Haloperidol vs. placebo for the treatment of delirium in ICU patients: a pre-planned, secondary Bayesian analysis of the AID–ICU trial

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Purpose
The AID–ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID–ICU trial results.

Methods
We used adjusted Bayesian linear and logistic regression models with weakly informative priors to analyse all primary and secondary outcomes reported up to day 90, and with sensitivity analyses using other priors. The probabilities for any benefit/harm, clinically important benefit/harm, and no clinically important differences with haloperidol treatment according to pre-defined thresholds are presented for all outcomes.

Results
The mean difference for days alive and out of hospital to day 90 (primary outcome) was 2.9 days (95% credible interval (CrI) − 1.1 to 6.9) with probabilities of 92% for any benefit and 82% for clinically important benefit. The risk difference for mortality was − 6.8 percentage points (95% CrI − 12.8 to − 0.8) with probabilities of 99% for any benefit and 94% for clinically important benefit. The adjusted risk difference for serious adverse reactions was 0.3 percentage points (95% CrI − 1.3 to 1.9) with 98% probability of no clinically important difference. Results were consistent across sensitivity analyses using different priors, with more than 83% probability of benefit and less than 17% probability of harm with haloperidol treatment.

Conclusions
We found high probabilities of benefits and low probabilities of harm with haloperidol treatment compared with placebo in acutely admitted, adult ICU patients with delirium for the primary and most secondary outcomes.
OriginalsprogEngelsk
TidsskriftIntensive Care Medicine
Vol/bind49
Sider (fra-til)411–420
Antal sider10
ISSN0342-4642
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The Department of Intensive Care at Zealand University Hospital, Køge (NCAR, LMP, OM) has received funding for the AID–ICU trial from Innovations Fund Denmark, The Regional Medicines Fund, Zealand Region Research fund, Grosserer L.F. Foghts Fond and Hindsgavl Intensiv Symposium. The funding had no influence on the trial. The department conducts contract research for AM-Pharma, which is unrelated to this work. The Department of Intensive Care at Rigshospitalet (AP, MOC, AG) has received funding for other projects unrelated to this work from Sygeforsikringen “danmark”, The Novo Nordisk Foundation, Pfizer, and, Fresenius Kabi, and conducts contract research for AM-Pharma. The Department of Anaesthesiology and Intensive Care at Copenhagen University Hospital-North Zealand (MB) has received funding for other projects unrelated to this work from Sygeforsikring “danmark”, The Novo Nordisk Foundation, and conducted contract research for AM-Pharma and Inotrem. MB received consulting fees from AM-Pharma.

Funding Information:
This study was funded by Regional Medicines Fund (R124-2651), Innovationsfonden (4108-00011B), Hindsgavl Intensiv Symposium, Fogts Foundation and Zealand Region Research Fund.

Publisher Copyright:
© 2023, Springer-Verlag GmbH Germany, part of Springer Nature.

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