Acute Respiratory Distress SyndromePhase 3NCT05259631
Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS
A Phase 3 study testing Sevoflurane and Propofol in people with Acute Respiratory Distress Syndrome, run by Negovsky Reanimatology Research Institute at 1 site in Russia.
Trial summary
The American European Consensus Conference (AECC) 1994 defined acute respiratory distress syndrome (ARDS) as an acute inflammatory syndrome manifesting as diffuse pulmonary edema and respiratory failure that cannot be explained by, but may co-exist with, left-sided heart failure. 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?
- Sevoflurane and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 310 participants
- Where
- 1 siteRussia
- Study dates
- 14 Mar 2022to 25 Feb 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
- Endotracheal intubation or tracheostomy
- Timing: Acute onset of new or worsening of chronic respiratory symptoms within 72 hours before the randomization
- Chest imaging: Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules
- Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload
- Oxygenation: 100 mm Hg < PaO2/FiO2 ≤ 200 mm Hg with PEEP ≥ 5 cm H2O
Who cannot join
- History or family history of malignant hyperthermia
- History of propofol infusion syndrome
- Documented or suspected increased intracranial pressure
- Chronic restrictive pulmonary disease
- Chronic obstructive pulmonary disease
- Neuromuscular disease
Show all 14Show fewer
- Chest wall disorder
- Pulmonary vascular disease
- NYHA class ≥ 3
- Severe pulmonary hypertension (mean pulmonary artery pressure > 40 mmHg)
- Documented ongoing COVID-19 infection
- Ongoing immunosuppressive therapy
- Previous randomization in this trial
- Post randomization exclusion criterion: Documented ongoing COVID-19 infection during the first 48 hours after the randomization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS: A Multicentral Randomized Pilot Trial
The American European Consensus Conference (AECC) 1994 defined acute respiratory distress syndrome (ARDS) as an acute inflammatory syndrome manifesting as diffuse pulmonary edema and respiratory failure that cannot be explained by, but may co-exist with, left-sided heart failure. During the sequel Conference of the European Society of Intensive Care Medicine, in 2012 minor changes were made, and since that so-called Berlin definition of ARDS is used worldwide for the description of this severe disease. Three grades of severity were proposed to distinguish ARDS according to the level of hypoxemia with a mortality of 24% in patients with mild ARDS, rising to 48% in those with severe ones.
Systemic inflammation is considered to be the main reason of ARDS. Activated neutrophils interact with the alveolar-capillary membrane causing the increasing permeability with the sequence lung edema's development. Inflammatory exudate inactivates surfactant leading to collapse and consolidation of distal airspaces with progressive loss of the lung's gas exchange surface area. Unfortunately, systemic inflammatory response syndrome (SIRS) simultaneously inhibits the mechanism of active pulmonary vasoconstriction and allows deoxygenated blood to pass through unventilated areas of the lung boosting the right-to-left shunt. Both mechanisms lead to hypoxemia, which is the main and obligatory feature of ARDS.
Read more
Actually, endothelial dysfunction and transcapillary leakage seem to be one of the main steps in the development of respiratory failure during ARDS. Last decades it was found out that glycocalyx is also participating in this process too.
Thus, it became clear that substances preserving endothelium and glycocalyx from SIRS-causing damage may have a beneficial effect in ARDS treatment. It seems to be crucially important so as the majority of drugs failed to demonstrate any positive effects in terms of ARDS treatment.
To the moment we have some evidence, which came from experimental studies, that halogenated anesthetics can preserve glycocalyx against ischemia-reperfusion injury.
The primary objective for the multicentral INVERSE Trial will be to determine the effects of inhalational (sevoflurane) versus intravenous (propofol) sedation on P/F ratio on the second day, hospital mortality and ICU (intensive care unit), and in-hospital length of stay in adults with a moderate form of ARDS.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Sevoflurane, Propofol
- Keywords
- Acute Respiratory Distress Syndrome, Sedation, Sevoflurane, Propofol, Volatile anesthetics, Intravenous anesthetics, Inhalational anesthetics, Intensive care unit
- 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
Patients are to be sedated by sevoflurane inhalation. For this purpose, any certificated devices are suitable - AnaConDa or Mirus evenly. Starting dose of sevoflurane is to be 2 ml/h and may be modified at the discretion of the attending intensivist to achieve and maintain the target level of sedation
PropofolDrug
Patients of this group will receive an intravenous infusion of propofol with starting dose of 1 mg/kg/h. The precise dose to maintain the desired level of sedation is left at the discretion of the attending intensivist and may be revised at any time. The upper dose limit for propofol is 4 mg/kg/h. In case of tolerance to propofol infusion, midazolam or antipsychotics (haloperidol) can be added to achieve the desired level of sedation
| Study group | Role | What they receive |
|---|---|---|
| Inhalational sedation | Experimental | Not described Receives: Drug: Sevoflurane |
| Intravenous sedation | Active comparator | Not described Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
P/F ratio
PaO2 divided on FiO2
Measured: day 2 after the randomization
Secondary outcomes (7)
28-days mortality
number of deaths
Measured: 28 day
6-months mortality
number of deaths
Measured: 6 months
1-year mortality
number of death
Measured: 1 year
Length of stay in the intensive care unit
number of days in the intensive care unit
Measured: 1 year
Length of hospitalization
number of days in hospital
Measured: 1 year
Ventilator free days in ICU
number of days in ICU - number of days on mechanical ventilation
Measured: 1 year
Ventilator free days during hospitalization
Length of hospitalization - number of days on mechanical ventilation
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2022
- Study start14 Mar 2022
- Primary completion25 Feb 2025 (estimated)
- Study completion25 Feb 2026 (estimated)
Why it stopped: Financial problems
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.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 310 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Negovsky Reanimatology Research Institute
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Valery Likhvantsev, MD, Negovsky Reanimatology Research Institute
- Investigators
- Valery Likhvantsev, Principal investigator, Negovsky Reanimatology Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05259631
- Sponsor's protocol ID
- INVERSE
- Status last verified
- Jan 2023
- First submitted
- 17 Feb 2022
- Last updated
- 1 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS: A Multicentral Randomized Pilot Trial
- ClinicalTrials.gov ID
- NCT05259631
- Acronym / sponsor ID
- INVERSE
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Acute Respiratory Distress Syndrome, Sedation, Sevoflurane, Propofol, Volatile anesthetics, Intravenous anesthetics, Inhalational anesthetics, Intensive care unit
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Financial problems
- Enrolment
- 310 participants (estimated)
- Lead sponsor
- Negovsky Reanimatology Research InstituteOther government
- Study start
- 14 Mar 2022 (actual)
- Primary completion
- 25 Feb 2025 (estimated)
- Study completion
- 25 Feb 2026 (estimated)
- First posted
- 28 Feb 2022 (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 American European Consensus Conference (AECC) 1994 defined acute respiratory distress syndrome (ARDS) as an acute inflammatory syndrome manifesting as diffuse pulmonary edema and respiratory failure that cannot be explained by, but may co-exist with, left-sided heart failure. During the sequel Conference of the European Society of Intensive Care Medicine, in 2012 minor changes were made, and since that so-called Berlin definition of ARDS is used worldwide for the description of this severe disease. Three grades of severity were proposed to distinguish ARDS according to the level of hypoxemia with a mortality of 24% in patients with mild ARDS, rising to 48% in those with severe ones.
Systemic inflammation is considered to be the main reason of ARDS. Activated neutrophils interact with the alveolar-capillary membrane causing the increasing permeability with the sequence lung edema's development. Inflammatory exudate inactivates surfactant leading to collapse and consolidation of distal airspaces with progressive loss of the lung's gas exchange surface area. Unfortunately, systemic inflammatory response syndrome (SIRS) simultaneously inhibits the mechanism of active pulmonary vasoconstriction and allows deoxygenated blood to pass through unventilated areas of the lung boosting the right-to-left shunt. Both mechanisms lead to hypoxemia, which is the main and obligatory feature of ARDS.
Actually, endothelial dysfunction and transcapillary leakage seem to be one of the main steps in the development of respiratory failure during ARDS. Last decades it was found out that glycocalyx is also participating in this process too.
Thus, it became clear that substances preserving endothelium and glycocalyx from SIRS-causing damage may have a beneficial effect in ARDS treatment. It seems to be crucially important so as the majority of drugs failed to demonstrate any positive effects in terms of ARDS treatment.
To the moment we have some evidence, which came from experimental studies, that halogenated anesthetics can preserve glycocalyx against ischemia-reperfusion injury.
The primary objective for the multicentral INVERSE Trial will be to determine the effects of inhalational (sevoflurane) versus intravenous (propofol) sedation on P/F ratio on the second day, hospital mortality and ICU (intensive care unit), and in-hospital length of stay in adults with a moderate form of ARDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhalational sedation | Experimental | Drug: Sevoflurane |
| Intravenous sedation | Active comparator | Drug: Propofol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age > 18
- Endotracheal intubation or tracheostomy
- Timing: Acute onset of new or worsening of chronic respiratory symptoms within 72 hours before the randomization
- Chest imaging: Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules
- Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload
Key exclusion criteria (14 listed)
- History or family history of malignant hyperthermia
- History of propofol infusion syndrome
- Documented or suspected increased intracranial pressure
- Chronic restrictive pulmonary disease
- Chronic obstructive pulmonary disease
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 |
|---|---|---|
| SevofluranePatients are to be sedated by sevoflurane inhalation. For this purpose, any certificated devices are suitable - AnaConDa or Mirus evenly. Starting dose of sevoflurane is to be 2 ml/h and may be modified at the discretion of the attending intensivist to achieve and maintain the target level of sedation | Drug | Inhalational sedation |
| PropofolPatients of this group will receive an intravenous infusion of propofol with starting dose of 1 mg/kg/h. The precise dose to maintain the desired level of sedation is left at the discretion of the attending intensivist and may be revised at any time. The upper dose limit for propofol is 4 mg/kg/h. In case of tolerance to propofol infusion, midazolam or antipsychotics (haloperidol) can be added to achieve the desired level of sedation | Drug | Intravenous sedation |
Primary outcome
P/F ratio
Time frame: day 2 after the randomization
PaO2 divided on FiO2
7 secondary outcomes
28-days mortality
Time frame: 28 day
6-months mortality
Time frame: 6 months
1-year mortality
Time frame: 1 year
Length of stay in the intensive care unit
Time frame: 1 year
Length of hospitalization
Time frame: 1 year
Ventilator free days in ICU
Time frame: 1 year
Ventilator free days during hospitalization
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2023.
- Individual participant dataSharing planned: No
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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.
Valery Likhvantsev principal investigator
Negovsky Reanimatology Research Institute
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 Sevoflurane and Propofol in people with Acute Respiratory Distress Syndrome, run by Negovsky Reanimatology Research Institute at 1 site in Russia.
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 6 inclusion and 14 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: paused, as of the sponsor's last update on 1 Feb 2023. 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 Russia. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
P/F ratio (time frame: day 2 after the 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 1 Feb 2023.