Inhaled Sevoflurane for ARDS Prevention

NCT05849779 | Recruiting Phase 3 DMC

• 1 other identifier: IPA trial (AOI 2019 JABAUDON)
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

ARDS; Sedation; Inhaled sevoflurane

Outcome Measures

Primary Outcomes (1)

• PaO2/FiO2 ratio

  longitudinal evolution in the PaO2/FiO2 ratio

  within 5 days from randomization

Secondary Outcomes (19)

• Progression to ARDS

  within 5 days from randomization

• Rate of pneumonia

  Presence of pneumonia will be assessed daily until Day 5, and at Day 28 or ICU discharge, whichever comes first.

• Ventilator-free days to day 28

  28 days after randomization

• Organ failure to day 5

  5 days after randomization

• Mortality at day 28

  28 days after randomization

Study Arms (2)

Inhaled sedation with sevoflurane

EXPERIMENTAL

Sevoflurane as vaporized via the Anesthesia Conserving Device (Sedaconda-ACD-S, Sedana Medical, Danderyd, Sweden).

Drug: Inhaled sedation with sevoflurane

Intravenous sedation

ACTIVE COMPARATOR

The investigators will not mandate the sedative type, but rather encourage the use of sedatives that are already routinely used in participating ICUs (typically a benzodiazepine, propofol, or dexmedetomidine, i.e. drugs approved for sedation).

Drug: Intravenous sedation (current practice)

Interventions

Inhaled sedation with sevoflurane DRUG

In both arms, the management of sedation will be conducted in the broader picture of ICU patient care, as per current standard practice in participating ICUs, and following the current guidelines for Pain, Agitation, Delirium, Immobility, and Sleep Disruption (PADIS) published in 2018 by the Society of Critical Care Medicine. Among many recommendations, this will include the monitoring and titration of both sedation and analgesia using validated scores such as the Richmond Agitation-Sedation Scale (RASS) for sedation. As a result of the current recommendations, the level, dose, and duration of sedation will vary among patients and will be decided by the treating clinicians. The choice of the analgesic drug(s) will be as per the treating clinicians. Other aspects of critical care will adhere to standard care, including the use of the "Checklist for Lung Injury Prevention" (CLIP).

Also known as: Experimental

Inhaled sedation with sevoflurane

Intravenous sedation (current practice) DRUG

In both arms, the management of sedation will be conducted in the broader picture of ICU patient care, as per current standard practice in participating ICUs, and following the current guidelines for Pain, Agitation, Delirium, Immobility, and Sleep Disruption (PADIS) published in 2018 by the Society of Critical Care Medicine. Among many recommendations, this will include the monitoring and titration of both sedation and analgesia using validated scores such as the Richmond Agitation-Sedation Scale (RASS) for sedation. As a result of the current recommendations, the level, dose, and duration of sedation will vary among patients and will be decided by the treating clinicians. The choice of the analgesic drug(s) will be as per the treating clinicians. Other aspects of critical care will adhere to standard care, including the use of the "Checklist for Lung Injury Prevention" (CLIP).

Also known as: Control

Intravenous sedation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• 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
• Patient under invasive mechanical ventilation
• With expected duration of sedation superior or equal to 4 hours
• Affiliation to the French Sécurité Sociale

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, Not Required For This Country, 63000, France

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Sevoflurane

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons

Study Officials

• Matthieu JABAUDON

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

+33473754963; llaclautre_perrier@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 9, 2023
• Study Start: July 24, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: July 29, 2024

Record last verified: 2024-07

Locations

FR (1)