Sevoflurane PharmacokInetics in ARDS

NCT04023305 | Terminated

• 2 other identifiers: SPIDERMAN Study2018-003511-21
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (11)

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

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

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

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

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

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

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

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

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

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

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

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

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

  5 minutes after the cessation of sevoflurane administration

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

  30 minutes after the cessation of sevoflurane administration

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

  1 hour after the cessation of sevoflurane administration

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

  4 hours after the cessation of sevoflurane administration

• Plasma concentrations of sevoflurane

  Plasma concentrations of sevoflurane

  6 hours after the cessation of sevoflurane administration

Secondary Outcomes (7)

• Plasma concentration of hexafluoroisopropanolol

  Until sedation can be definitely interrupted or until day 7

• Fraction of inspired sevoflurane

  Until sedation can be definitely interrupted or until day 7

• Fraction of expired sevoflurane

  Until sedation can be definitely interrupted or until day 7

• Dose of sevoflurane

  Until sedation can be definitely interrupted or until day 7

• Infusion duration of sevoflurane

  Until sedation can be definitely interrupted or until day 7

Study Arms (2)

Nonfocal ARDS

EXPERIMENTAL

ARDS patient with nonfocal lung imaging phenotype

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

Focal ARDS

EXPERIMENTAL

ARDS patient with focal lung imaging phenotype

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

Interventions

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

Pharmacokinetic of inhaled sevoflurane used for sedation

Focal ARDS; Nonfocal ARDS

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (3)

Centre Jean Perrin

Clermont-Ferrand, France

Location

CHU

Clermont-Ferrand, France

Location

APHP - University hospital of Saint-Louis

Paris, 75010, France

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Raiko Blondonnet, MD, MSc

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 17, 2019
• Study Start: February 23, 2020
• Primary Completion: December 1, 2021
• Study Completion: January 1, 2022
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

FR (3)