Comparison of the Efficacy of HSK3486 and Propofol for Induction of General Anesthesia in Adults: A Multicenter, Randomized, Double-Blind, Controlled, Phase 3 Noninferiority Trial
Tong J. Gan, Todd Bertoch, Ashraf S. Habib, Pangke Yan, Rong Zhou, Yu-Ling Lai, Xiao Liu, Michael Essandoh, William L. Daley, Adrian W. Gelb- Anesthesiology and Pain Medicine
Background
Propofol is an intravenous anesthetic associated with hypotension, respiratory depression, and injection-site pain. HSK3486 injectable emulsion (ciprofol) is a 2,6-disubstituted phenol derivative with fast onset and quick, stable recovery. Prior studies support HSK3486 as an effective, safe anesthetic with substantially less injection-site pain than propofol. This study’s primary objective was to investigate the noninferiority of HSK3486 compared with propofol in successful general anesthesia induction.
Methods
Two hundred fifty-five participants were enrolled in HSK3486-304, a multicenter, randomized (2:1), double-blind, propofol-controlled, phase 3 study evaluating HSK3486 for general anesthesia induction in adults undergoing elective surgery with endotracheal intubation. The primary endpoint was successful anesthesia induction, defined as ≤1 on the Modified Observer’s Assessment of Alertness/Sedation scale. Key secondary endpoints were proportion of participants with injection-site pain on the Numerical Rating Scale ≥1 and a composite endpoint, including the proportion of participants successfully induced while maintaining the desired anesthetic depth and without substantial cardiac and respiratory events. Safety endpoints included adverse events, abnormal vital signs, and injection-site pain.
Results
Two hundred fifty-one participants (HSK3486, n=168; propofol, n=83) were included in the analyses. General anesthesia was successfully induced in 97.0% vs 97.6% of participants with HSK3486 and propofol, respectively. The difference in success rate was −0.57% (95% CI: −5.4%, 4.2%); the noninferiority boundary of −8% was not crossed. Thirty participants (18.0%) had injection-site pain with HSK3486 vs 64 (77.1%) with propofol (p<.0001). Eighty-one participants (48.2%) with HSK3486 vs 42 (50.6%) with propofol (p=.8780) satisfied the composite endpoint. When injection-site pain was excluded the incidence of treatment-emergent adverse events related to study drug was 17.9% for HSK3486 and 14.5% for propofol.
Conclusions
The study met its primary objective and endpoint, demonstrating noninferiority of HSK3486 compared with propofol in successful anesthetic induction. Substantially less injection-site pain was associated with HSK3486 than with propofol.