- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04530188
Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS
Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With Acute Respiratory Distress Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background:
Inhaled sedation with volatile anesthetic agents has been proposed as an efficient and safe alternative to usual intravenous sedation such as propofol or midazolam in the intensive care unit. In acute respiratory distress syndrome (ARDS) models, preclinical studies comparing inhaled sedation to intravenous sedation showed that sedation with sevoflurane improves oxygenation, reduces the lung and systemic inflammatory response, decreases formation of alveolar edema and is associated with a less pronounced increase in extravascular lung water (EVLW, the amount of water contained in the lungs outside the pulmonary vasculature) or pulmonary vascular permeability index (PVPI), the ratio of EVLW over the pulmonary blood volume). Although benefits of inhaled sedation on inflammation and oxygenation have been shown in humans, its direct effect on EVLW or PVPI has never been evaluated in patients with ARDS. It could be important as their levels are factors independently associated with mortality in patients with ARDS.
Aim:
To evaluate the effect of inhaled sedation with sevoflurane in comparison with sedation with propofol on the degree of PVPI and the amount of EVLW in patients with moderate-to-severe ARDS.
Hypothesis:
The hypothesis is that inhaled sedation with sevoflurane reduces PVPI and EVLW in patients with ARDS compared to sedation with propofol.
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Xavier Monnet, MD, PhD
- Phone Number: +33-(0)6660862669
- Email: xavier.monnet@aphp.fr
Study Contact Backup
- Name: Christopher Lai, MD
- Phone Number: +33-(0)145212671
- Email: christopher.lai@aphp.fr
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- PaO2/FiO2 <200 mmHg after meeting inclusion criteria and before randomization
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: inhaled sedation with sevoflurane
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
|
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
|
Active Comparator: intravenous sedation with propofol
intravenous sedation with propofol, as already used in our ICU
|
Intravenous sedation with propofol, as already used in our ICU
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time course of extravascular lung water (EVLW)
Time Frame: Through study completion, up to 90 days
|
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)
Time Frame: Through study completion, up to 90 days
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality
Time Frame: Day 28
|
Day 28
|
|
Value of extravascular lung water index (EVLW)
Time Frame: Day 2
|
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)
|
Day 2
|
Value of extravascular lung water index (EVLW)
Time Frame: Day 5
|
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)
|
Day 5
|
Value of pulmonary vascular permeability index (PVPI)
Time Frame: Day 2
|
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
|
Day 2
|
Value of pulmonary vascular permeability index (PVPI)
Time Frame: Day 5
|
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
|
Day 5
|
Daily fluid balance
Time Frame: Through study completion, up to 90 days
|
Fluid balance will be calculated daily as fluid intake minus fluid output.
It is expressed in mL/day.
|
Through study completion, up to 90 days
|
Need in catecholamines
Time Frame: Through study completion, up to 90 days
|
Through study completion, up to 90 days
|
|
time between sedation cessation and first weaning trial
Time Frame: Through study completion, up to 90 days
|
Through study completion, up to 90 days
|
|
Ventilator free days
Time Frame: Day 28
|
ventilator-free days to taking into account death as a competing event
|
Day 28
|
Oxygenation assessed with PaO2/FiO2 ratio
Time Frame: Day 2
|
Day 2
|
|
Oxygenation assessed with PaO2/FiO2 ratio
Time Frame: Day 5
|
Day 5
|
|
Oxygenation assessed with PaO2/FiO2 ratio
Time Frame: Through study completion, up to 90 days
|
Through study completion, up to 90 days
|
|
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Time Frame: At enrollment
|
Blood samples and alveolar samples from a bronchoalveolar lavage to constitute a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane in patients with ARDS
|
At enrollment
|
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Time Frame: Day 2
|
Blood samples and alveolar samples from a bronchoalveolar lavage to constitute a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane on inflammation in patients with ARDS
|
Day 2
|
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Time Frame: Day 5
|
Blood samples and alveolar samples from a bronchoalveolar lavage to constitute a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane on inflammation in patients with ARDS
|
Day 5
|
Cardiac index
Time Frame: Through study completion, up to 90 days
|
Data provided by transpulmonary thermodilution.
(unit: L/min/m2)
|
Through study completion, up to 90 days
|
Global End Diastolic Volume index
Time Frame: Through study completion, up to 90 days
|
Data provided by transpulmonary thermodilution.
(unit: mL/m2)
|
Through study completion, up to 90 days
|
Blood pressure
Time Frame: Through study completion, up to 90 days
|
Systolic, diastolic and mean blood pressure
|
Through study completion, up to 90 days
|
Correlation between data provided by transpulmonary thermodilution (extravascular lung water, pulmonary vascular permeability index, cardiac index, global end-diastolic volume) and 28-day mortality
Time Frame: up to 28 days
|
maximal or minimal values, trend in values,
|
up to 28 days
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Respiration Disorders
- Lung Diseases
- Respiratory Distress Syndrome
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Platelet Aggregation Inhibitors
- Hypnotics and Sedatives
- Anesthetics, Inhalation
- Propofol
- Sevoflurane
Other Study ID Numbers
- BicetreH
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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