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Sevoflurane PharmacokInetics in ARDS (SPIDERMAN)

Primary Purpose

Acute Respiratory Distress Syndrome

Status

Unknown status

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring Nonfocal Acute respiratory distress syndrome, Focal Acute respiratory distress syndrome, Sevoflurane, Pharmacokinetics, Mechanical ventilation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥18 years
Presence for ≤ 12 hours of all of the following conditions, within one week of a clinical insult or new or worsening respiratory symptoms :

a PaO2/FiO2 < 200 mmHg with positive end-expiratory pressure (PEEP) ≥ 8 cmH2O (or, if arterial blood gas not available : SpO2/FiO2 ratio that is equivalent to a PaO2/FiO2 < 200 mmHg with PEEP ≥8 cmH2O, and a confirmatory SpO2/FiO2 ratio between 1-6 hours after the initial SpO2/FiO2 ratio determination) b Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules c 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

Exclusion Criteria:

Lack of informed consent
Continuous sedation with inhaled sevoflurane at enrollment
Currently receiving ECMO therapy
Chronic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting
Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
Body mass index > 40 kg/m2
Chronic liver disease defined as a Child-Pugh score of 12-15
Expected duration of mechanical ventilation < 48 hours
Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL
Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation
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
Suspected or proven intracranial hypertension
Know pregnancy - Pregnancy testing will be systematically performed to rule out pregnancy in female patients of reproductive age
Enrollment in another interventional ARDS trial with direct impact on sedation and PEEP
Endotracheal ventilation for greater than 120 hours (5 days)
PaO2/FiO2 (if available) > 200 mmHg after meeting inclusion criteria and before start of the study

Sites / Locations

Centre Jean PerrinRecruiting
CHURecruiting
APHP - University hospital of Saint-Louis

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Nonfocal ARDS

Focal ARDS

Arm Description

ARDS patient with nonfocal lung imaging phenotype

ARDS patient with focal lung imaging phenotype

Outcomes

Primary Outcome Measures

Plasma concentrations of sevoflurane

Secondary Outcome Measures

Plasma concentration of hexafluoroisopropanolol

Fraction of inspired sevoflurane

Fraction of expired sevoflurane

Dose of sevoflurane

Dose of sevoflurane (mg/l)

Infusion duration of sevoflurane

Infusion duration of sevoflurane (min)

Infusion rate of remifentanil

Values of a bispectral index

Full Information

NCT ID

NCT04023305

First Posted

July 10, 2019

Last Updated

May 17, 2021

Sponsor

University Hospital, Clermont-Ferrand

1. Study Identification

Unique Protocol Identification Number

NCT04023305

Brief Title

Sevoflurane PharmacokInetics in ARDS

Acronym

SPIDERMAN

Official Title

Sevoflurane pharmacokInetics During Inhaled Sedation Relies on the Morphotype of ARDS in ICU Patients

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Unknown status

Study Start Date

February 23, 2020 (Actual)

Primary Completion Date

March 1, 2023 (Anticipated)

Study Completion Date

June 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Clermont-Ferrand

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The main objective of this study is to compare the pharmacokinetic models of sevoflurane-induced sedation during ARDS depending on the lung imaging phenotype (focal vs nonfocal phenotypes) The authors hypothesized that sevoflurane used for inhaled sedation could have distinct pharmacokinetic profiles depending on lung imaging phenotypes (focal vs nonfocal) during ARDS in ICU patients.

Detailed Description

Adult patients admitted to the ICU within 12 hours of moderate-severe ARDS onset and under sedation with sevoflurane will be enrolled in the study with inclusion criteria. They will be enrolled, depending on their morphotype (focal or nonfocal), as routinely assessed in participating centers using CT-scan, chest x-ray and/or lung ultrasound. These patients will receive inhaled sevoflurane as a standard practice of sedation that is routinely used in participating ICUs. After inclusion, the mechanical ventilation protocol must be initiated within two hours (if not already being used). In both groups, deep sedation followed by neuromuscular blockade must be initiated within four hours of inclusion. Adult patients admitted to the ICU within 12 hours of moderate-severe ARDS onset and under sedation with sevoflurane will be enrolled in the study with inclusion criteria. They will be enrolled, depending on their morphotype (focal or nonfocal), as routinely assessed in participating centers using CT-scan, chest x-ray and/or lung ultrasound. These patients will receive inhaled sevoflurane as a standard practice of sedation that is routinely used in participating ICUs. After inclusion, the mechanical ventilation protocol must be initiated within two hours (if not already being used). In both groups, deep sedation followed by neuromuscular blockade must be initiated within four hours of inclusion. Blood sample will be collected at different times after the onset of sevoflurane administration and after its cessation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Respiratory Distress Syndrome

Keywords

Nonfocal Acute respiratory distress syndrome, Focal Acute respiratory distress syndrome, Sevoflurane, Pharmacokinetics, Mechanical ventilation

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Inhaled sedation with sevoflurane, will be vaporized via the miniaturized Anesthesia Conserving Device (AnaConDa-S®, Sedana Medical, Uppsala, Sweden). Sevoflurane infusion rate will be adapted from manufacturer's instructions in order to reach a target of expired sevoflurane fraction (FEsevo) of 0.8-1.1. Mechanical ventilation will be protocolized in both arms, based on recent results of a RCT from our group, in which 90-day survival was improved in patients with nonfocal ARDS when an individualized ventilation strategy was applied, compared to the ARDSNet strategy (PEEP set according to FiO2). We will recommend sites wait at least 12 hours before proning, as in the PROSEVA study. In both groups, patients will receive cisatracurium besylate for neuromuscular blockade, and deep sedation will be protocolized to Richmond Agitation-Sedation Scale (RASS) of -4 to -5 (Ramsay of 5-6, or Riker of 1-2) before starting, and during, the cisatracurium besylate infusion.

Masking

Outcomes Assessor

Masking Description

It is an open label trial because the patients are included from a group depending to the morphotype of ARDS. However, all subsequent evaluations will be conducted by clinical research staff according to the attributed group

Allocation

Non-Randomized

Enrollment

43 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nonfocal ARDS

Arm Type

Experimental

Arm Description

ARDS patient with nonfocal lung imaging phenotype

Arm Title

Focal ARDS

Arm Type

Experimental

Arm Description

ARDS patient with focal lung imaging phenotype

Intervention Type

Drug

Intervention Name(s)

Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts

Intervention Description

Pharmacokinetic of inhaled sevoflurane used for sedation

Primary Outcome Measure Information:

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

5 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

30 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

1 hour after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

6 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

24 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

48 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

5 minutes after the cessation of sevoflurane administration

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

30 minutes after the cessation of sevoflurane administration

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

1 hour after the cessation of sevoflurane administration

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

4 hours after the cessation of sevoflurane administration

Title

Plasma concentrations of sevoflurane

Description

Plasma concentrations of sevoflurane

Time Frame

6 hours after the cessation of sevoflurane administration

Secondary Outcome Measure Information:

Title

Plasma concentration of hexafluoroisopropanolol

Description

Plasma concentration of hexafluoroisopropanolol

Time Frame

Until sedation can be definitely interrupted or until day 7

Title

Fraction of inspired sevoflurane

Description

Fraction of inspired sevoflurane

Time Frame

Until sedation can be definitely interrupted or until day 7

Title

Fraction of expired sevoflurane

Description

Fraction of expired sevoflurane

Time Frame

Until sedation can be definitely interrupted or until day 7

Title

Dose of sevoflurane

Description

Dose of sevoflurane (mg/l)

Time Frame

Until sedation can be definitely interrupted or until day 7

Title

Infusion duration of sevoflurane

Description

Infusion duration of sevoflurane (min)

Time Frame

Until sedation can be definitely interrupted or until day 7

Title

Infusion rate of remifentanil

Description

Infusion rate of remifentanil

Time Frame

Until sedation can be definitely interrupted or until day 7

Title

Values of a bispectral index

Description

Values of a bispectral index

Time Frame

Until sedation can be definitely interrupted or until day 7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥18 years Presence for ≤ 12 hours of all of the following conditions, within one week of a clinical insult or new or worsening respiratory symptoms : a PaO2/FiO2 < 200 mmHg with positive end-expiratory pressure (PEEP) ≥ 8 cmH2O (or, if arterial blood gas not available : SpO2/FiO2 ratio that is equivalent to a PaO2/FiO2 < 200 mmHg with PEEP ≥8 cmH2O, and a confirmatory SpO2/FiO2 ratio between 1-6 hours after the initial SpO2/FiO2 ratio determination) b Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules c 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 Exclusion Criteria: Lack of informed consent Continuous sedation with inhaled sevoflurane at enrollment Currently receiving ECMO therapy Chronic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing Body mass index > 40 kg/m2 Chronic liver disease defined as a Child-Pugh score of 12-15 Expected duration of mechanical ventilation < 48 hours Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation 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 Suspected or proven intracranial hypertension Know pregnancy - Pregnancy testing will be systematically performed to rule out pregnancy in female patients of reproductive age Enrollment in another interventional ARDS trial with direct impact on sedation and PEEP Endotracheal ventilation for greater than 120 hours (5 days) PaO2/FiO2 (if available) > 200 mmHg after meeting inclusion criteria and before start of the study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lise Laclautre

Phone

+33 73 754 963

promo_interne_drci@chu-clermontferrand.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raiko Blondonnet, MD, MSc

Organizational Affiliation

University Hospital, Clermont-Ferrand

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Jean Perrin

City

Clermont-Ferrand

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nathanael Eisenmann

Facility Name

CHU

City

Clermont-Ferrand

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Raïko Blondonnet

First Name & Middle Initial & Last Name & Degree

Russell Chabanne

First Name & Middle Initial & Last Name & Degree

Bertrand Soweine

Facility Name

APHP - University hospital of Saint-Louis

City

Paris

ZIP/Postal Code

75010

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Virginie Lemiale

virginie.lemiale@sls.aphp.fr

12. IPD Sharing Statement

Learn more about this trial

Sevoflurane PharmacokInetics in ARDS

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