Comparison of an inhaled sedation strategy with an intravenous sedation strategy in intensive care patients treated with invasive mechanical ventilation: INASED study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Et Universitaire De Brest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

9 Aug 2024 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513530-37-00

EudraCT number

2019-004537-16

ClinicalTrials.gov

NCT04341350

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Determine the impact on the frequency of delirium occurrence of an early inhaled sedation strategy (from induction in rapid sequence if intubated in the ICU, or from admission if intubated in the pre-hospital setting) with Isoflurane using an ANACONDA™-type system, compared with a conventional intravenous sedation strategy.

Secondary objectives 14

1. Determine ICU morbidity and mortality
2. Determine length of stay in intensive care unit and number of days without intensive care at D28
3. Determine the number of days without mechanical ventilation
4. Determine the incidence of delirium after weaning from sedation
5. Determine quality of sedation (compliance with target-based prescribing)
6. Determine safety of use (hemodynamic, hepatic, renal, etc.)
7. Determining Dosages of vasopressor amines, vascular filling and the need for renal replacement will be systematically collated.
8. Determine the incidence of agitation requiring additional prescription medication
9. Determine the rate of physical restraint (excluding hand restraint, if service protocol)
10. Determine rate of self-extubation and catheter or probe removal
11. Determine rate of self- or hetero-aggressions
12. Determine long-term cognitive, psychological and quality-of-life consequences
13. Determine the efficacy of sedation in a specific subgroup of patients who are "difficult to sedate": excessive alcohol consumption (SFA consensus definition), long-term psychotropic treatment, unweaned drug addiction or on drug replacement therapy.
14. Determine the economic value of the Isoflurane inhalation sedation strategy

Conditions and MedDRA coding

Delirium

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patient aged 18 and over
2. Patient requires mechanical ventilation for at least 24 hours
3. Patient requires immediate continuous sedation for comfort, safety and to facilitate the administration of life-sustaining measures.
4. Consent obtained from patient or relative

Exclusion criteria 12

1. Patient admitted for the following reasons : - Cardiac arrest - Refractory status epilepticus - Moderate to severe head trauma - Cerebrovascular accident
2. Auditory or visual impairment, or aphasia prior to inclusion, making CAM-ICU impossible to perform
3. Sedation for more than 24 hours
4. Impaired cognitive function and/or dementia
5. Contraindication to halogenated gas (personal or family history of malignant hyperthermia, acute or chronic neuromuscular disease, hepatocellular insufficiency with TP<30%)
6. Severe ARDS (Berlin criteria: PaO2/FiO2<100 after ventilatory optimization)
7. PaCO2 at inclusion > 50 mmHg with pH<7.2 after ventilatory optimization
8. Patient for whom a "limitation of active therapies" procedure is envisaged on inclusion
9. Patient under guardianship or curatorship
10. Minors
11. Pregnant or breast-feeding women
12. Patient not affiliated to the social security system

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence (yes/no) of delirium in intensive care unit

Secondary endpoints 12

1. ICU mortality, D28 mortality
2. - Length of stay in intensive care
3. - Number of days living without mechanical ventilation in intensive care at D28
4. - CAM-ICU scale (2 times/day)
5. - The quality of sedation is defined by: compliance (yes/no) with the sedation target (sedation score set as the target when prescribing)
6. - Need for additional medication to alleviate agitation (yes/no, and if yes neuroleptic, benzodiazepine, dexmedetomidine)
7. - Need for additional physical restraint to alleviate a state of agitation (yes/no)
8. - Number of accidental removals by the patient of intubation tubes, vascular access tubes, nasogastric tubes and urinary catheters, based on the number of days in intensive care.
9. - Number of self- or hetero-aggressive acts per number of days in intensive care
10. - Average hospital costs per patient
11. - Daily and cumulative dose of sedative
12. - Cognitive consequences will be assessed. Calculation of CDR and IQCODE scores. Cognitive, psychological and quality of life assessment at 3 and 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Et Universitaire De Brest

Sponsor organisation

Centre Hospitalier Regional Et Universitaire De Brest

Address

2 Avenue Marechal Foch

City

Brest

Postcode

29200

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Clinical trial project manager

Public contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Clinical trial project manager

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications