SEvoflurane for Sedation in ARds

Phase 3

Completed

• Conditions: Acute Respiratory Distress Syndrome
• Interventions: Drug: Inhaled sedation with sevoflurane; Drug: intravenous sedation with propofol

• Registration Number: NCT04235608
• Lead Sponsor: University Hospital, Clermont-Ferrand

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-01-14
• Study First Submitted QC: 2020-01-16
• Study First Posted: 2020-01-22
• Study Start: 2020-05-03
• Primary Completion: 2023-10-31
• Status Verified: 2024-06
• Study Completion: 2024-10-02
• Last Update Submitted: 2024-10-21
• Last Update Posted: 2024-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 700

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
inhaled sedation with sevoflurane	Inhaled sedation with sevoflurane	Inhaled sedation with sevoflurane, as vaporized via the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
intravenous sedation with propofol	intravenous sedation with propofol	intravenous sedation with propofol, as already routinely used in participating ICUs

Primary Outcome Measures

Name	Time	Method
Ventilator-free days through day 28	Day 28	Number of days alive and off the ventilator at 28 days, thereby considering death as a competing event

Secondary Outcome Measures

Name	Time	Method
All-cause, all-location 28-day mortality (Secondary outcome)	Day 28
90-day survival (Key secondary outcome)	Day 90
All-cause hospital 28-day mortality (Secondary outcome)	Day 28
All-cause, all-location 7-day mortality (Secondary outcome)	Day 7
All-cause, all-location 14-day mortality (Secondary outcome)	Day 14

Trial Locations

Locations (22)

University Hospital; 🇫🇷 Rennes, France

Hospital Belfort; 🇫🇷 Belfort, France

Cavale Blanche Hospital - University Hospital; 🇫🇷 Brest, France

Hospital; 🇫🇷 Saintes, France

Hospital Chartres; 🇫🇷 Chartres, France

University Hospital,; 🇫🇷 Clermont Ferrand, France

Jean Perrin Comprehensive Cancer Center; 🇫🇷 Clermont-Ferrand, France

Hospital Martigues; 🇫🇷 Martigues, France

Salengro Hospital - University Hospital; 🇫🇷 Lille, France

Timone Hospital - Assistance Publique-Hôpitaux; 🇫🇷 Marseille, France

Lapeyronie Hospital - University Hospital; 🇫🇷 Montpellier, France

Carémeaux Hospital - University Hospita; 🇫🇷 Nîmes, France

Hautepierre Hospital, University Hospitals; 🇫🇷 Strasbourg, France

Hotel Dieu Hospital - University Hospital; 🇫🇷 Nantes, France

Saint-Eloi Hospital - University Hospital; 🇫🇷 Montpellier, France

Pasteur 2 Hospital - University Hospital; 🇫🇷 Nice, France

Diaconesses - La Croix Simon Hospital; 🇫🇷 Paris, France

Hospital Saint-Nazaire; 🇫🇷 Saint-Nazaire, France

Hospital Valenciennes; 🇫🇷 Valenciennes, France

Saint-Louis University Hospital - Assistance Publique-Hôpitaux; 🇫🇷 Paris, France

Saint-Antoine University Hospital - Assistance Publique-Hôpitaux; 🇫🇷 Paris, France

Pitié-Salpêtrière Hospital, - Assistance Publique-Hôpitaux; 🇫🇷 Paris, France