NCT05259631

Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS

Suspended Phase 3 Last updated 1 February 2023

What this trial tests

Phase 3 trial testing Sevoflurane in Acute Respiratory Distress Syndrome in 310 participants. Suspended.

Timeline

14 March 2022

Primary endpoint
25 February 2025

25 February 2026

Quick facts

Lead sponsor	Negovsky Reanimatology Research Institute
Phase	Phase 3
Status	Suspended
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	310
Start date	14 March 2022
Primary completion	25 February 2025
Estimated completion	25 February 2026
Sites	1 location across Russia

Drugs / interventions tested

• Sevoflurane — full drug profile →
• Propofol (Propofol) — full drug profile →

Conditions studied

• Acute Respiratory Distress Syndrome — all drugs for Acute Respiratory Distress Syndrome →

Sponsor

Negovsky Reanimatology Research Institute

Who can join

18 and older, any sex, with Acute Respiratory Distress Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.