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

Phase 3

Active, not recruiting

• Conditions: Post-Intensive Care Syndrome; Sedation
• Interventions: Drug: Inhaled isoflurane administered by Sedaconda ACD-S; Drug: Intravenous infusion of propofol

• Registration Number: NCT06809218
• Lead Sponsor: Sedana Medical

Brief Summary

This pooled analysis will assess Cognitive, Mental Health, Functioning, and Quality of Life Assessments data from the Phase 3 registration studies INSPiRE-ICU 1 (NCT05312385) and INSPiRE-ICU 2 (NCT05327296) to explore potential differences in Long-Term Outcomes at 3 and 6 months after treatment between critically ill mechanically ventilated patients sedated with inhaled isoflurane compared to sedated with intravenous propofol.

The analyses were pre-planned and agreed prior to completion of enrollment of either study.

Detailed Description

SED003 and SED004 are two Phase 3 studies conducted in the US, with a goal to demonstrate non-inferiority of isoflurane administered via Sedaconda ACD-S to the current standard of care (SOC), IV propofol infusion, in patients requiring sedation and mechanical ventilation in the ICU.

These studies are therapeutic confirmatory (Phase 3), multicenter, randomized, controlled, open-label, assessor-blinded studies. Approximately 470 patients receiving mechanical ventilation and requiring continuous sedation at approximately 30 sites in total in the United States (US) will be randomized in a 1.5:1 ratio to inhaled isoflurane (administered via the Sedaconda ACD-S device) or propofol (administered via IV infusion) for sedation, respectively. In addition, approximately 3 to 5 run-in training patients per site will be enrolled. The treatment duration is expected to be at least 12 hours and may last up to 48 (±6) hours or to the time for extubation, whichever occurs first, with a follow up period of 6 months.

Patients eligible for the studies will either have planned surgery with anticipated need for sedation and mechanical ventilation in the ICU (ie, postoperative patients) for \>12 hours or have already been admitted to the ICU and anticipate needing sedation and mechanical ventilation for \>12 hours.

For further information about the studies, refer to INSPiRE-ICU 1 (NCT05312385) and INSPiRE-ICU 2 (NCT05327296).

In drug studies of critically ill patients, outcomes may be assessed at remote timepoints and not merely in the ICU. This is because the "success" of interventions is not defined merely by their impact in the hospital but also by their persistent effects. The CIBS Center at Vanderbilt University Medical Center will conduct the long-term outcome assessments for a subset of patients in the INSPiRE-ICU studies.

A comprehensive battery that combines tests from diverse and relevant domains of functioning and balances the need to be sufficiently challenging to patients as well as the need to be feasibly administered and well tolerated. Crucially, this battery can be given by telephone, which allows for it to be administered by the CIBS Center to individuals from around the country, regardless of which enrollment sites they are from.

A significant proportion of the enrolled patients in the two studies will not have any follow-up data due to expected mortality as well as loss to follow-up. Since the two studies (INSPiRE-ICU 1 \& 2) are identical in design and long-term follow-up is standardized and centralized, pooling of the long-term outcomes allows for improved precision of analyses.

Study Timeline

• Study Start: 2022-04-22
• Primary Completion: 2024-11-14
• Status Verified: 2025-01
• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-29
• Last Update Submitted: 2025-01-29
• Study Completion: 2025-01-30
• Study First Posted: 2025-02-05
• Last Update Posted: 2025-02-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 312

Inclusion Criteria

1. Patients who are enrolled in INSPiRE-ICU1 (NCT05312385) or INSPiRE-ICU2 (NCT05327296) and survived to discharge.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhaled isoflurane administered via Sedaconda ACD-S	Inhaled isoflurane administered by Sedaconda ACD-S	Intervention: isoflurane
Propofol administered as intravenous infusion	Intravenous infusion of propofol	Treatment: propofol

Primary Outcome Measures

Name	Time	Method
To compare cognitive function 3 months post randomization in isoflurane- vs propofol-treated patients	3 months post Randomization	A patient is classified as cognitive impaired if the patient has a score 2 SD (or more) worse than population mean for one test or has a score 1.5 SD (or more) worse than population mean in two or more of the following tests: TICS, WAIS IV Digit Span, Hayling Sentence Completion Test, Controlled Oral Word Association, WMS IV - Immediate Memory (Adult/Older Adult) and WMS IV - Delayed Memory (Adult/Older Adult), at 3 months post randomization.; The analysis will take into account age, sex, level of education, total IQCODE score at baseline, total SAPS total score at baseline, medical or surgical admission duration of mechanical ventilation before randomization, study drug and treatment duration as factors.

Secondary Outcome Measures

Name	Time	Method
To compare memory panorama from time in the ICU in isoflurane- vs propofol-treated patients	3 months post Randomization	Number of factual memories, memories of feelings, or delusional memories, as assessed by the ICU Memory Tool, collected at 3 months follow-up
To compare physical outcomes and trajectories at 3 and 6 months post randomization in isoflurane- vs propofol-treated patients	3 and 6 months post Randomization	Activities of daily living, as assessed by the Katz ADL, at 3 and 6 months post randomization. Score ranges between 0 and 6, where 0 is the worst outcome.
To compare depressive symptoms at 3 months post randomization in isoflurane- vs propofol-treated patients	3 months post Randomization	Depression, as assessed by PROMIS Depression questionnaire, at 3 months post randomization
To compare anxiety symptoms at 3 months post randomization in isoflurane- vs propofol-treated patients	3 months post Randomization	Anxiety symptoms, as assessed by PROMIS Anxiety questionnaire, at 3 months post randomization
To compare post-traumatic stress symptoms at 3 months post randomization in isoflurane- vs propofol-treated patients	3 months post Randomization	Post-traumatic stress symptoms, as assessed by IES-R, at 3 months post randomization
To compare quality of life at 3 months post randomization in isoflurane- vs propofol-treated patients	3 months post Randomization	Quality of life at 3 months post-randomization, as assessed by WHODAS 2.0

Trial Locations

Locations (1)

The Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center; 🇺🇸 Nashville, Tennessee, United States