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. Previous studies support HSK3486 as an effective, safe anesthetic with substantially less injection-site pain than propofol. The primary objective of this study 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 tracheal intubation. The primary endpoint was successful anesthesia induction, defined as 1 or less 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 of 1 or greater 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% versus 97.6% of participants with HSK3486 and propofol, respectively. The difference in success rate was −0.57% (95% CI, −5.4 to 4.2%); the noninferiority boundary of −8% was not crossed. Thirty participants (18.0%) had injection-site pain with HSK3486 versus 64 (77.1%) with propofol (P < 0.0001). Eighty-one participants (48.2%) with HSK3486 versus 42 (50.6%) with propofol (P = 0.8780) 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.

Editor’s Perspective
What We Already Know about This Topic
  • HSK3486 (ciprofol) is a propofol analog that has been reported to be an effective hypnotic, with a safety profile similar to that of propofol but with less injection-site pain and fewer respiratory-related adverse events
What This Article Tells Us That Is New
  • The noninferiority of HSK3486 compared with propofol for successful induction of general anesthesia (Modified Observer’s Assessment of Alertness/Sedation Score of 1 or less) was assessed in a randomized, double-blind, controlled, phase 3 clinical trial of 251 adults undergoing elective surgery
  • Induction success rate was 97.0% for patients administered HSK3486 and 97.6% for those administered propofol; because the lower bound of the 95% CI for the difference in success rate did not cross the noninferiority boundary of –8%, HSK3486 was deemed noninferior to propofol for successful induction of anesthesia
  • The incidence of injection-site pain was 18.0% in patients who received HSK3486 and 77.1% in those who received propofol
  • The incidence of treatment-emergent adverse events related to study drug was 17.9% for patients administered HSK3486 and 14.5% for those administered propofol when injection-site pain was excluded