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.
