Acute Respiratory Distress Syndrome
Conditions
Keywords
ARDS, Sedation, Inhaled sevoflurane
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.
Interventions
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden).
DRUGintravenous sedation with propofol
intravenous sedation with propofol, as already routinely used in participating ICUs.
Sponsors
University Hospital, Clermont-Ferrand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
At each participating center, patients will be followed up for primary and secondary endpoints by members of the research staff who will be unaware of the trial group allocation. Information on whether the primary and secondary outcomes occur will be collected and entered into the electronic web-based case report form (eCRF) by trial or clinical trained personal (clinical research associate), blinded to the allocation group, under the supervision of the local principal investigator (PI) or designee who will also be unaware of the trial group allocation. Finally, the independent trial statistician and the members of the data monitoring and safety committee (DMSC) will also remain blinded for the allocation during analysis. However, the observation of differences in serious adverse events between the two groups will allow, for safety reasons may the DMSC deem necessary, to unblind allocation groups.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | 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 |
Countries
France
Contacts
STUDY_CHAIRMatthieu Jabaudon
University Hospital, Clermont-Ferrand
PRINCIPAL_INVESTIGATORRaïko Blondonnet
University Hospital, Clermont-Ferrand
PRINCIPAL_INVESTIGATORJean-Michel Constantin
APHP - La Pitié Salpêtrière
PRINCIPAL_INVESTIGATORAntoine Roquilly
Nantes University Hospital
PRINCIPAL_INVESTIGATORSamir Jaber
CHU Montpellier - Saint-Eloi
PRINCIPAL_INVESTIGATORVirginie Lemiale
APHP - Saint-Louis
PRINCIPAL_INVESTIGATORCarole Ichai
CHU NICE
PRINCIPAL_INVESTIGATORLionel Velly
APHM - La Timone
PRINCIPAL_INVESTIGATORStéphanie Bulyez
CHU Nîmes
PRINCIPAL_INVESTIGATORSigismond Lasocki
University Hospital, Angers
PRINCIPAL_INVESTIGATORJean-Pierre Quenot
CHU Dijon
PRINCIPAL_INVESTIGATORThomas Lebouvier
CHU Rennes
PRINCIPAL_INVESTIGATORFrançois Legay
CH Brieuc
PRINCIPAL_INVESTIGATORArnaud W. Thille
CHU Poitiers
PRINCIPAL_INVESTIGATORAlexandre Lautrette
Centre Jean-Perrin Clermont-Ferrand
PRINCIPAL_INVESTIGATORJulien Pottecher
CHU Strasbourg
PRINCIPAL_INVESTIGATORFranck Verdonk
APHP - Saint-Antoine
PRINCIPAL_INVESTIGATORChristophe Vinsonneau
CH Béthune
PRINCIPAL_INVESTIGATORPierre-Marie Bertrand
CH Cannes
PRINCIPAL_INVESTIGATORMehran Monchi
CH Melun-Sénart
PRINCIPAL_INVESTIGATORJoël Cousson
CHU REIMS
PRINCIPAL_INVESTIGATORJulien Maizel
CHU Amiens
PRINCIPAL_INVESTIGATORErwan L'Her
CHU Brest
PRINCIPAL_INVESTIGATORBelaïd Bouhemad
CHU Dijon
PRINCIPAL_INVESTIGATORBoris Jung
CHU Montpellier - Lapeyronie
PRINCIPAL_INVESTIGATORClaire Dahyot-Fizelier
CHU Poitiers
PRINCIPAL_INVESTIGATORClaire Lhommet
Hopital Diaconesses - La Croix Simon
PRINCIPAL_INVESTIGATORCaroline Varillon
CH Dunkerque
PRINCIPAL_INVESTIGATORArthur Durand
CHU Lille
PRINCIPAL_INVESTIGATORMarc Gainnier
APHM - La Timone
PRINCIPAL_INVESTIGATORFabien Lambiotte
Hospital Valenciennes
PRINCIPAL_INVESTIGATORJulien Lorber
Hospital, Saint Nazaire
PRINCIPAL_INVESTIGATORDelphine Brégeaud
HOSPITAL, SAINTES
PRINCIPAL_INVESTIGATORAziz Berrouba
Hospital Martigues
PRINCIPAL_INVESTIGATORJulio Badie
Hospital Belfort
PRINCIPAL_INVESTIGATORAlexandre Conia
HOSPITAL, CHARTRES
PRINCIPAL_INVESTIGATORFrançois Thouy
University Hospital, Clermont-Ferrand
Outcome results
None listed