Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS

NCT04530188 | Unknown Phase 3

• 1 other identifier: BicetreH
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief 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). 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.

Conditions

ARDS; ARDS, Human

Keywords

ARDS; inhaled anesthetic; sevoflurane; extravascular lung water; pulmonary vascular permeability

Outcome Measures

Primary Outcomes (2)

• 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)

  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)

  Through study completion, up to 90 days

Secondary Outcomes (19)

• Value of extravascular lung water index (EVLW)

  Day 2

• Value of extravascular lung water index (EVLW)

  Day 5

• Value of pulmonary vascular permeability index (PVPI)

  Day 2

• Value of pulmonary vascular permeability index (PVPI)

  Day 5

• Daily fluid balance

  Through study completion, up to 90 days

Study Arms (2)

inhaled sedation with sevoflurane

EXPERIMENTAL

Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)

Drug: Sevoflurane

intravenous sedation with propofol

ACTIVE COMPARATOR

intravenous sedation with propofol, as already used in our ICU

Drug: Propofol

Interventions

Sevoflurane DRUG

Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)

inhaled sedation with sevoflurane

Propofol DRUG

Intravenous sedation with propofol, as already used in our ICU

intravenous sedation with propofol

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bicetre Hospital: lead

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

Central Study Contacts

Xavier Monnet, MD, PhD

CONTACT

+33-(0)6660862669; xavier.monnet@aphp.fr

Christopher lai, MD

CONTACT

+33-(0)145212671; christopher.lai@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 28, 2020
• Study Start: November 1, 2020
• Primary Completion: May 1, 2022
• Study Completion: November 1, 2022
• Last Updated: August 28, 2020

Record last verified: 2020-08