ARDSPhase 3NCT04530188
Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS
A Phase 3 study testing Sevoflurane and Propofol in people with ARDS and ARDS, Human, run by Bicetre Hospital.
Trial summary
The study will investigate the effects of inhaled sedation with sevoflurane using the AnaConDa device on extravascular lung water index (EVLWi) and the pulmonary vascular permeability index (PVPI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- ARDS, ARDS, Human
- What is being tested?
- Sevoflurane and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- No sites listed yet
- Study dates
- Nov 2020to Nov 2022
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Presence of acute respiratory distress syndrome 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
- PaO2/FiO2 <200 mmHg after meeting inclusion criteria and before randomization
Who cannot join
- Absence of affiliation to the French Sociale security
- Patient under a tutelage measure or placed under judicial protection
- Known pregnancy
- Currently receiving ECMO therapy
- Chronic liver disease defined as a Child-Pugh score of 12-15
- Severe hepatic failure
Show all 15Show fewer
- 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
- Medical history of malignant hyperthermia
- Medical history of liver disease attributed to previous exposure to a halogenated agent
- Known hypersensitivity to propofol or any of its components
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With Acute Respiratory Distress Syndrome
The study will investigate the effects of inhaled sedation with sevoflurane using the AnaConDa device on extravascular lung water index (EVLWi) and the pulmonary vascular permeability index (PVPI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). Improvement in oxygenation and decreases in lung inflammatory response has been demonstrated in patients with ARDS compared with intravenous sedation. However, preclinical data showing a decrease in lung edema has not been confirmed. The hypothesis is that inhaled sedation with sevoflurane reduces EVLWi and PVPI in patients with ARDS, assessed with the PiCCO device. Patients will receive either inhaled sedation (interventional group), or a sedation with propofol (control group). Both will be associated with remifentanil. Sedation will be monitored by bispectral index with a targeted value of 30-50. The primary outcome will be daily assessment of EVLWi and PVPI over time in patients sedated with sevoflurane compared to propofol. Secondary outcomes will include value of PVPI and EVLW at 48h after intubation, fluid administration, need in norepinephrine, time between cessation of sedation and trial of weaning sedation, ventilation free days, mortality at day 28, the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2), plasma and alveolar levels of cytokines (tumor necrosis factor (TNF)-α, interleukine (IL)-1β, IL-6, IL-8). These blood and alveolar samples will be done at baseline, on day 2 and on day 5. A sub-group analysis will be done in Covid-19 related ARDS. Decrease in PVPI and EVLWi with inhaled sevoflurane may be related to the decrease in lung edema in ARDS patients and may ultimately improve patient outcome.
Read the detailed description
Background:
Inhaled sedation with volatile anesthetic agents has been proposed as an efficient and safe alternative to usual intravenous sedation such as propofol or midazolam in the intensive care unit. In acute respiratory distress syndrome (ARDS) models, preclinical studies comparing inhaled sedation to intravenous sedation showed that sedation with sevoflurane improves oxygenation, reduces the lung and systemic inflammatory response, decreases formation of alveolar edema and is associated with a less pronounced increase in extravascular lung water (EVLW, the amount of water contained in the lungs outside the pulmonary vasculature) or pulmonary vascular permeability index (PVPI), the ratio of EVLW over the pulmonary blood volume). Although benefits of inhaled sedation on inflammation and oxygenation have been shown in humans, its direct effect on EVLW or PVPI has never been evaluated in patients with ARDS. It could be important as their levels are factors independently associated with mortality in patients with ARDS.
Aim:
To evaluate the effect of inhaled sedation with sevoflurane in comparison with sedation with propofol on the degree of PVPI and the amount of EVLW in patients with moderate-to-severe ARDS.
Hypothesis:
The hypothesis is that inhaled sedation with sevoflurane reduces PVPI and EVLW in patients with ARDS compared to sedation with propofol.
- Conditions
- ARDS, ARDS, Human
- Being tested
- Sevoflurane, Propofol
- Keywords
- ARDS, inhaled anesthetic, sevoflurane, extravascular lung water, pulmonary vascular permeability
- 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.
SevofluraneDrug
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
PropofolDrug
Intravenous sedation with propofol, as already used in our ICU
| Study group | Role | What they receive |
|---|---|---|
| inhaled sedation with sevoflurane | Experimental | Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden) Receives: Drug: Sevoflurane |
| intravenous sedation with propofol | Active comparator | intravenous sedation with propofol, as already used in our ICU Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time course of extravascular lung water (EVLW)
EVLW is the amount of water contained in the lungs outside the pulmonary vasculature. It can be measured using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Measured: Through study completion, up to 90 days
Time course of pulmonary vascular permeability index (PVPI)
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Measured: Through study completion, up to 90 days
Secondary outcomes (19)
Value of extravascular lung water index (EVLW)
EVLW is the amount of water contained in the lungs outside the pulmonary vasculature. It can be measured using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Measured: Day 2
Value of extravascular lung water index (EVLW)
EVLW is the amount of water contained in the lungs outside the pulmonary vasculature. It can be measured using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Measured: Day 5
Value of pulmonary vascular permeability index (PVPI)
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Measured: Day 2
Value of pulmonary vascular permeability index (PVPI)
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Measured: Day 5
Daily fluid balance
Fluid balance will be calculated daily as fluid intake minus fluid output. It is expressed in mL/day.
Measured: Through study completion, up to 90 days
Need in catecholamines
Measured: Through study completion, up to 90 days
time between sedation cessation and first weaning trial
Measured: Through study completion, up to 90 days
Ventilator free days
ventilator-free days to taking into account death as a competing event
Measured: Day 28
Mortality
Measured: Day 28
Oxygenation assessed with PaO2/FiO2 ratio
Measured: Day 2
Oxygenation assessed with PaO2/FiO2 ratio
Measured: Day 5
Oxygenation assessed with PaO2/FiO2 ratio
Measured: Through study completion, up to 90 days
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Blood samples and alveolar samples from a bronchoalveolar lavage to constitute a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane in patients with ARDS
Measured: At enrollment
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Blood samples and alveolar samples from a bronchoalveolar lavage to constitute a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane on inflammation in patients with ARDS
Measured: Day 2
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Blood samples and alveolar samples from a bronchoalveolar lavage to constitute a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane on inflammation in patients with ARDS
Measured: Day 5
Cardiac index
Data provided by transpulmonary thermodilution. (unit: L/min/m2)
Measured: Through study completion, up to 90 days
Global End Diastolic Volume index
Data provided by transpulmonary thermodilution. (unit: mL/m2)
Measured: Through study completion, up to 90 days
Blood pressure
Systolic, diastolic and mean blood pressure
Measured: Through study completion, up to 90 days
Correlation between data provided by transpulmonary thermodilution (extravascular lung water, pulmonary vascular permeability index, cardiac index, global end-diastolic volume) and 28-day mortality
maximal or minimal values, trend in values,
Measured: up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2020
- Study startNov 2020 (estimated)
- Primary completionMay 2022 (estimated)
- Study completionNov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARDSStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bicetre Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Lai, Bicetre Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04530188
- Sponsor's protocol ID
- BicetreH
- Status last verified
- Aug 2020
- First submitted
- 14 Aug 2020
- Last updated
- 28 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04530188
- Acronym / sponsor ID
- BicetreH
- Conditions
- ARDS, ARDS, Human
- Keywords
- ARDS, inhaled anesthetic, sevoflurane, extravascular lung water, pulmonary vascular permeability
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Bicetre HospitalUniversity, hospital or other
- Study start
- Nov 2020 (estimated)
- Primary completion
- May 2022 (estimated)
- Study completion
- Nov 2022 (estimated)
- First posted
- 28 Aug 2020 (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.
The study will investigate the effects of inhaled sedation with sevoflurane using the AnaConDa device on extravascular lung water index (EVLWi) and the pulmonary vascular permeability index (PVPI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). Improvement in oxygenation and decreases in lung inflammatory response has been demonstrated in patients with ARDS compared with intravenous sedation. However, preclinical data showing a decrease in lung edema has not been confirmed. The hypothesis is that inhaled sedation with sevoflurane reduces EVLWi and PVPI in patients with ARDS, assessed with the PiCCO device. Patients will receive either inhaled sedation (interventional group), or a sedation with propofol (control group). Both will be associated with remifentanil. Sedation will be monitored by bispectral index with a targeted value of 30-50. The primary outcome will be daily assessment of EVLWi and PVPI over time in patients sedated with sevoflurane compared to propofol. Secondary outcomes will include value of PVPI and EVLW at 48h after intubation, fluid administration, need in norepinephrine, time between cessation of sedation and trial of weaning sedation, ventilation free days, mortality at day 28, the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2), plasma and alveolar levels of cytokines (tumor necrosis factor (TNF)-α, interleukine (IL)-1β, IL-6, IL-8). These blood and alveolar samples will be done at baseline, on day 2 and on day 5. A sub-group analysis will be done in Covid-19 related ARDS. Decrease in PVPI and EVLWi with inhaled sevoflurane may be related to the decrease in lung edema in ARDS patients and may ultimately improve patient outcome.
Detailed description
Background:
Inhaled sedation with volatile anesthetic agents has been proposed as an efficient and safe alternative to usual intravenous sedation such as propofol or midazolam in the intensive care unit. In acute respiratory distress syndrome (ARDS) models, preclinical studies comparing inhaled sedation to intravenous sedation showed that sedation with sevoflurane improves oxygenation, reduces the lung and systemic inflammatory response, decreases formation of alveolar edema and is associated with a less pronounced increase in extravascular lung water (EVLW, the amount of water contained in the lungs outside the pulmonary vasculature) or pulmonary vascular permeability index (PVPI), the ratio of EVLW over the pulmonary blood volume). Although benefits of inhaled sedation on inflammation and oxygenation have been shown in humans, its direct effect on EVLW or PVPI has never been evaluated in patients with ARDS. It could be important as their levels are factors independently associated with mortality in patients with ARDS.
Aim:
To evaluate the effect of inhaled sedation with sevoflurane in comparison with sedation with propofol on the degree of PVPI and the amount of EVLW in patients with moderate-to-severe ARDS.
Hypothesis:
The hypothesis is that inhaled sedation with sevoflurane reduces PVPI and EVLW in patients with ARDS compared to sedation with propofol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| inhaled sedation with sevoflurane | Experimental | Drug: SevofluraneInhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden) |
| intravenous sedation with propofol | Active comparator | Drug: Propofolintravenous sedation with propofol, as already used in our ICU |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years
- Presence of acute respiratory distress syndrome 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
Key exclusion criteria (15 listed)
- Absence of affiliation to the French Sociale security
- Patient under a tutelage measure or placed under judicial protection
- Known pregnancy
- Currently receiving ECMO therapy
- Chronic liver disease defined as a Child-Pugh score of 12-15
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 |
|---|---|---|
| SevofluraneInhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden) | Drug | inhaled sedation with sevoflurane |
| PropofolIntravenous sedation with propofol, as already used in our ICU | Drug | intravenous sedation with propofol |
Primary outcome
Time course of extravascular lung water (EVLW)
Time frame: Through study completion, up to 90 days
EVLW is the amount of water contained in the lungs outside the pulmonary vasculature. It can be measured using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Time course of pulmonary vascular permeability index (PVPI)
Time frame: Through study completion, up to 90 days
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
19 secondary outcomes
Value of extravascular lung water index (EVLW)
Time frame: Day 2
Value of extravascular lung water index (EVLW)
Time frame: Day 5
Value of pulmonary vascular permeability index (PVPI)
Time frame: Day 2
Value of pulmonary vascular permeability index (PVPI)
Time frame: Day 5
Daily fluid balance
Time frame: Through study completion, up to 90 days
Need in catecholamines
Time frame: Through study completion, up to 90 days
time between sedation cessation and first weaning trial
Time frame: Through study completion, up to 90 days
Ventilator free days
Time frame: Day 28
Mortality
Time frame: Day 28
Oxygenation assessed with PaO2/FiO2 ratio
Time frame: Day 2
Oxygenation assessed with PaO2/FiO2 ratio
Time frame: Day 5
Oxygenation assessed with PaO2/FiO2 ratio
Time frame: Through study completion, up to 90 days
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Time frame: At enrollment
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Time frame: Day 2
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Time frame: Day 5
Cardiac index
Time frame: Through study completion, up to 90 days
Global End Diastolic Volume index
Time frame: Through study completion, up to 90 days
Blood pressure
Time frame: Through study completion, up to 90 days
Correlation between data provided by transpulmonary thermodilution (extravascular lung water, pulmonary vascular permeability index, cardiac index, global end-diastolic volume) and 28-day mortality
Time frame: up to 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2020.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sevoflurane and Propofol in people with ARDS and ARDS, Human, run by Bicetre Hospital.
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 7 inclusion and 15 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 28 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
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 Xavier Monnet, MD, PhD (+33-(0)6660862669, xavier.monnet@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time course of extravascular lung water (EVLW) (time frame: Through study completion, up to 90 days). The study lists 2 primary outcomes in all. 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 28 Aug 2020.