Inhaled Sedation in Critically Ill Patients (IS-CRITIC)

Instituto de Investigación Hospital Universitario La Paz

Status and phase: Enrolling; Phase 4

Conditions: Airway Extubation; Sedation

Treatments: Drug: Isoflurane; Drug: Propofol

Study type: Interventional

Funder types: Other

Identifiers

NCT07000526

HULP6844

2024-518521-14-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The proposal of this study is to compare inhaled sedation with isoflurane administered via the Sedaconda ACD-S system with intravenous sedation with propofol. Patients will be randomized 1:1 to receive either inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous propofol. The primary endpoint is the number of ventilator-free days at 28 days after randomization.

Full description

Justification: Isoflurane has recently emerged as an attractive alternative for intensive care unit (ICU) sedation. Due to their favorable pharmaco-kinetic and dynamic profile, this agent has been progressively introduced into clinical practice. Isoflurane has proven to be non-inferior to propofol in terms of efficacy and safety and it has been suggested that it may facilitate ventilator weaning. However, no differences in length of mechanical ventilation were found. These studies have focused on short sedation durations. In fact, long-term effects and outcomes associated with isoflurane for ICU sedation are not yet fully understood.

Hypothesis: Inhaled sedation with isoflurane administered via the Sedaconda ACD-S system in critically ill patients leads to a shorter duration of mechanical ventilation at 28 days and a reduced length of ICU stay compared to intravenous sedation with propofol.

Main objective: To compare the number of ventilator-free days at day 28 post-randomization between critically ill patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients expected to require more than 48 hours of invasive mechanical ventilation. Key secondary objective: To compare the number of ICU-free days at day 28 post-randomization in both treatment arms. Secondary objectives: To compare time to extubation after sedation withdrawal, efficacy in maintaining a target level of sedation, compare the percentage of patients requiring one or more additional hypnotics, compare the incidence and duration of delirium at day 28, assess mental, cognitive, and quality of life status at 90 days post-hospital discharge between both treatment groups.

Methodology: Phase IV, low-intervention, open-label, multicenter, randomized controlled trial with intention-to-treat analysis including mechanically ventilated patients expected to require a minimum of 48 hours of mechanical ventilation with a RASS score between -3 and -5. Patients will be randomized 1:1 to receive inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous sedation with propofol. A total of 620 patients will be included from a pool of 22 participating centers.

Enrollment: 620 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

- Adult patients receiving mechanical ventilation, with an anticipated duration >48 hours after randomization, and requiring deep sedation (target RASS between -3 and -5).

Exclusion criteria

• Contraindication to isoflurane or propofol
• Allergy to isoflurane or propofol
• Cardiopulmonary arrest
• History of ventricular tachycardia or long QT syndrome
• Tidal volume < 300 mL or PaCO₂ > 50 mmHg at the time of randomization.
• Invasive mechanical ventilation for more than 48 hours at the time of randomization.
• Pregnancy
• Breast feeding
• Acute neurological condition
• ECMO
• ECCO2R
• Active humidification strictly required
• Burns
• Lack of informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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620 participants in 2 patient groups

Study group

Experimental group

Description:

Inhaled sedation with Isoflurane. Initial dose: 3 mL/h. Gradual dose increase until target RASS is achieved. Do not exceed 14 mL/h. Guided by end tidal isoflurane concentration (EtISO), the recommended maximum dose for prolonged use is 1%. Short periods at up to 1.5% may be considered. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added.

Treatment:

Drug: Isoflurane

Control group

Active Comparator group

Description:

Intravenous sedation with propofol (20 mg/mL). Initial dose: 0.5-1 mg/kg/h. Gradual dose increase until target RASS is achieved. Do not exceed 4 mg/kg/h. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added.

Treatment:

Drug: Propofol