Sedana Medical (SEDANA) Study Result summary

SESAR study overview and results

• SESAR was a multicenter, randomized controlled trial in France comparing inhaled sevoflurane to propofol for sedation in moderate to severe ARDS patients, with Sedana Medical providing limited support and not involved in study conduct.

• 700 patients were randomized (687 enrolled) in 37 French ICUs; the primary endpoint was ventilator-free days at 28 days.

• Propofol group had 2.1 more ventilator-free days than sevoflurane, and the primary endpoint was lower in the sevoflurane group (hazard ratio 0.76, 95% CI 0.5–0.97).

• Higher mortality was observed in the sevoflurane group (52.9% at 90 days vs. 44.3% for propofol), with early separation of mortality curves.

• Excess deaths in the sevoflurane group were mainly due to refractory shock and multi-organ failure.

Interpretation and possible causes

• Key factors discussed include the impact of COVID-19, likely high doses of sevoflurane, and sevoflurane-related renal failure.

• COVID-19 disrupted training and monitoring, leading to less proficiency with inhaled sedation and removal of mandatory sedation depth monitoring.

• Indicators suggest patients in the sevoflurane group were over-sedated, with higher norepinephrine use and deeper sedation levels.

• Sevoflurane was associated with renal dysfunction, polyuria, and hyponatremia, increasing vulnerability to sedatives and contributing to multi-organ failure.

• Authors concluded findings do not support sevoflurane for sedation in critically ill ARDS patients.

Product differentiation and company perspective

• Sevoflurane (SESAR study drug) differs in metabolism and toxicity from Sedaconda (isoflurane), the only approved ICU sedative.

• Sedaconda (isoflurane) studies showed non-inferiority to propofol, reduced opioid use, shorter wake-up times, and no renal harm in adults and children.

• U.S. INSPiRE-ICU trials confirmed isoflurane’s non-inferiority for sedation and similar or lower rates of serious adverse events compared to propofol.

• Posthoc analysis found 3.5 more ICU-free days and less additional sedative use with isoflurane versus propofol.

• Extensive safety data for isoflurane in anesthesia and ICU sedation, including ARDS patients, supports its use.