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

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.

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.

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.

Remimazolam could be useful for sedation in the ICU but deserves further investigation before routine use.

NCT04611425. Registered 2 November 2020.