Clinical trial NCT07000526: Inhaled Sedation in Critically Ill Patients
Official title: Inhaled Sedation in Critically Ill Patients: a Multicentre Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Sedation
Airway Extubation
Keywords: Inhaled sedation
Mechanical ventilation
Delirium
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2025-06-03
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ventilator-free days at day 28 from randomization
timeFrame: From 48 hs after randomization until day 28
Secondary outcomes:
measure: Key secondary objective: ICU-free days at day 28 post-randomization
timeFrame: From 48 hs after randomization until day 28
measure: Time to extubation
timeFrame: From 48 hs after randomization until day 28
measure: Administration of rescue sedation
timeFrame: From 48 hs after randomization until day 28
measure: Sedation efficacy
timeFrame: From 48 hs after randomization until extubation or day 28
measure: Number of Participants With Delirium
timeFrame: From 48 hs after randomization until extubation or day 28
measure: Mortality
timeFrame: From randomization to day 60
measure: Number of Participants With Psychological disorders
timeFrame: at 90 days of hospital discharge
measure: Number of Participants With Cognitive Disorders
timeFrame: at 90 days of hospital discharge
measure: Number of Participants With Treatment-Related Adverse Events
timeFrame: From randomization to day 28
Other outcomes:
Locations:
city: Orihuela
country: Spain
facility: Hospital Vega Baja
state: Alicante
city: Arrecife
country: Spain
facility: Hospital Universitario Doctor José Molina Orosa
state: Lanzarote-Canary Islands
city: Albacete
country: Spain
facility: Hospital Universitario de Albacete
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Corporacio Sanitaria Parc Taulí
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Universitario Valle de Hebron
city: Cartagena
country: Spain
facility: Hospital General Universitario Santa Lucía
city: Lérida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Univeritario Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Universitario de Getafe
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Rey Juan Carlos
city: Murcia
country: Spain
facility: Hospital Reina Sofía
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Tarragona
country: Spain
facility: Hospital Universitario Joan XXIII
city: Toledo
country: Spain
facility: Hospital Universitario de Toledo
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
Study officials:
affiliation: Hospital Universitario La Paz. IdiPAZ
name: José M. Añón, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: