.55 (95% CI 1.22–1.97)
Mortality · 180 daysDexmedetomidine vs Propofol	0.512	HR 0.98 (95% CI 0.77–1.24)
Mortality · 180 daysClonidine vs Propofol	0.512	HR 1.04 (95% CI 0.82–1.31)
	0.512Ratio (log scale)

Predefined subgroups (age, sepsis status, median SOFA score, median delirium risk score)

No interactions

Safety

Outcome	← Lower risk vs propofol ←→ Higher risk vs propofol →	RR (95% CI)
Severe bradycardia (heart rate <50/min)Dexmedetomidine vs Propofol	0.512	1.62 (1.36–1.93)
Severe bradycardia (heart rate <50/min)Clonidine vs Propofol	0.512	1.58 (1.33–1.88)
	0.512Relative risk (log scale)

Original publication

Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial. JAMA. Published 1 July 2025. doi:10.1001/jama.2025.7200

Read the original article ↗

Composed by AI from the published abstract and checked against it. How Briefs are made →