Drug design, development and therapy
Adjunctive Oliceridine During Propofol or Ciprofol Sedation for Same-Session Bidirectional Endoscopy in Older Adults: A Multicenter Randomized 2×2 Factorial Trial
By Ji Y, Xu C, Yang S and 9 others.
Abstract
Purpose
We evaluated adjunctive oliceridine with propofol or ciprofol in older adults undergoing same-session bidirectional endoscopy. Patients and methods: In this multicenter, double-blind, placebo-controlled 2×2 factorial trial, 360 adults aged 65-80 years were randomized 1:1:1:1 to oliceridine or saline placebo with propofol or ciprofol. The primary outcome was time from completion of the initial sedative dose to the first Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of 5, confirmed by two subsequent scores of 5 at 1-min intervals. Main-effect comparisons were prespecified; interaction and simple-effect analyses were exploratory because the trial was not powered for interaction testing.
Results
The primary analysis included 357 participants. Estimated marginal mean differences in awakening time were -1.42 min for oliceridine versus placebo (95% CI -2.43 to -0.40, P = 0.007) and -1.84 min for propofol versus ciprofol (95% CI -2.85 to -0.82, P < 0.001); the latter was smaller than the prespecified 3-min clinically important difference. In the post hoc final-dose analysis, the oliceridine-placebo difference was 0.09 min (95% CI -0.78 to 0.96, P = 0.833). Exploratory interaction analysis suggested a greater oliceridine effect with ciprofol. Oliceridine reduced supplemental sedative use (risk difference -16.7%, 95% CI -24.8% to -8.5%, adjusted P < 0.001) and shortened time to discharge readiness (difference -1.64 min, 95% CI -2.30 to -0.99, adjusted P < 0.001), but increased hypotension (risk difference 15.6%, 95% CI 7.6% to 23.6%, P < 0.001).