A phase 2 open-label pilot study of Remimazolam for sedation in critically ill patients

INTRODUCTION: Remimazolam is a novel benzodiazepine with an ultra-short half-life. It is a potentially interesting alternative for sedation in the Intensive Care Unit, but there is limited data regarding its use in critically ill patients. METHODS: Phase 2, investigator-initiated, single-center, non-randomized, open-label study. Patients with an expected duration of sedation ≥ 24 h were eligible and received a maximum 48-h infusion of Remimazolam, with a dose ranging from 0.1 to 1 mg/min. The primary endpoint was a composite of the ability to reach a targeted sedation level without the use of another hypnotic drug and hemodynamic stability (no drop in mean arterial pressure ≤ 65 mmHg and no increase in norepinephrine dose ≥ 50% for more than 1 h), during the first 8 h after start. Secondary endpoints included the monitoring of Adverse Events (AE) and pharmacokinetics. RESULTS: 30 patients were included with a median age of 60 [51-70] years, a SAPS II 38 [30-46], and a mortality rate of 23.3%. Fourteen (46.7%) patients met the primary endpoint. Ten (33.3%) patients received Remimazolam for 48 h and 4 (13.3%) patients received the highest dose. 54 AEs were reported in 23 patients and 11 were classified as Serious AEs in 8 patients. Ten AEs were related to Remimazolam. The pharmacokinetics analysis showed steady plasma levels throughout the infusion and rapid elimination after dosing discontinuation. DISCUSSION: Remimazolam could be useful for sedation in the ICU but deserves further investigation before routine use. TRIAL REGISTRATION: NCT04611425. Registered 2 November 2020.