Inhaled sedation in the critically ill patient

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Universitario La Paz

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

17 Oct 2025 → ongoing

Decision date (initial)

2025-03-14

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the days free of mechanical ventilation in patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients in whom more than 48 hours of invasive mechanical ventilation are expected.

Secondary objectives 8

1. To compare the days free of stay in the ICU in patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients in whom more than 48 hours of invasive mechanical ventilation are expected.
2. To compare the time to extubation after withdrawal of sedation between patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol.
3. To compare the effectiveness of sedation in maintaining a target level of sedation between patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol.
4. Compare the percentage of patients requiring one or more additional hypnotics in the inhaled sedation group versus the intravenous sedation with propofol group to maintain the target RASS.
5. To compare the incidence and duration of delirium between patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol.
6. To compare mortality at 60 days from randomization between critically ill patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol.
7. To assess mental and cognitive status 90 days after hospital discharge among patients who received sedation with isoflurane versus those who received intravenous sedation with propofol.
8. To compare the time to awakening (RASS between -1 and +1) after sedation withdrawal between patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol.

Conditions and MedDRA coding

Critical condition

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age equal to or greater than 18 years
2. Mechanically ventilated patients in whom a minimum mechanical ventilation time of 48 hours from randomization is expected.
3. Patients in whom it is necessary to maintain a RASS between -3 and -5.

Exclusion criteria 18

1. Contraindication for isoflurane or propofol.
2. Patients with extracorporeal CO2 extraction system (ECCO2R).
3. Critical burn patients.
4. Patients admitted due to recovered cardiorespiratory arrest.
5. History of ventricular tachycardia/long QT syndrome.
6. Patients who have remained on mechanical ventilation for more than 48 hours at the time of randomization.
7. Tidal volume less than 300 ml or PaCO2 greater than 50 mm Hg at the time of randomization.
8. Pregnancy.
9. History of allergy or intolerance to isoflurane.
10. Acute neurological pathology (head trauma, intraparenchymal hemorrhage, subarachnoid hemorrhage or post-operative neurosurgery).
11. Any type of disorder (blindness, deafness, dementia) or language barrier that prevents the completion of the scales for the assessment of delirium or cognitive assessment.
12. Life expectancy of less than 48 hours or patients with such a level of severity that death during admission to the ICU is considered highly probable.
13. Patients in whom repeated surgical interventions are expected during their stay in the ICU.
14. Patients with extracorporeal oxygenation system (ECMO).
15. Mandatory need for active humidification.
16. Need for benzodiazepine use due to a specific indication (e.g., withdrawal syndrome).
17. Neuromuscular disease or high spinal cord injury that may prevent weaning from mechanical ventilation due to baseline condition.
18. Lack of informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean number of days free of mechanical ventilation at day 28 from randomization.

Secondary endpoints 11

1. Mean number of days free of ICU stay on day 28 from randomization.
2. Average number of hours until extubation after withdrawal of sedation evaluated on the day of withdrawal or on day 28, whichever occurs first, from randomization.
3. Average RASS scale score maintained during the sedation maintenance period by participants in both treatment arms.
4. Proportion of participants that require the additon one or more hypnotics.
5. Proportion of participants with delirium on day 28 and average number of days with delirium on day 28 (assessed using the CAM-ICU scale).
6. Proportion of participants who died from any cause until day 60 from randomization.
7. Proportion of participants with symptoms of anxiety, depression or post-traumatic stress disorder 90 days after hospital discharge.
8. Proportion of patients who present an abnormal score in the cognitive assessment 90 days after hospital discharge.
9. Proportion of patients presenting adverse reactions in both arms.
10. Average number of hours to awakening (RASS range from -1 to +1) after sedation withdrawal.
11. Proportion of patients with abnormal scores on functional activity assessment (Barthel Index) at 90 days after hospital discharge.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Universitario La Paz

Sponsor organisation

Hospital Universitario La Paz

Address

Paseo De La Castellana 261

City

Madrid

Postcode

28046

Country

Spain

Scientific contact point

Organisation

Hospital Universitario La Paz

Contact name

José Manuel Añón Elizalde

Public contact point

Organisation

Hospital Universitario La Paz

Contact name

José Manuel Añón Elizalde

Locations

1 EU/EEA country · 28 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 8 files

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

Application history

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