SedationPhase 4IS-CRITICNCT07000526
Inhaled Sedation in Critically Ill Patients
A Phase 4 study testing Isoflurane and Propofol in people with Sedation and Airway Extubation, run by Instituto de Investigación Hospital Universitario La Paz at 22 sites in Spain.
Trial summary
The proposal of this study is to compare inhaled sedation with isoflurane administered via the Sedaconda ACD-S system with intravenous sedation with propofol. Patients will be randomized 1:1 to receive either inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden)… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sedation, Airway Extubation
- What is being tested?
- Isoflurane and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 620 participants
- Where
- 22 sitesSpain
- Study dates
- 15 Dec 2025to Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients receiving mechanical ventilation, with an anticipated duration >48 hours after randomization, and requiring deep sedation (target RASS between -3 and -5).
Who cannot join
- Contraindication to isoflurane or propofol
- Patients with maternal ancestry from Venezuela, due to the potential presence of an mt-ND4 gene mutation associated with neurological injury after exposure to certain volatile anaesthetic agents
- Significant air leak, defined as a leak exceeding 30% of the delivered minute ventilation
- Allergy to isoflurane or propofol
- Cardiopulmonary arrest
- History of ventricular tachycardia or long QT syndrome
Show all 21Show fewer
- Tidal volume < 300 mL or PaCO₂ > 50 mmHg at the time of randomization.
- Invasive mechanical ventilation for more than 48 hours at the time of randomization.
- Pregnancy
- Breast feeding
- Acute neurological condition
- Patients expected to require repeated surgical interventions during their ICU stay.
- ECMO
- ECCO2R
- Active humidification strictly required
- Neuromuscular disease or high spinal cord injury likely to prevent discontinuation of mechanical ventilation due to baseline condition
- Requirement for benzodiazepine use for a specific indication
- Burns
- Life expectancy less than 48 hours, or patients with such a level of severity that death during the ICU stay is considered highly likely.
- Any condition (e.g., blindness, deafness, dementia) or language barrier that prevents the administration of delirium or cognitive assessment scales.
- Lack of informed consent
Trial locations and contacts
22 sites in 1 country. Contact the study team or a site near you to ask about taking part.
22 sites in 1 country
Spain22 sites, 22 recruiting
- Not yet recruiting
Hospital Universitario de Albacete
Albacete
Jose M. Gutierrez, gutoman67@gmail.com
José M. Gutierrez, MD
- Not yet recruiting
Hospital Universitario Doctor José Molina Orosa
Arrecife, Lanzarote-Canary Islands, 35500
Andoni García-Muñoz, MD, andogarcia90@hotmail.com
Andoni García-Muñoz, MD
- Recruiting
Hospital Germans Trias i Pujol
Badalona
Paula Pedreira, paupedreira@gmail.com
Paula Pedreira, MD
- Recruiting
Hospital Universitario de Bellvitge
Barcelona
Paola Cardenas, pcardenas@bellvitgehospital.cat
Paola Cardenas, MD
- Recruiting
Hospital Universitario Valle de Hebron
Barcelona
Raquel S. Contreras, MD, raquelsofia.contreras@vallhebron.cat
Raquel S. Contreras, MD
- Not yet recruiting
Hospital Galdakao-Usansolo Ospitalea
Galdakao, Vizcaya
Iraia Arbelaiz, MD, IRAIA.ARBELAIZBELTRAN@osakidetza.eus
Iraia Arbelaiz, MD
- Not yet recruiting
Hospital Universitario de Jaen
Jaén
Miguel A Fernández-Sacristan, MD, mafsacristan@gmail.com
Miguel A Fernández-Sacristan, MD
- Not yet recruiting
Hospital Arnau de Vilanova
Lleida
Jesús Caballero, MD, PhD, jcaballero.lleida.ics@gencat.cat
Jesús Caballero, MD, PhD
- Not yet recruiting
Hospital Universitario de Fuenlabrada
Madrid, 28029
Carmen C Sena-Pérez, MD, carmencarolina.sena@salud.madrid.org
Carmen C Sena-Pérez, MD
- Recruiting
Hospital Universitario La Paz
Madrid, 28029
José M Añón, MD, PhD, josem.anon@salud.madrid.org
José M Añón, MD, PhD
- Not yet recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28029
José Antonio Marquez, MD, joseantoniomarquezalonso@gmail.com
José Antonio Marquez, MD
- Not yet recruiting
Hospital Univeritario Puerta de Hierro
Madrid
Miguel Angel Romera, MD,PhD, miguelangel.romera@salud.madrid.org
Miguel Angel Romera, MD
- Recruiting
Hospital Universitario de la Princesa
Madrid
Aris Perez Lucendo, MD, aris.perezlucendo@gmail.com
Aris Perez Lucendo, MD
- Recruiting
Hospital Universitario Gregorio Marañon
Madrid
José M. Gomez, MD, semagomezgarcia@hotmail.com
José M. Gomez, MD
- Recruiting
Hospital Universitario Infanta Leonor
Madrid
María Paz Escuela, MD, PhD, mpescuela@gmail.com
María Paz Escuela, MD, PhD
- Recruiting
Hospital Universitario Rey Juan Carlos
Madrid
Manuel Pérez Torres, manuel.ptorres@hospitalreyjuancarlos.es
Manuel Perez Torres, MD
- Not yet recruiting
Hospital Regional Universitario de Málaga
Málaga
Guillermo Gomez, MD, guigoga1286@gmail.com
Guillermo Gomez, MD
- Recruiting
Hospital Vega Baja
Orihuela, Alicante
Carola Gimenez-Esparza, MD, carolagimenezesparzavich@gmail.com
Carola Gimenez-Esparza, MD
- Recruiting
Hospital Universitario Joan XXIII
Tarragona
Oriol Plans, oplans.hj23.ics@gencat.cat
Oriol Plans, MD
- Not yet recruiting
Hospital Universitario de Toledo
Toledo
Mario Dalorzo, mardago31@gmail.com
Mario Dalorzo, MD
- Recruiting
Hospital Clínico Universitario de Valencia
Valencia
Monica García Simon, MD, mgs11122002@yahoo.es
Monica García Simón, MD
- Recruiting
Hospital Universitario Rio Hortega
Valladolid
Ana Prieto, amprietolamo@gmail.com
Ana Prieto, MD
About this study
Official title: Inhaled Sedation in Critically Ill Patients: a Multicentre Randomized Clinical Trial
The proposal of this study is to compare inhaled sedation with isoflurane administered via the Sedaconda ACD-S system with intravenous sedation with propofol. Patients will be randomized 1:1 to receive either inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous propofol. The primary endpoint is the number of ventilator-free days at 28 days after randomization.
Read the detailed description
Justification: Isoflurane has recently emerged as an attractive alternative for intensive care unit (ICU) sedation. Due to their favorable pharmaco-kinetic and dynamic profile, this agent has been progressively introduced into clinical practice. Isoflurane has proven to be non-inferior to propofol in terms of efficacy and safety and it has been suggested that it may facilitate ventilator weaning. However, no differences in length of mechanical ventilation were found. These studies have focused on short sedation durations. In fact, long-term effects and outcomes associated with isoflurane for ICU sedation are not yet fully understood.
Hypothesis: Inhaled sedation with isoflurane administered via the Sedaconda ACD-S system in critically ill patients leads to a shorter duration of mechanical ventilation at 28 days and a reduced length of ICU stay compared to intravenous sedation with propofol.
Main objective: To compare the number of ventilator-free days at day 28 post-randomization between critically ill patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients expected to require more than 48 hours of invasive mechanical ventilation. Key secondary objective: To compare the number of ICU-free days at day 28 post-randomization in both treatment arms. Secondary objectives: To compare time to extubation after sedation withdrawal, efficacy in maintaining a target level of sedation, compare the percentage of patients requiring one or more additional hypnotics, compare the incidence and duration of delirium at day 28, assess mental, cognitive, and quality of life status at 90 days post-hospital discharge between both treatment groups.
Methodology: Phase IV, low-intervention, open-label, multicenter, randomized controlled trial with intention-to-treat analysis including mechanically ventilated patients expected to require a minimum of 48 hours of mechanical ventilation with a RASS score between -3 and -5. Patients will be randomized 1:1 to receive inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous sedation with propofol. A total of 620 patients will be included from a pool of 22 participating centers.
- Conditions
- Sedation, Airway Extubation
- Being tested
- Isoflurane, Propofol
- Keywords
- Inhaled sedation, Mechanical ventilation, Delirium
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsofluraneDrug
Also called Inhaled sedation with Isoflurane
Inhaled sedation with isoflurane via Sedaconda ACD-S
PropofolDrug
Also called Intravenous sedation with Propofol
Intravenous sedation with Propofol 20 mg/ml
| Study group | Role | What they receive |
|---|---|---|
| Study group | Experimental | Inhaled sedation with Isoflurane. Initial dose: 3 mL/h. Gradual dose increase until target RASS is achieved. Do not exceed 14 mL/h. Guided by end tidal isoflurane concentration (EtISO), the recommended maximum dose for prolonged use is 1%. Short periods at up to 1.5% may be considered. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added. Receives: Drug: Isoflurane |
| Control group | Active comparator | Intravenous sedation with propofol (20 mg/mL). Initial dose: 0.5-1 mg/kg/h. Gradual dose increase until target RASS is achieved. Do not exceed 4 mg/kg/h. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added. Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventilator-free days at day 28 from randomization
Number of days between randomization and day 28 during which the patient is alive and free from invasive mechanical ventilation. Patients who die before day 28, or who remain on mechanical ventilation at day 28, are assigned zero ventilator-free days.
Measured: From randomization until day 28
Secondary outcomes (9)
Key secondary objective: ICU-free days at day 28 post-randomization
Number of days between randomization and day 28 during which the patient is alive and free from the ICU. Patients who die before day 28, or remain in the ICU on day 28, are assigned zero ICU-free days.
Measured: From randomization until day 28
Time to extubation
Mean number of hours from sedation withdrawal to successful extubation.
Measured: From randomization until day 28
Administration of rescue sedation
Number of patients requiring the addition of one or more hypnotics
Measured: From randomization until day 28
Sedation efficacy
Difference between the target sedation level and the actual measured level using Richmond Agitation Sedation Scale (RASS). Possible RASS score ranges from -5 (unarousable) to +4 (combative)
Measured: From randomization until extubation or day 28
Number of Participants With Delirium
Number of patients with delirium using the Confusion Assessment Method in ICU (CAM-ICU)
Measured: From randomization until extubation or day 28
Mortality
All cause mortality at 60 days from randomization
Measured: From randomization to day 60
Number of Participants With Psychological disorders
Psychological status assessed using: 1.- Hospital Anxiety and Depression Scale (HADS). score of 8 or greater on the anxiety or depression subscale is used to identify symptoms of clinically significant anxiety or depression. 2.- Impact of Event Scale - Revised (IES-R), a self-report measure designed to assess the severity of post-traumatic stress disorder. Optimal screening threshold established as 1.6 (Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med 2020)
Measured: at 90 days of hospital discharge
Number of Participants With Cognitive Disorders
Cognitive status assessed using Montreal Cognitive Assessment (MoCA) test. Total score ranges from zero to 30. Mild cognitive impairment: 18-25, moderate: 10-17, and severe: less than 10 (Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med 2020)
Measured: at 90 days of hospital discharge
Number of Participants With Treatment-Related Adverse Events
Number of participants who experience at least one adverse event of special interest, deemed by the investigators to be related to the administered hypnotic, including events of mild, moderate, severe intensity, as well as serious adverse events
Measured: From randomization to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2025
- Study start15 Dec 2025
- Primary completionMar 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SedationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 620 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Hospital Universitario La Paz
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III
- Responsible party
- Principal investigator, José Manuel Añón, Instituto de Investigación Hospital Universitario La Paz
- Investigators
- José M. Añón, MD, PhD, Principal investigator, Hospital Universitario La Paz. IdiPAZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07000526
- Sponsor's protocol ID
- HULP6844
- Other IDs
- 2024-518521-14-00
- Acronym
- IS-CRITIC
- Status last verified
- Jun 2026
- First submitted
- 22 May 2025
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Sedation in Critically Ill Patients: a Multicentre Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07000526
- Acronym / sponsor ID
- IS-CRITIC / HULP6844
- Conditions
- Sedation, Airway Extubation
- Keywords
- Inhaled sedation, Mechanical ventilation, Delirium
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 620 participants (estimated)
- Lead sponsor
- Instituto de Investigación Hospital Universitario La PazUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III
- Study start
- 15 Dec 2025 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 3 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposal of this study is to compare inhaled sedation with isoflurane administered via the Sedaconda ACD-S system with intravenous sedation with propofol. Patients will be randomized 1:1 to receive either inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous propofol. The primary endpoint is the number of ventilator-free days at 28 days after randomization.
Detailed description
Justification: Isoflurane has recently emerged as an attractive alternative for intensive care unit (ICU) sedation. Due to their favorable pharmaco-kinetic and dynamic profile, this agent has been progressively introduced into clinical practice. Isoflurane has proven to be non-inferior to propofol in terms of efficacy and safety and it has been suggested that it may facilitate ventilator weaning. However, no differences in length of mechanical ventilation were found. These studies have focused on short sedation durations. In fact, long-term effects and outcomes associated with isoflurane for ICU sedation are not yet fully understood.
Hypothesis: Inhaled sedation with isoflurane administered via the Sedaconda ACD-S system in critically ill patients leads to a shorter duration of mechanical ventilation at 28 days and a reduced length of ICU stay compared to intravenous sedation with propofol.
Main objective: To compare the number of ventilator-free days at day 28 post-randomization between critically ill patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients expected to require more than 48 hours of invasive mechanical ventilation. Key secondary objective: To compare the number of ICU-free days at day 28 post-randomization in both treatment arms. Secondary objectives: To compare time to extubation after sedation withdrawal, efficacy in maintaining a target level of sedation, compare the percentage of patients requiring one or more additional hypnotics, compare the incidence and duration of delirium at day 28, assess mental, cognitive, and quality of life status at 90 days post-hospital discharge between both treatment groups.
Methodology: Phase IV, low-intervention, open-label, multicenter, randomized controlled trial with intention-to-treat analysis including mechanically ventilated patients expected to require a minimum of 48 hours of mechanical ventilation with a RASS score between -3 and -5. Patients will be randomized 1:1 to receive inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous sedation with propofol. A total of 620 patients will be included from a pool of 22 participating centers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study group | Experimental | Drug: IsofluraneInhaled sedation with Isoflurane. Initial dose: 3 mL/h. Gradual dose increase until target RASS is achieved. Do not exceed 14 mL/h. Guided by end tidal isoflurane concentration (EtISO), the recommended maximum dose for prolonged use is 1%. Short periods at up to 1.5% may be considered. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added. |
| Control group | Active comparator | Drug: PropofolIntravenous sedation with propofol (20 mg/mL). Initial dose: 0.5-1 mg/kg/h. Gradual dose increase until target RASS is achieved. Do not exceed 4 mg/kg/h. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients receiving mechanical ventilation, with an anticipated duration >48 hours after randomization, and requiring deep sedation (target RASS between -3 and -5).
Key exclusion criteria (21 listed)
- Contraindication to isoflurane or propofol
- Patients with maternal ancestry from Venezuela, due to the potential presence of an mt-ND4 gene mutation associated with neurological injury after exposure to certain volatile anaesthetic agents
- Significant air leak, defined as a leak exceeding 30% of the delivered minute ventilation
- Allergy to isoflurane or propofol
- Cardiopulmonary arrest
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsofluraneAlso: Inhaled sedation with IsofluraneInhaled sedation with isoflurane via Sedaconda ACD-S | Drug | Study group |
| PropofolAlso: Intravenous sedation with PropofolIntravenous sedation with Propofol 20 mg/ml | Drug | Control group |
Primary outcome
Ventilator-free days at day 28 from randomization
Time frame: From randomization until day 28
Number of days between randomization and day 28 during which the patient is alive and free from invasive mechanical ventilation. Patients who die before day 28, or who remain on mechanical ventilation at day 28, are assigned zero ventilator-free days.
9 secondary outcomes
Key secondary objective: ICU-free days at day 28 post-randomization
Time frame: From randomization until day 28
Time to extubation
Time frame: From randomization until day 28
Administration of rescue sedation
Time frame: From randomization until day 28
Sedation efficacy
Time frame: From randomization until extubation or day 28
Number of Participants With Delirium
Time frame: From randomization until extubation or day 28
Mortality
Time frame: From randomization to day 60
Number of Participants With Psychological disorders
Time frame: at 90 days of hospital discharge
Number of Participants With Cognitive Disorders
Time frame: at 90 days of hospital discharge
Number of Participants With Treatment-Related Adverse Events
Time frame: From randomization to day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
José M. Añón, MD, PhD principal investigator
Hospital Universitario La Paz. IdiPAZ
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Isoflurane and Propofol in people with Sedation and Airway Extubation, run by Instituto de Investigación Hospital Universitario La Paz at 22 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact José M. Añón, MD, PhD (+(34) 912071307, jmaelizalde@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator-free days at day 28 from randomization (time frame: From randomization until day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.