Sevoflurane PharmacokInetics in ARDS

NCT ID: NCT04023305

Last Updated: 2023-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-23

Study Completion Date

2022-01-01

Brief Summary

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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

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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.

Conditions

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Acute Respiratory Distress Syndrome

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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

Study Groups

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Nonfocal ARDS

ARDS patient with nonfocal lung imaging phenotype

Group Type EXPERIMENTAL

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

Intervention Type DRUG

Pharmacokinetic of inhaled sevoflurane used for sedation

Focal ARDS

ARDS patient with focal lung imaging phenotype

Group Type EXPERIMENTAL

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

Intervention Type DRUG

Pharmacokinetic of inhaled sevoflurane used for sedation

Interventions

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

Pharmacokinetic of inhaled sevoflurane used for sedation

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Clermont-Ferrand

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raiko Blondonnet, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Locations

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Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

CHU

Clermont-Ferrand, , France

Site Status

APHP - University hospital of Saint-Louis

Paris, , France

Site Status

Countries

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France

Other Identifiers

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2018-003511-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPIDERMAN Study

Identifier Type: -

Identifier Source: org_study_id