Sevoflurane for Sedation in Acute Respiratory Distress Syndrome: A Multicenter Prospective Randomized Trial
Overview
- Phase
- Phase 3
- Intervention
- intravenous sedation with propofol
- Conditions
- Acute Respiratory Distress Syndrome
- Sponsor
- University Hospital, Clermont-Ferrand
- Enrollment
- 700
- Locations
- 34
- Primary Endpoint
- Ventilator-free days through day 28
- Status
- Completed
- Last Updated
- 11 days ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
intravenous sedation with propofol
intravenous sedation with propofol, as already routinely used in participating ICUs
Intervention: intravenous sedation with propofol
inhaled sedation with sevoflurane
Inhaled sedation with sevoflurane, as vaporized via the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
Intervention: Inhaled sedation with sevoflurane
Outcomes
Primary Outcomes
Ventilator-free days through day 28
Time Frame: Day 28
Number of days alive and off the ventilator at 28 days, thereby considering death as a competing event
Secondary Outcomes
- 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)