Inhaled sedation versus intravenous sedation in critically ill patients (IS-CRITIC): protocol for a multicentre, randomised, controlled clinical trial in Spain

Introduction

Intravenous sedatives are widely used in the intensive care unit (ICU) and are part of routine clinical practice. However, these agents and their active metabolites may be associated with adverse events. Volatile anaesthetics have recently emerged as an attractive alternative for ICU sedation, and isoflurane has been approved by regulatory agencies in several European countries for use in critically ill patients. Although isoflurane has been shown to be non-inferior to propofol-based sedation during short-term sedation periods, it remains unclear whether inhaled sedation with isoflurane offers advantages over intravenous sedation in patients requiring prolonged mechanical ventilation and, consequently, prolonged sedation. Methods and analysis: This is a phase IV, low-intervention, open-label, multicentre randomised clinical trial conducted on an intention-to-treat basis. A total of 620 patients will be randomised in a 1:1 ratio to receive either inhaled sedation with isoflurane administered using the Sedaconda ACD-S device or intravenous sedation with propofol. Adult patients expected to require more than 48 hours of mechanical ventilation will be included. The primary outcome is ventilator-free days through day 28 post-randomisation. The key secondary outcome is ICU-free days through day 28 post-randomisation. Patient recruitment began in December 2025 and is expected to conclude in December 2027. Final analysis is planned for 2028. Ethics and dissemination: The study protocol was approved by the ethics committee of Hospital Universitario La Paz, Madrid, Spain (#6844) and the European Medicines Agency on 13 March 2025. Results will be disseminated through peer-reviewed publications and conference presentations. Trial registration number: NCT07000526. This clinical trial is registered in the European Union (EU) Clinical Trials Information System (CTIS), under the EU Clinical Trials Regulation (Regulation 536/2014).