Back to resultsEffects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS
Primary Purpose
ARDS, ARDS, Human
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sevoflurane
Propofol
Sponsored by
About this trial
This is an interventional treatment trial for ARDS focused on measuring ARDS, inhaled anesthetic, sevoflurane, extravascular lung water, pulmonary vascular permeability
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
inhaled sedation with sevoflurane
intravenous sedation with propofol
Arm Description
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
intravenous sedation with propofol, as already used in our ICU
Outcomes
Primary Outcome Measures
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)
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)
Secondary Outcome Measures
Value of extravascular lung water index (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)
Value of extravascular lung water index (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)
Value of pulmonary vascular permeability index (PVPI)
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Value of pulmonary vascular permeability index (PVPI)
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Daily fluid balance
Fluid balance will be calculated daily as fluid intake minus fluid output. It is expressed in mL/day.
Need in catecholamines
time between sedation cessation and first weaning trial
Ventilator free days
ventilator-free days to taking into account death as a competing event
Mortality
Oxygenation assessed with PaO2/FiO2 ratio
Oxygenation assessed with PaO2/FiO2 ratio
Oxygenation assessed with PaO2/FiO2 ratio
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
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
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
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
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
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
Cardiac index
Data provided by transpulmonary thermodilution. (unit: L/min/m2)
Global End Diastolic Volume index
Data provided by transpulmonary thermodilution. (unit: mL/m2)
Blood pressure
Systolic, diastolic and mean blood pressure
Correlation between data provided by transpulmonary thermodilution (extravascular lung water, pulmonary vascular permeability index, cardiac index, global end-diastolic volume) and 28-day mortality
maximal or minimal values, trend in values,
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04530188
Brief Title
Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS
Official Title
Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With Acute Respiratory Distress Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 2020 (Anticipated)
Primary Completion Date
May 2022 (Anticipated)
Study Completion Date
November 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bicetre Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ARDS, ARDS, Human
Keywords
ARDS, inhaled anesthetic, sevoflurane, extravascular lung water, pulmonary vascular permeability
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
inhaled sedation with sevoflurane
Arm Type
Experimental
Arm Description
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
Arm Title
intravenous sedation with propofol
Arm Type
Active Comparator
Arm Description
intravenous sedation with propofol, as already used in our ICU
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Intervention Description
Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Intravenous sedation with propofol, as already used in our ICU
Primary Outcome Measure Information:
Title
Time course of extravascular lung water (EVLW)
Description
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)
Time Frame
Through study completion, up to 90 days
Title
Time course of pulmonary vascular permeability index (PVPI)
Description
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Time Frame
Through study completion, up to 90 days
Secondary Outcome Measure Information:
Title
Value of extravascular lung water index (EVLW)
Description
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)
Time Frame
Day 2
Title
Value of extravascular lung water index (EVLW)
Description
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)
Time Frame
Day 5
Title
Value of pulmonary vascular permeability index (PVPI)
Description
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Time Frame
Day 2
Title
Value of pulmonary vascular permeability index (PVPI)
Description
PVPI is estimated using the transpulmonary thermodilution technique with the PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany)
Time Frame
Day 5
Title
Daily fluid balance
Description
Fluid balance will be calculated daily as fluid intake minus fluid output. It is expressed in mL/day.
Time Frame
Through study completion, up to 90 days
Title
Need in catecholamines
Time Frame
Through study completion, up to 90 days
Title
time between sedation cessation and first weaning trial
Time Frame
Through study completion, up to 90 days
Title
Ventilator free days
Description
ventilator-free days to taking into account death as a competing event
Time Frame
Day 28
Title
Mortality
Time Frame
Day 28
Title
Oxygenation assessed with PaO2/FiO2 ratio
Time Frame
Day 2
Title
Oxygenation assessed with PaO2/FiO2 ratio
Time Frame
Day 5
Title
Oxygenation assessed with PaO2/FiO2 ratio
Time Frame
Through study completion, up to 90 days
Title
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Description
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
Time Frame
At enrollment
Title
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Description
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
Time Frame
Day 2
Title
Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
Description
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
Time Frame
Day 5
Title
Cardiac index
Description
Data provided by transpulmonary thermodilution. (unit: L/min/m2)
Time Frame
Through study completion, up to 90 days
Title
Global End Diastolic Volume index
Description
Data provided by transpulmonary thermodilution. (unit: mL/m2)
Time Frame
Through study completion, up to 90 days
Title
Blood pressure
Description
Systolic, diastolic and mean blood pressure
Time Frame
Through study completion, up to 90 days
Title
Correlation between data provided by transpulmonary thermodilution (extravascular lung water, pulmonary vascular permeability index, cardiac index, global end-diastolic volume) and 28-day mortality
Description
maximal or minimal values, trend in values,
Time Frame
up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xavier Monnet, MD, PhD
Phone
+33-(0)6660862669
Email
xavier.monnet@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Christopher lai, MD
Phone
+33-(0)145212671
Email
christopher.lai@aphp.fr
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS
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