Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation (INASED)
Primary Purpose
Prevention of Delirium
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Propofol + analgesic drug
Isoflurane + analgesic drug
Sponsored by
About this trial
This is an interventional treatment trial for Prevention of Delirium
Eligibility Criteria
Inclusion Criteria:
- Patient aged 18 and over
- Patient requiring mechanical ventilation for at least 24 hours
- The patient requires continuous and immediate sedation for more comfort, safety and to facilitate the administration of survival measures.
- Consent obtained from patient or relative
Exclusion Criteria:
Patient hospitalized for the following reasons for admission:
- Cardiac arrest
- State of refractory epilepticus
- Head trauma
Stroke
- Hearing, visual or aphasia disorders before inclusion making it impossible to take the CAM-ICU
- Sedation started more than 24 hours ago
- Impairment of cognitive functions and / or dementia
- Contraindication to halogenated gases (personal or family history of malignant hyperthermia, acute or chronic neuromuscular disease, hepatocellular insufficiency with PT <30%)
- Severe acute respiratory distress syndrome (ARDS) (Berlin criteria: PaO2 / FiO2 <100))
- PaCO2 at inclusion> 50 mmHg
- Patient for whom a procedure of "limitation of active therapies" is envisaged at inclusion
- Patient under guardianship or curatorship
- Minor patient
- Pregnant or breastfeeding woman
- Patient not affiliated to the social security scheme
Sites / Locations
- CH BourgesRecruiting
- CHU de BrestRecruiting
- CH Corbeil EssonnesRecruiting
- CH Le MansRecruiting
- GHBS LorientRecruiting
- CH MelunRecruiting
- CHU MontpellierRecruiting
- CH MorlaixRecruiting
- CHU PoitiersRecruiting
- CHU RennesRecruiting
- CHU ToursRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Usual sedation
Inhaled sedation
Arm Description
Sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug.
Sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA β’ associated with the administration of an analgesic drug.
Outcomes
Primary Outcome Measures
Occurrence of a delirium in intensive care
Occurrence of delirium in intensive care will be observed (yes / no)
Secondary Outcome Measures
Mortality in intensive care
Mortality in intensive care will be observed
Mortality at day 28
Mortality at day 28 will be observed
Hospital cost per patient
The average cost of hospitalization for each patient will be calculated taking into account their length of hospital stay, examinations carried out and medical treatment taken.
Number of days with vasopressors or inotropic agents
Number of days with vasopressors or inotropic agents will be observed
Number of days with sedation
Number of days with sedation will be observed
Cumulative dose anesthetics drugs
Cumulative dose anesthetics drugs will be observed
Duration of anesthetics drugs
Duration of anesthetics drugs will be observed
Maximum dose of vasopressors or inotropic agents
Maximum dose of vasopressors or inotropic agents will be observed
Ventilation free days at 28 days following randomisation
Ventilation free days at 28 days following randomisation will be observed
Incidence of delirium
Incidence of delirium will be observed
Duration of delirium
Duration of delirium will be observed
Length of ICU stay
Length of ICU stay will be calculated
Requirement of patients physical restraints
Requirement of physical restraints, of patients with unplanned extubation, unplanned catheter, urinary probe or gastric probe removal will be observed
Self aggressive act
Self aggressive act will be observed
Hetero-aggressive act
Hetero-aggressive act will be observed
Evaluation of cognitive functions
Cognitive function will be evaluated at discharge, 3- and 12 months using two kinds of score :
Cantab test, combining 6 cognitive evaluations with an iPad during a 45-60 minutes medical consultation
PCLS (Posttraumatic stress disorder Checklist Scale), HADS (Hospital Anxiety and Depression scale), SF36 (medical outcome study short form 36), IADL (instrumental activities of daily living) practised by a clinical research associate
Full Information
NCT ID
NCT04341350
First Posted
March 9, 2020
Last Updated
July 28, 2023
Sponsor
University Hospital, Brest
1. Study Identification
Unique Protocol Identification Number
NCT04341350
Brief Title
Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation
Acronym
INASED
Official Title
Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation : INASED Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 6, 2020 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
August 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Brest
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of the study is to determine the impact on the frequency of occurrence of delirium of an early inhaled sedation strategy (from induction in rapid sequence if intubation in intensive care, or from admission if intubated in pre -hospital) by Isoflurane using an ANACONDA β’ type system, compared to a conventional intravenous sedation strategy.
Detailed Description
Sedation-analgesia is used in most patients treated with mechanical ventilation (MV). The usual benzodiazepine and morphine sedation reduces pain and anxiety and allows tolerance of invasive procedures in intensive care. These molecules, used as part of the sedation titration protocol or the daily sedation stop protocol, have improved patient outcomes.
Although necessary, these drugs, by mechanisms still uncertain, would promote the occurrence of resuscitation delirium. Delirium itself responsible for worsening morbidity and mortality (increase in the duration of MV, increase in the length of hospital stay, discussed increase in mortality, long-term cognitive sequelae).
This finding favored the use of new drugs in the sedation strategies of patients on MV. Dexmedetomidine has for example reduced the number of days of delirium, the number of days of coma and even mortality in septic patients. Its large-scale use has however been questioned by a recent study.
Halogenated gases have been used for a long time in anesthesia. Their pharmacodynamics, their positive and adverse effects, their therapeutic margins are well known. Thanks to technical innovations they can be used on resuscitation respirators. Several studies on targeted populations have shown the feasibility and the benefits of this use, in particular, the absence of accumulation, the absence of tachyphylaxis, the broad therapeutic range, the small interindividual variation, the rapidity of efficacy and the speed of awakening. Safety in use for the staff in charge of the patient is established. In addition, their potential neuroprotective effect would make it an anesthetic of choice in the prevention of resuscitation delirium.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prevention of Delirium
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Usual sedation
Arm Type
Active Comparator
Arm Description
Sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug.
Arm Title
Inhaled sedation
Arm Type
Experimental
Arm Description
Sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA β’ associated with the administration of an analgesic drug.
Intervention Type
Drug
Intervention Name(s)
Propofol + analgesic drug
Intervention Description
sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug. It uses the nurse driven analgesia protocol of each ward involved in the study. It uses a pain assessment score (BPS, VICOMORE, FLACC), local or regional anesthesia, non-opioΓ―d adjuncts (acetaminophen, NSAIDs, nefopam), opioΓ―ds (per os opioΓ―ds, bolus of sufentanyl followed by continuous infusion if necessary, continuous infusion of remifentanyl
Intervention Type
Drug
Intervention Name(s)
Isoflurane + analgesic drug
Intervention Description
sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA β’ associated with the administration of a analgesic drug. It uses the nurse driven analgesia protocol of each ward involved in the study. It uses a pain assessment score (BPS, VICOMORE, FLACC), local or regional anesthesia, non-opioΓ―d adjuncts (acetaminophen, NSAIDs, nefopam), opioΓ―ds (per os opioΓ―ds, bolus of sufentanyl followed by continuous infusion if necessary, continuous infusion of remifentanyl.
Primary Outcome Measure Information:
Title
Occurrence of a delirium in intensive care
Description
Occurrence of delirium in intensive care will be observed (yes / no)
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Mortality in intensive care
Description
Mortality in intensive care will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Mortality at day 28
Description
Mortality at day 28 will be observed
Time Frame
28 days
Title
Hospital cost per patient
Description
The average cost of hospitalization for each patient will be calculated taking into account their length of hospital stay, examinations carried out and medical treatment taken.
Time Frame
Through study completion, an average of 1 year.
Title
Number of days with vasopressors or inotropic agents
Description
Number of days with vasopressors or inotropic agents will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Number of days with sedation
Description
Number of days with sedation will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Cumulative dose anesthetics drugs
Description
Cumulative dose anesthetics drugs will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Duration of anesthetics drugs
Description
Duration of anesthetics drugs will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Maximum dose of vasopressors or inotropic agents
Description
Maximum dose of vasopressors or inotropic agents will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Ventilation free days at 28 days following randomisation
Description
Ventilation free days at 28 days following randomisation will be observed
Time Frame
28 days
Title
Incidence of delirium
Description
Incidence of delirium will be observed
Time Frame
28 days
Title
Duration of delirium
Description
Duration of delirium will be observed
Time Frame
28 days
Title
Length of ICU stay
Description
Length of ICU stay will be calculated
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Requirement of patients physical restraints
Description
Requirement of physical restraints, of patients with unplanned extubation, unplanned catheter, urinary probe or gastric probe removal will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Self aggressive act
Description
Self aggressive act will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Hetero-aggressive act
Description
Hetero-aggressive act will be observed
Time Frame
Throuh exit from the intensive care unit, an average of 28 days
Title
Evaluation of cognitive functions
Description
Cognitive function will be evaluated at discharge, 3- and 12 months using two kinds of score :
Cantab test, combining 6 cognitive evaluations with an iPad during a 45-60 minutes medical consultation
PCLS (Posttraumatic stress disorder Checklist Scale), HADS (Hospital Anxiety and Depression scale), SF36 (medical outcome study short form 36), IADL (instrumental activities of daily living) practised by a clinical research associate
Time Frame
Through study completion, an average of 1 year.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient aged 18 and over
Patient requiring mechanical ventilation for at least 24 hours
The patient requires continuous and immediate sedation for more comfort, safety and to facilitate the administration of survival measures.
Consent obtained from patient or relative
Exclusion Criteria:
Patient hospitalized for the following reasons for admission:
Cardiac arrest
State of refractory epilepticus
Head trauma
Stroke
Hearing, visual or aphasia disorders before inclusion making it impossible to take the CAM-ICU
Sedation started more than 24 hours ago
Impairment of cognitive functions and / or dementia
Contraindication to halogenated gases (personal or family history of malignant hyperthermia, acute or chronic neuromuscular disease, hepatocellular insufficiency with PT <30%)
Severe acute respiratory distress syndrome (ARDS) (Berlin criteria: PaO2 / FiO2 <100 after ventilatory optimisation))
PaCO2 at inclusion> 50 mmHg after ventilatory optimisation
Patient for whom a procedure of "limitation of active therapies" is envisaged at inclusion
Patient under guardianship or curatorship
Minor patient
Pregnant or breastfeeding woman
Patient not affiliated to the social security scheme
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pierre Bailly, MD
Phone
02 98 34 71 81
Ext
+33
Email
pierre.bailly@chu-brest.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre Bailly, MD
Organizational Affiliation
CHRU Brest
Official's Role
Principal Investigator
Facility Information:
Facility Name
CH Bourges
City
Bourges
ZIP/Postal Code
18000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Catherine BESSE, MD
Email
marie-catherine.besse@ch-bourges.fr
Facility Name
CHU de Brest
City
Brest
ZIP/Postal Code
29200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Bailly, MD
Phone
02 98 34 71 81
Ext
+33
Email
pierre.bailly@chu-brest.fr
Facility Name
CH Corbeil Essonnes
City
Corbeil-Essonnes
ZIP/Postal Code
91106
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Billiou Cecilia, MD
Phone
0161693519
Email
cecilia.billiou@chsf.fr
Facility Name
CH Le Mans
City
Le Mans
ZIP/Postal Code
72039
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe GUITTON, Dr
Phone
02 53 04 04 42
Ext
+33
Email
cguitton@ch-lemans.fr
Facility Name
GHBS Lorient
City
Lorient
ZIP/Postal Code
56322
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillaume GRILLET, Dr
Email
g.grillet@ghbs.bzh
Facility Name
CH Melun
City
Melun
ZIP/Postal Code
77000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandie MAZERAND, MD
Phone
0181742641
Ext
+33
Email
sandie.mazerand@ghsif.fr
Facility Name
CHU Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samir JABER, Dr
Phone
04 67 33 72 71
Ext
+33
Email
s-jaber@chu-montpellier.fr
Facility Name
CH Morlaix
City
Morlaix
ZIP/Postal Code
29672
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre-Yves EGRETEAU, Dr
Phone
02 98 62 60 95
Ext
+33
Email
pyegreteau@ch-morlaix.fr
Facility Name
CHU Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnaud THILLE, Pr
Phone
05 49 44 43 67
Ext
+33
Email
arnaud.thille@chu-poitiers.fr
Facility Name
CHU Rennes
City
Rennes
ZIP/Postal Code
35033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florian REIZINE, Dr
Email
florian.reizine@chu-rennes.fr
Facility Name
CHU Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan EHRMANN, Pr
Phone
06 71 10 33 02
Ext
+33
Email
stephan.ehrmann@univ-tours.fr
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All collected data that underlie results in a publication
IPD Sharing Time Frame
Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
IPD Sharing Access Criteria
Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
Citations:
PubMed Identifier
33608400
Citation
Bailly P, Egreteau PY, Ehrmann S, Thille AW, Guitton C, Grillet G, Reizine F, Huet O, Jaber S, Nowak E, L'her E. Inased (inhaled sedation in ICU) trial protocol: a multicentre randomised open-label trial. BMJ Open. 2021 Feb 19;11(2):e042284. doi: 10.1136/bmjopen-2020-042284.
Results Reference
derived
Learn more about this trial
Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation
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