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Sevoflurane PharmacokInetics in ARDS (SPIDERMAN)

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ClinicalTrials.gov Identifier: NCT04023305
Recruitment Status : Not yet recruiting
First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

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.

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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: Single (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
Primary Purpose: Treatment
Official Title: Sevoflurane pharmacokInetics During Inhaled Sedation Relies on the Morphotype of ARDS in ICU Patients
Estimated Study Start Date : August 31, 2019
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Nonfocal ARDS
ARDS patient with nonfocal lung imaging phenotype
Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts
Pharmacokinetic of inhaled sevoflurane used for sedation

Experimental: Focal ARDS
ARDS patient with focal lung imaging phenotype
Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts
Pharmacokinetic of inhaled sevoflurane used for sedation




Primary Outcome Measures :
  1. Plasma concentrations of sevoflurane [ Time Frame: 5 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit ]
    Plasma concentrations of sevoflurane

  2. Plasma concentrations of sevoflurane [ Time Frame: 30 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit ]
    Plasma concentrations of sevoflurane

  3. Plasma concentrations of sevoflurane [ Time Frame: 1 hour after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit ]
    Plasma concentrations of sevoflurane

  4. Plasma concentrations of sevoflurane [ Time Frame: 6 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit ]
    Plasma concentrations of sevoflurane

  5. Plasma concentrations of sevoflurane [ Time Frame: 24 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit ]
    Plasma concentrations of sevoflurane

  6. Plasma concentrations of sevoflurane [ Time Frame: 48 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit ]
    Plasma concentrations of sevoflurane

  7. Plasma concentrations of sevoflurane [ Time Frame: 5 minutes after the cessation of sevoflurane administration ]
    Plasma concentrations of sevoflurane

  8. Plasma concentrations of sevoflurane [ Time Frame: 30 minutes after the cessation of sevoflurane administration ]
    Plasma concentrations of sevoflurane

  9. Plasma concentrations of sevoflurane [ Time Frame: 1 hour after the cessation of sevoflurane administration ]
    Plasma concentrations of sevoflurane

  10. Plasma concentrations of sevoflurane [ Time Frame: 4 hours after the cessation of sevoflurane administration ]
    Plasma concentrations of sevoflurane

  11. Plasma concentrations of sevoflurane [ Time Frame: 6 hours after the cessation of sevoflurane administration ]
    Plasma concentrations of sevoflurane


Secondary Outcome Measures :
  1. Plasma concentration of hexafluoroisopropanolol [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Plasma concentration of hexafluoroisopropanolol

  2. Fraction of inspired sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Fraction of inspired sevoflurane

  3. Fraction of expired sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Fraction of expired sevoflurane

  4. Dose of sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Dose of sevoflurane (mg/l)

  5. Infusion duration of sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Infusion duration of sevoflurane (min)

  6. Infusion rate of remifentanil [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Infusion rate of remifentanil

  7. Values of a bispectral index [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]
    Values of a bispectral index



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04023305


Contacts
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Contact: Lise Laclautre +33 73 754 963 promo_interne_drci@chu-clermontferrand.fr

Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
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Principal Investigator: Raiko Blondonnet, MD, MSc University Hospital, Clermont-Ferrand

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Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT04023305     History of Changes
Other Study ID Numbers: SPIDERMAN Study
2018-003511-21 ( EudraCT Number )
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Clermont-Ferrand:
Nonfocal Acute respiratory distress syndrome
Focal Acute respiratory distress syndrome
Sevoflurane
Pharmacokinetics
Mechanical ventilation
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Syndrome
Respiratory Tract Diseases
Infant, Newborn, Diseases
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiration Disorders
Infant, Premature, Diseases
Lung Injury
Sevoflurane
Platelet Aggregation Inhibitors
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs