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

NCT05259631 | Suspended Phase 3 DMC

• 1 other identifier: INVERSE
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

Acute Respiratory Distress Syndrome; Sedation; Sevoflurane; Propofol; Volatile anesthetics; Intravenous anesthetics; Inhalational anesthetics; Intensive care unit

Outcome Measures

Primary Outcomes (1)

• P/F ratio

  PaO2 divided on FiO2

  day 2 after the randomization

Secondary Outcomes (7)

• 28-days mortality

  28 day

• 6-months mortality

  6 months

• 1-year mortality

  1 year

• Length of stay in the intensive care unit

  1 year

• Length of hospitalization

  1 year

Study Arms (2)

Inhalational sedation

EXPERIMENTAL

Drug: Sevoflurane

Intravenous sedation

ACTIVE COMPARATOR

Drug: Propofol

Interventions

Sevoflurane DRUG

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

Inhalational sedation

Propofol DRUG

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

Intravenous sedation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Negovsky Reanimatology Research Institute: lead

Study Sites (1)

Demikhov Municipal Clinical Hospital 68

Moscow, Russia

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Sevoflurane; Propofol

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Valery Likhvantsev

  Negovsky Reanimatology Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Research V. Negovsky Reanimatology Research Institute

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: February 28, 2022
• Study Start: March 14, 2022
• Primary Completion: February 25, 2025
• Study Completion: February 25, 2026
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)