免费获得国外相关药品，最快 1 个工作日回馈药物信息
Sevoflurane PharmacokInetics in ARDS (SPIDERMAN)
| 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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 43 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 |
| Actual Study Start Date : | February 23, 2020 |
| Estimated Primary Completion Date : | March 1, 2023 |
| Estimated Study Completion Date : | June 1, 2023 |
| 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
|
- 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
- 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
- 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
- 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
- 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
- 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
- Plasma concentrations of sevoflurane [ Time Frame: 5 minutes after the cessation of sevoflurane administration ]Plasma concentrations of sevoflurane
- Plasma concentrations of sevoflurane [ Time Frame: 30 minutes after the cessation of sevoflurane administration ]Plasma concentrations of sevoflurane
- Plasma concentrations of sevoflurane [ Time Frame: 1 hour after the cessation of sevoflurane administration ]Plasma concentrations of sevoflurane
- Plasma concentrations of sevoflurane [ Time Frame: 4 hours after the cessation of sevoflurane administration ]Plasma concentrations of sevoflurane
- Plasma concentrations of sevoflurane [ Time Frame: 6 hours after the cessation of sevoflurane administration ]Plasma concentrations of sevoflurane
- Plasma concentration of hexafluoroisopropanolol [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Plasma concentration of hexafluoroisopropanolol
- Fraction of inspired sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Fraction of inspired sevoflurane
- Fraction of expired sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Fraction of expired sevoflurane
- Dose of sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Dose of sevoflurane (mg/l)
- Infusion duration of sevoflurane [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Infusion duration of sevoflurane (min)
- Infusion rate of remifentanil [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Infusion rate of remifentanil
- Values of a bispectral index [ Time Frame: Until sedation can be definitely interrupted or until day 7 ]Values of a bispectral index
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
| Contact: Lise Laclautre | +33 73 754 963 | promo_interne_drci@chu-clermontferrand.fr |
| France | |
| Centre Jean Perrin | Recruiting |
| Clermont-Ferrand, France | |
| Contact: Nathanael Eisenmann | |
| CHU | Recruiting |
| Clermont-Ferrand, France | |
| Contact: Raïko Blondonnet | |
| Sub-Investigator: Russell Chabanne | |
| Sub-Investigator: Bertrand Soweine | |
| APHP - University hospital of Saint-Louis | Not yet recruiting |
| Paris, France, 75010 | |
| Contact: Virginie Lemiale virginie.lemiale@sls.aphp.fr | |
| Principal Investigator: | Raiko Blondonnet, MD, MSc | University Hospital, Clermont-Ferrand |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | July 10, 2019 | ||||
| First Posted Date ICMJE | July 17, 2019 | ||||
| Last Update Posted Date | May 18, 2021 | ||||
| Actual Study Start Date ICMJE | February 23, 2020 | ||||
| Estimated Primary Completion Date | March 1, 2023 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
|
||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
|
||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Sevoflurane PharmacokInetics in ARDS | ||||
| Official Title ICMJE | Sevoflurane pharmacokInetics During Inhaled Sedation Relies on the Morphotype of ARDS in ICU Patients | ||||
| 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. |
||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Not Applicable | ||||
| Study Design ICMJE | 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 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
|
||||
| Condition ICMJE | Acute Respiratory Distress Syndrome | ||||
| Intervention ICMJE | Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts
Pharmacokinetic of inhaled sevoflurane used for sedation
|
||||
| Study Arms ICMJE |
|
||||
| Publications * | Not Provided | ||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
43 | ||||
| Original Estimated Enrollment ICMJE |
30 | ||||
| Estimated Study Completion Date ICMJE | June 1, 2023 | ||||
| Estimated Primary Completion Date | March 1, 2023 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
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:
|
||||
| Sex/Gender ICMJE |
|
||||
| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
|
||||
| Listed Location Countries ICMJE | France | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT04023305 | ||||
| Other Study ID Numbers ICMJE | SPIDERMAN Study 2018-003511-21 ( EudraCT Number ) |
||||
| Has Data Monitoring Committee | Not Provided | ||||
| U.S. FDA-regulated Product |
|
||||
| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | University Hospital, Clermont-Ferrand | ||||
| Study Sponsor ICMJE | University Hospital, Clermont-Ferrand | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
|
||||
| PRS Account | University Hospital, Clermont-Ferrand | ||||
| Verification Date | May 2021 | ||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||
