Inhaled Isoflurane vs. IV Propofol for ICU Sedation

(INSPiRE-ICU1 Trial)

Not currently recruiting at 13 trial locations

Overseen By Magnus Falkenhav, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sedana Medical

Must not be taking: Benzodiazepines, Barbiturates

Disqualifiers: Neurological condition, Hemodynamic compromise, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 48 (±6) hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two sedation methods for ICU patients requiring a ventilator and continuous sedation. It tests inhaled isoflurane, delivered through a special device, against intravenous propofol to determine which is safer and more effective. Suitable candidates for this trial are those on a ventilator needing sedation for over 12 hours in the ICU. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the development of safer and more effective sedation methods.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you require IV benzodiazepines or barbiturates for seizures or dependencies, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that inhaled isoflurane might be safer for ICU patients. Studies have found that it can help patients wake up faster and leave the ICU sooner compared to drugs given through an IV. Earlier research suggests that patients using isoflurane had a 5% lower chance of dying within 30 days compared to those using other sedatives.

For propofol, the safety information is mixed. Some studies highlight its benefits, such as a lower risk of death and quicker ICU discharges. However, propofol also carries risks, including heart problems and a rare but serious condition called propofol infusion syndrome (PRIS), which can be severe.

In summary, both treatments have been used safely in many cases, but each also has specific risks. These factors are important to consider when thinking about joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Isoflurane and Propofol offer different approaches to ICU sedation. Unlike the standard intravenous sedation with Propofol, Isoflurane is inhaled using a device called the Sedaconda ACD-S. This inhalation method could provide more precise control over sedation levels and potentially faster recovery times for patients. Additionally, Isoflurane's distinct method of administration might reduce some of the side effects associated with IV sedation, making it a promising alternative for patient care in intensive care units.

What evidence suggests that this trial's treatments could be effective for ICU sedation?

This trial will compare inhaled isoflurane with intravenous propofol for sedation in ICU patients. Research has shown that inhaled isoflurane may offer advantages over intravenous propofol. Studies have found that patients using inhaled isoflurane tend to wake up faster and can be taken off a ventilator sooner. Specifically, one study discovered that the 30-day death rate was 5% lower for patients using isoflurane compared to those using propofol. This suggests that isoflurane might lead to better outcomes for some patients in critical care. ^{6 7 8 9 10}

Who Is on the Research Team?

Kimberly Rengel, M.D.

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

Adults over 18 who need mechanical ventilation and sedation for more than 12 hours in the ICU can join. They must require a specific level of sedation (RASS <0). Excluded are those with severe neurological issues, life-threatening conditions, allergies to isoflurane or propofol, certain heart problems, pregnant or breastfeeding women, and patients on other conflicting studies.

Inclusion Criteria

I am expected to need a breathing machine and sedation in the ICU for more than 12 hours.

I am on constant sedation due to my medical condition.

I am on constant sedation due to my medical condition.

Exclusion Criteria

Ventilator tidal volume <200 or >1000 mL at Baseline

I am allergic or cannot take propofol or isoflurane.

I am receiving care focused on comfort, not curing my illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either inhaled isoflurane via Sedaconda ACD-S or intravenous propofol for sedation while mechanically ventilated in the ICU

Up to 48 (±6) hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including mortality and cognitive recovery assessments

6 months

Long-term follow-up

Participants' mortality and other outcomes are assessed at 3 and 6 months post-randomization

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Isoflurane
• Propofol

Trial Overview The trial compares two types of sedatives: inhaled isoflurane using Sedaconda ACD-S versus intravenous propofol. It aims to determine which one is safer and more effective for keeping ICU patients under sedation while they're on a ventilator.

How Is the Trial Designed?

Group I: Isoflurane Experimental Treatment 1 Intervention

Inhaled isoflurane administered via Sedaconda ACD-S

Group II: Propofol Active Control 1 Intervention

Propofol administered as intravenous infusion

Who Is Running the Clinical Trial?

Sedana Medical

Lead Sponsor

Trials

5

Recruited

900+

Published Research Related to This Trial

Inhaled sedation using agents like isoflurane and sevoflurane is now possible in ICU settings, offering a well-tolerated and adjustable sedation option for patients, provided that proper equipment and training are available.

These inhaled agents not only serve as effective sedatives but may also offer additional clinical benefits for ICU patients, suggesting a promising alternative to traditional intravenous sedation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled sedation in the intensive care unit. Jabaudon, M., Zhai, R., Blondonnet, R., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39972505/

Safety and effectiveness of inhaled sedation in critically ill ... Main results: Fifteen trials with a total of 1185 patients were included, including 568 in the inhaled sedation group and 617 in the intravenous ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11837438/

Safety and effectiveness of inhaled sedation in critically ill ... Inhaled sedation has advantages over intravenous sedation in terms of awakening time, extubation time, and ICU LOS (non-cardiac ICU).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06809218

A Pooled Analysis of Long-Term Outcomes After Inhaled ... A Pooled Analysis of Long-Term Outcomes After Inhaled Isoflurane Via the Sedaconda ACD-S Compared to Intravenous Propofol. ClinicalTrials.gov ID NCT06809218.

4. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-025-05603-4

Volatile sedation in critically ills adults undergoing mechanical ... propofol for ICU sedation and found that 30-day mortality was 5% lower in the isoflurane group (unpublished data available on clinicaltrials.gov ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05312385

NCT05312385 | Efficacy and Safety of Inhaled Isoflurane ... This is a study to compare safety and efficacy of inhaled isoflurane administered via the Sedaconda ACD-S device system versus intravenous propofol for sedation ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10349530/

Propofol in ICU Settings: Understanding and Managing Anti ... This review concisely summarizes the dual arrhythmic cardiovascular effects of propofol and a rare but serious complication, propofol infusion syndrome (PRIS).

7. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-023-04431-8

an updated meta-analysis of randomized clinical trials A statistically significant mortality increase in the propofol group was confirmed in subgroups of cardiac surgery, adult patients, volatile ...

8. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.201312-2291OC

American Journal of Respiratory and Critical Care Medicine Patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024922

Dexmedetomidine or Propofol for Sedation in Mechanically ... Trials comparing dexmedetomidine with benzodiazepines in adults have shown that the use of dexmedetomidine results in improvement in outcomes ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883944121000629

A systematic review and meta-analysis of propofol versus ... Sedation with propofol compared to midazolam is associated with improved clinical outcomes in ICU, with reduced ICU stay MV time and extubation time.