INhaled Sedation versus Propofol in REspiratory failure in the Intensive Care Unit (INSPiRE-ICU1): protocol for a randomised, controlled trial

INTRODUCTION: Sedation in mechanically ventilated adults in the intensive care unit (ICU) is commonly achieved with intravenous infusions of propofol, dexmedetomidine or benzodiazepines. Significant limitations associated with each can impact their usage. Inhaled isoflurane has potential benefit for ICU sedation due to its safety record, sedation profile, lack of metabolism and accumulation, and fast wake-up time. Administration in the ICU has historically been restricted by the lack of a safe and effective delivery system for the ICU. The Sedaconda Anaesthetic Conserving Device-S (Sedaconda ACD-S) has enabled the delivery of inhaled volatile anaesthetics for sedation with standard ICU ventilators, but it has not yet been rigorously evaluated in the USA. We aim to evaluate the efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S compared with intravenous propofol for sedation of mechanically ventilated ICU adults in USA hospitals. METHODS AND ANALYSIS: INhaled Sedation versus Propofol in REspiratory failure in the ICU (INSPiRE-ICU1) is a phase 3, multicentre, randomised, controlled, open-label, assessor-blinded trial that aims to enrol 235 critically ill adults in 14 hospitals across the USA. Eligible patients are randomised in a 1.5:1 ratio for a treatment duration of up to 48 (±6) hours or extubation, whichever occurs first, with primary follow-up period of 30 days and additional follow-up to 6 months. Primary outcome is percentage of time at target sedation range. Key secondary outcomes include use of opioids during treatment, spontaneous breathing efforts during treatment, wake-up time at end of treatment and cognitive recovery after treatment. ETHICS AND DISSEMINATION: Trial protocol has been approved by US Food and Drug Administration (FDA) and central (Advarra SSU00208265) or local institutional review boards ((IRB), Cleveland Clinic IRB FWA 00005367, Tufts HS IRB 20221969, Houston Methodist IRB PRO00035247, Mayo Clinic IRB Mod22-001084-08, University of Chicago IRB21-1917-AM011 and Intermountain IRB 033175). Results will be presented at scientific conferences, submitted for publication, and provided to the FDA. TRIAL REGISTRATION NUMBER: NCT05312385.