1476O - Haloperidol and lorazepam for agitated delirium in patients with advanced cancer: A multicenter, double-blind, randomized clinical trial (RCT)

Background

Agitated delirium is highly distressing and common in advanced cancer patients. The use of medications is often debated due to mixed evidence. In this double-blind, 4-parallel group RCT, we compared the effect of scheduled haloperidol, lorazepam, combination therapy, and placebo on agitated delirium.

Methods

Delirious adults with advanced cancer admitted to acute palliative care units with persistent agitation despite non-pharmacologic therapies and low-dose haloperidol were randomly assigned to scheduled haloperidol, lorazepam, haloperidol plus lorazepam, or placebo. Rescue medications were identical to scheduled doses except for placebo group, which had lorazepam as rescue. The primary outcome was change in Richmond Agitation Sedation Scale (RASS) score in the first 24 h (range -5 to +4, >0 = hyperactive). Secondary outcomes included rescue medication use, delirium severity, adverse events and survival.

Results

111 patients were enrolled and 75 received the blinded treatments (haloperidol n=16, lorazepam n=20, combination n=19, placebo n=20). RASS score decreased significantly in all groups at 24 h, particularly in the combination and lorazepam groups (Table). In pre-specified intention-to-treat comparison, the lorazepam group had significantly lower RASS than haloperidol (mean difference [95% CI] -2.1 [-3.4, -0.9]; P

Conclusions

Scheduled medications proactively reduced breakthrough agitation compared to placebo. Lorazepam and combination therapy were more effective than haloperidol.

Clinical trial identification

NCT03743649.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Cancer Institute (R01CA225701).

Disclosure

D. Hui: Financial Interests, Personal, Other, Consultant: Eton. All other authors have declared no conflicts of interest.