Acute Respiratory Distress SyndromePhase 3IPANCT05849779
Inhaled Sevoflurane for ARDS Prevention
A Phase 3 study testing Inhaled sedation with sevoflurane and Intravenous sedation (current practice) in people with Acute Respiratory Distress Syndrome, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Inhaled sedation with sevoflurane and Intravenous sedation (current practice)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- 24 Jul 2023to 31 Jul 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
- Enrollment in another interventional trial with direct impact on oxygenation
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU Clermont-Ferrand
Clermont-Ferrand, Not Required For This Country, 63000
Dominique Morand, +33684894678, dmorand@chu-clermontferrand.fr
About this study
Official title: Randomized Clinical Trial of Inhaled Sedation With Sevoflurane in Critically Ill Patients at Risk of Developing the Acute Respiratory Distress Syndrome
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.
Read more
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.
Read the detailed description
MAIN OBJECTIVE To assess the efficacy of inhaled sevoflurane, compared to current intravenous sedation practice, for improving PaO2/FiO2 in ICU patients at high risk for ARDS.
HYPOTHESIS The investigators hypothesized that a strategy of inhaled sedation with sevoflurane could be more effective than current intravenous sedation practice at improving pulmonary function during the early days of ICU admission, in patients at risk of ARDS.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Inhaled sedation with sevoflurane, Intravenous sedation (current practice)
- Keywords
- ARDS, Sedation, Inhaled sevoflurane
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled sedation with sevofluraneDrug
Also called Experimental
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).
Intravenous sedation (current practice)Drug
Also called Control
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).
| Study group | Role | What they receive |
|---|---|---|
| Inhaled sedation with sevoflurane | Experimental | Sevoflurane as vaporized via the Anesthesia Conserving Device (Sedaconda-ACD-S, Sedana Medical, Danderyd, Sweden). Receives: 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). Receives: Drug: Intravenous sedation (current practice) |
What is being measured
The primary outcome is the main question the study is designed to answer.
PaO2/FiO2 ratio
longitudinal evolution in the PaO2/FiO2 ratio
Measured: within 5 days from randomization
Secondary outcomes (19)
Progression to ARDS
Progression to ARDS will be assessed according to the Berlin criteria, including chest radiographs
Measured: within 5 days from randomization
Rate of pneumonia
Pneumonia will be defined according to the 3 following criteria:
- Two chest radiographs showing signs of pneumonia, or one in absence of cardiomyopathy or underlying pulmonary condition.
- One item among: body temperature ≥38.3°C without evident cause, leukocytes <4000/mm3 or ≥12000/mm3
- Two items among: purulent secretions, cough or dyspnea, increased need for oxygen supplementation or ventilatory assistance.
Measured: 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
Ventilator free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 27 or dies prior to day 28, VFDs will be zero.
Measured: 28 days after randomization
Organ failure to day 5
Organ failure is defined as present when the most abnormal vital signs or clinically available lab value meets the definition of clinically significant organ failure according to SOFA scores. Patients will be followed daily from randomization to day 5 for development of organ failures.
Measured: 5 days after randomization
Mortality at day 28
The occurrence of death in the ICU will be recorded until day 28.
Measured: 28 days after randomization
Length of ICU-stay up to 28 days
The total number of days from admission to ICU discharge will be recorded until day 28
Measured: 28 days after randomization
Physiological measures: Oxygenation
- Oxygenation Index on study days 1-5
Measured: 28 days after randomization
Physiological measures: PaCO2
- PaCO2 on study days 1-5
Measured: 28 days after randomization
Physiological measures: pH
- Arterial pH on study days 1-5
Measured: 28 days after randomization
Physiological measures: PEEP
- Level of PEEP (and static auto-PEEP in patients under controlled ventilation) on study days 1-5
Measured: 28 days after randomization
Physiological measures: Plateau pressure
- Plateau pressure, static compliance of the respiratory system on study day 1-5
Measured: 28 days after randomization
Physiological measures: Pneumothorax
- Development of pneumothorax through day 28
Measured: 28 days after randomization
Physiological measures: Switch from controlled to pressure-support ventilation
- Time to switching from controlled to pressure-support ventilation through day 5
Measured: 28 days after randomization
Physiological measures: Airway occlusion pressure
- Airway occlusion pressure at 0.1 s (P0.1), an index of respiratory drive, on the day the patient is switched to pressure-support ventilation if within 5 days since randomization
Measured: 28 days after randomization
Hemodynamic measures
- Hemodynamic measures (mean arterial pressure, dose of infused norepinephrine or other vasopressor, serum lactate level) on study days 1-5
Measured: 28 days after randomization
Physiological measures: Acute kidney injury
- KDIGO criteria for acute kidney injury 24 through day 5
Measured: 28 days after randomization
Physiological measures: Supraventricular tachycardia
- Supraventricular tachycardia (SVT) or new onset atrial fibrillation through day 5
Measured: 28 days after randomization
ICU-acquired delirium
The Confusion Assessment Method for the ICU (CAM-ICU, Appendix C )97 will be assessed daily from study entry to study day 28, death or ICU discharge, whichever comes first.
Measured: 28 days after randomization
Biomarker measurements
Plasma samples will be collected from indwelling catheters (when available) at study entry and on days 1, 2, 3, 4, 5 in order to assemble a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane in patients with ARDS.
The investigators will also collect whole blood samples at study entry and on day 2 for future studies of macrophage activation profiles and RNA and DNA studies.
Measured: from inclusion to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start24 Jul 2023
- Primary completion31 May 2026 (estimated)
- Study completion31 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthieu JABAUDON, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05849779
- Sponsor's protocol ID
- IPA trial (AOI 2019 JABAUDON)
- Acronym
- IPA
- Status last verified
- Jul 2024
- First submitted
- 27 Apr 2023
- Last updated
- 29 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial of Inhaled Sedation With Sevoflurane in Critically Ill Patients at Risk of Developing the Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT05849779
- Acronym / sponsor ID
- IPA / IPA trial (AOI 2019 JABAUDON)
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- ARDS, Sedation, Inhaled sevoflurane
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 24 Jul 2023 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 Jul 2026 (estimated)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
MAIN OBJECTIVE To assess the efficacy of inhaled sevoflurane, compared to current intravenous sedation practice, for improving PaO2/FiO2 in ICU patients at high risk for ARDS.
HYPOTHESIS The investigators hypothesized that a strategy of inhaled sedation with sevoflurane could be more effective than current intravenous sedation practice at improving pulmonary function during the early days of ICU admission, in patients at risk of ARDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Inhaled sedation with sevoflurane | Experimental | Drug: Inhaled sedation with sevofluraneSevoflurane as vaporized via the Anesthesia Conserving Device (Sedaconda-ACD-S, Sedana Medical, Danderyd, Sweden). |
| Intravenous sedation | Active comparator | Drug: Intravenous sedation (current practice)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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled sedation with sevofluraneAlso: ExperimentalIn 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). | Drug | Inhaled sedation with sevoflurane |
| Intravenous sedation (current practice)Also: ControlIn 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). | Drug | Intravenous sedation |
Primary outcome
PaO2/FiO2 ratio
Time frame: within 5 days from randomization
longitudinal evolution in the PaO2/FiO2 ratio
19 secondary outcomes
Progression to ARDS
Time frame: within 5 days from randomization
Rate of pneumonia
Time frame: 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
Time frame: 28 days after randomization
Organ failure to day 5
Time frame: 5 days after randomization
Mortality at day 28
Time frame: 28 days after randomization
Length of ICU-stay up to 28 days
Time frame: 28 days after randomization
Physiological measures: Oxygenation
Time frame: 28 days after randomization
Physiological measures: PaCO2
Time frame: 28 days after randomization
Physiological measures: pH
Time frame: 28 days after randomization
Physiological measures: PEEP
Time frame: 28 days after randomization
Physiological measures: Plateau pressure
Time frame: 28 days after randomization
Physiological measures: Pneumothorax
Time frame: 28 days after randomization
Physiological measures: Switch from controlled to pressure-support ventilation
Time frame: 28 days after randomization
Physiological measures: Airway occlusion pressure
Time frame: 28 days after randomization
Hemodynamic measures
Time frame: 28 days after randomization
Physiological measures: Acute kidney injury
Time frame: 28 days after randomization
Physiological measures: Supraventricular tachycardia
Time frame: 28 days after randomization
ICU-acquired delirium
Time frame: 28 days after randomization
Biomarker measurements
Time frame: from inclusion to 5 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthieu JABAUDON principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Inhaled sedation with sevoflurane and Intravenous sedation (current practice) in people with Acute Respiratory Distress Syndrome, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lise Laclautre (+33473754963, llaclautre_perrier@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PaO2/FiO2 ratio (time frame: within 5 days from randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2024.