SEvoflurane for Sedation in ARds

Study Overview
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Brief Summary
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This study evaluates whether a sedation with inhaled sevoflurane will decrease mortality and increase time off the ventilator at 28 days in patients with acute respiratory distress syndrome (ARDS). Half of the patients will receive inhaled sedation with sevoflurane and the other half will receive intravenous sedation with propofol.

Detailed Description
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PRIMARY OBJECTIVE: To assess the efficacy of a sedation with inhaled sevoflurane in improving in reducing mortality and morbidity in patients with moderate-severe ARDS in comparison to a control group receiving intravenous sedation with propofol. PRIMARY HYPOTHESIS: Inhaled sedation with sevoflurane will improve a composite outcome of mortality and time off the ventilator at 28 days, in patients with moderate-severe ARDS. The trial will accrue a maximum of 700 patients. Patients will be recruited from participating intensive care units and randomized to the active (inhaled sevoflurane) or control (intravenous propofol). The overall strategy is to screen and enroll early, every newly intubated, acutely ill or postoperative, patient at each site, using clinically obtained pulse oximetry and blood gases. By providing superior awakening and extubation times, as well as lung-protective effects from anti-inflammatory and protective effects from epithelial injury, inhaled sevoflurane may hasten recovery from lung injury and improve outcomes.

Official Title
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Sevoflurane for Sedation in Acute Respiratory Distress Syndrome: A Multicenter Prospective Randomized Trial

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Inhaled sedation with sevoflurane
* Drug: intravenous sedation with propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Presence for ≤24 hours of all of the following conditions, within one week of a clinical insult or new or worsening respiratory symptoms: PaO2/FiO2 <150 mmHg with positive end-expiratory pressure (PEEP) ≥8 cmH2O (or, if arterial blood gas not available, SpO2/FiO2 that is equivalent to a PaO2/FiO2 <150 mmHg with PEEP ≥8 cmH2O and a confirmatory SpO2/FiO2 between 1-6 hours after the initial SpO2/FiO2 determination) Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present Exclusion Criteria: Absence of affiliation to the French Sociale security Patient under a tutelage measure or placed under judicial protection Continuous sedation with inhaled sevoflurane at enrollment Known pregnancy Currently receiving ECMO therapy Chronic respiratory failure defined as PaCO2 >60 mmHg in the outpatient setting Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing Body mass index >40 kg/m2 Chronic liver disease defined as a Child-Pugh score of 12-15 Expected duration of mechanical ventilation <48 hours Moribund patient, i.e. not expected to survive 24 hours despite intensive care Burns >70% total body surface Previous hypersensitivity or anaphylactic reaction to sevoflurane or cisatracurium 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) Known hypersensitivity to propofol or any of its components Known allergy to eggs, egg products, soybeans, and soy products Suspected or proven intracranial hypertension Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL (as recommended by the manufacturer for the use of the AnaConDa-S (Sedana Medical, Danderyd, Sweden) Enrollment in another interventional ARDS trial with direct impact on sedation and mechanical ventilation Endotracheal ventilation for greater than 120 hours (5 days) Persistent bronchopleural fistula despite chest tube drainage PaO2/FiO2 (if available) >200 mmHg after meeting inclusion criteria and before randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Investigator-initiated, multicenter, prospective, randomized, stratified, parallel-group clinical trial with blinded outcome assessment and concealed allocation of patients with moderate-to-severe ARDS to a strategy of inhaled sedation with sevoflurane or to a strategy of current intravenous sedation practice using propofol.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: inhaled sedation with sevoflurane<br>Inhaled sedation with sevoflurane, as vaporized via the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden) | Drug: Inhaled sedation with sevoflurane<br>* Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden).<br>|
| Active Comparator: intravenous sedation with propofol<br>intravenous sedation with propofol, as already routinely used in participating ICUs | Drug: intravenous sedation with propofol<br>* intravenous sedation with propofol, as already routinely used in participating ICUs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free days through day 28 | Number of days alive and off the ventilator at 28 days, thereby considering death as a competing event | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day survival (Key secondary outcome) |  | Day 90 | 
| All-cause, all-location 28-day mortality (Secondary outcome) |  | Day 28 | 
| All-cause hospital 28-day mortality (Secondary outcome) |  | Day 28 | 
| All-cause, all-location 14-day mortality (Secondary outcome) |  | Day 14 | 
| All-cause, all-location 7-day mortality (Secondary outcome) |  | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, Sedation, Inhaled sevoflurane