Clinical trial NCT05259631: Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS
Official title: Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS: A Multicentral Randomized Pilot Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Keywords: Acute Respiratory Distress Syndrome
Sedation
Sevoflurane
Propofol
Volatile anesthetics
Intravenous anesthetics
Inhalational anesthetics
Intensive care unit
Lead sponsor: Negovsky Reanimatology Research Institute
Sponsor class: OTHER_GOV
First posted: 2022-02-28
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: P/F ratio
timeFrame: day 2 after the randomization
Secondary outcomes:
measure: 28-days mortality
timeFrame: 28 day
measure: 6-months mortality
timeFrame: 6 months
measure: 1-year mortality
timeFrame: 1 year
measure: Length of stay in the intensive care unit
timeFrame: 1 year
measure: Length of hospitalization
timeFrame: 1 year
measure: Ventilator free days in ICU
timeFrame: 1 year
measure: Ventilator free days during hospitalization
timeFrame: 1 year
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Demikhov Municipal Clinical Hospital 68
Study officials:
affiliation: Negovsky Reanimatology Research Institute
name: Valery Likhvantsev
role: PRINCIPAL_INVESTIGATOR
References: