The Effect of Guanfacine on Delirium in Surgical and Trauma ICU Patients: A Pilot Randomized Clinical Trial

OBJECTIVES: To evaluate the feasibility of conducting a randomized controlled trial investigating guanfacine for ICU delirium, including assessment of recruitment, retention, protocol adherence, and data completeness, while estimating treatment effects to inform future trial design. DESIGN: Single-center, randomized, double-blind, placebo-controlled pilot trial conducted from November 2020 to February 2023. SETTING: Surgical and Trauma ICUs at the University of Alabama at Birmingham Hospital. PATIENTS: One hundred critically ill adults with Confusion Assessment Method-ICU-confirmed delirium randomized 1:1 to guanfacine or placebo. INTERVENTIONS: Patients received 2 mg guanfacine or matching placebo nightly for up to 14 days, or until ICU discharge or delirium resolution. MEASUREMENTS AND MAIN RESULTS: Primary feasibility outcomes included protocol adherence (target ≥ 90%), retention (target ≥ 80%), recruitment rate (target ≥ 2 patients/mo), and data completeness (target ≥ 95%). Most feasibility targets were achieved: protocol adherence was 100%, retention was 100%, and data completeness was 100%. Recruitment was significantly impacted by COVID-19 pandemic disruptions, achieving 0.9 patients/wk during active recruitment periods.For clinical outcomes, in unadjusted analyses, median delirium and coma-free days were higher with guanfacine than placebo (2 [interquartile range [IQR], 0-6] vs. 1 [IQR, 0-4]; p = 0.02); however, this association was not statistically significant after adjustment for prespecified baseline covariates. ICU and hospital length of stay and duration of mechanical ventilation did not differ significantly between groups. No hemodynamic differences or safety concerns were observed. CONCLUSIONS: This pilot study successfully supports feasibility for a definitive trial, with excellent protocol adherence, adequate retention, and preliminary signals that warrant further evaluation. Although adjusted analyses were not statistically significant, the observed unadjusted difference in delirium and coma-free days and favorable safety profile support progression to a multicenter trial informed by these pilot estimates.