Sedana Medical (SEDANA) Study Result summary

SESAR study overview and context

• SESAR was a multicenter, randomized controlled trial in France evaluating inhaled sevoflurane versus intravenous propofol for sedation in moderate to severe ARDS patients, enrolling 687–700 patients across 37 ICUs, with Sedana Medical providing limited support and materials.

• Patients were randomized to deep sedation with either sevoflurane via Sedaconda ACD or propofol for up to 7 days.

• The study was led by Prof. Matthieu Jabaudon and published in JAMA.

• The study was conducted during COVID-19, impacting training, protocol adherence, and monitoring of sedation depth.

• Removal of mandatory sedation monitoring and limited training likely contributed to dosing challenges and over-sedation.

Key SESAR study results

• Propofol group had 2.1 more ventilator-free days than sevoflurane, with the primary endpoint showing lower ventilator-free days for sevoflurane (median 0.0 days vs. 0.0 days; IQRs differed; 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.

• Seven-day mortality was also higher for sevoflurane (19.4%) compared to propofol (13.5%).

• Main causes of death included multi-organ failure and refractory shock, with refractory shock notably higher in the sevoflurane group.

• Over-sedation and renal dysfunction were identified as likely contributors to excess mortality in the sevoflurane group.

Interpretation and implications of SESAR findings

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

• COVID-19 disruptions led to less effective training and protocol deviations, likely resulting in higher sevoflurane dosing.

• Sevoflurane-related renal dysfunction, including nephrogenic diabetes insipidus and acute kidney injury, was more frequent and is dose/duration dependent.

• The SESAR results do not generalize to isoflurane, which has demonstrated safety and efficacy in multiple trials.

• The company is intensifying efforts to convert off-label sevoflurane users to isoflurane, especially in markets like France.