Clinical trial NCT05849779: Inhaled Sevoflurane for ARDS Prevention
Official title: Randomized Clinical Trial of Inhaled Sedation With Sevoflurane in Critically Ill Patients at Risk of Developing the Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Keywords: ARDS
Sedation
Inhaled sevoflurane
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2023-05-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated, single-center, prospective, randomized, stratified, parallel-group clinical trial with blinded outcome assessment and concealed allocation of patients at risk of developing the ARDS to a strategy of inhaled sedation with sevoflurane or to a strategy of current intravenous sedation practice.
Primary purpose: TREATMENT

Brief summary: This study focuses on patients who are at risk of developing a serious, life-threatening respiratory disease called Acute Respiratory Distress Syndrome (ARDS), which severely disrupts the function of their lungs.

Preclinical studies have shown that the use of a volatile anesthetic agent such as Sevoflurane could be beneficial in the treatment and prevention of this respiratory condition. By improving gas exchange and attenuating pulmonary inflammation in particular, this agent would make it possible to prevent deterioration or to restore pulmonary function more rapidly.

Half of the patients will receive inhaled sedation with sevoflurane and the other half will receive intravenous sedation already routinely used in participating ICUs (typically propofol, dexmedetomidine or a benzodiazepine, i.e. drugs approved for sedation).

The aim of this study is to assess whether the use of Sevoflurane could be beneficial in the prevention of ARDS.

Detailed description: MAIN OBJECTIVE To assess the efficacy of inhaled sevoflurane, compared to current intravenous sedation practice, for improving PaO2/FiO2 in ICU patients at high risk for ARDS.

HYPOTHESIS The investigators hypothesized that a strategy of inhaled sedation with sevoflurane could be more effective than current intravenous sedation practice at improving pulmonary function during the early days of ICU admission, in patients at risk of ARDS.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. Admitted to participating ICUs with at least one known risk factor for ARDS and a LIPS equals to, or greater than, 4 (Appendix D)105
3. Patient under invasive mechanical ventilation
4. With expected duration of sedation superior or equal to 4 hours
5. Affiliation to the French Sécurité Sociale

Exclusion Criteria:

* Patient under judicial protection, guardianship or supervision, as defined by art L1121-8 of the Public Health Code
* Patient under psychiatric care as defined by art. L1121-6 of the Public Health Code
* Patient deprived of their freedom by judiciary or administrative order
* Known pregnancy
* Presence of ARDS prior to randomization
* Endotracheal ventilation for greater than 24 hours prior to randomization
* Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
* Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL (i.e. height inferior to 134cm for a man and 139cm for a woman)
* Moribund patient, i.e. not expected to survive 24 hours despite intensive care
* Previous hypersensitivity or anaphylactic reaction to sevoflurane or to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine)
* Absolute contra-indications to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine)
* Medical history of malignant hyperthermia
* Long QT syndrome at risk of arrhythmic events
* Medical history of liver disease attributed to previous exposure to a halogenated agent (including sevoflurane)
* Suspected or proven intracranial hypertension
* Enrollment in another interventional trial with direct impact on oxygenation

Primary outcomes:
measure: PaO2/FiO2 ratio
timeFrame: within 5 days from randomization
Secondary outcomes:
measure: Progression to ARDS
timeFrame: within 5 days from randomization
measure: Rate of pneumonia
timeFrame: Presence of pneumonia will be assessed daily until Day 5, and at Day 28 or ICU discharge, whichever comes first.
measure: Ventilator-free days to day 28
timeFrame: 28 days after randomization
measure: Organ failure to day 5
timeFrame: 5 days after randomization
measure: Mortality at day 28
timeFrame: 28 days after randomization
measure: Length of ICU-stay up to 28 days
timeFrame: 28 days after randomization
measure: Physiological measures: Oxygenation
timeFrame: 28 days after randomization
measure: Physiological measures: PaCO2
timeFrame: 28 days after randomization
measure: Physiological measures: pH
timeFrame: 28 days after randomization
measure: Physiological measures: PEEP
timeFrame: 28 days after randomization
measure: Physiological measures: Plateau pressure
timeFrame: 28 days after randomization
measure: Physiological measures: Pneumothorax
timeFrame: 28 days after randomization
measure: Physiological measures: Switch from controlled to pressure-support ventilation
timeFrame: 28 days after randomization
measure: Physiological measures: Airway occlusion pressure
timeFrame: 28 days after randomization
measure: Hemodynamic measures
timeFrame: 28 days after randomization
measure: Physiological measures: Acute kidney injury
timeFrame: 28 days after randomization
measure: Physiological measures: Supraventricular tachycardia
timeFrame: 28 days after randomization
measure: ICU-acquired delirium
timeFrame: 28 days after randomization
measure: Biomarker measurements
timeFrame: from inclusion to 5 days
Other outcomes:
Locations:
city: Clermont-ferrand
country: France
facility: CHU Clermont-Ferrand
state: Not Required For This Country
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Matthieu JABAUDON
role: PRINCIPAL_INVESTIGATOR
References: