A two-phase randomized study of oliceridine versus sufentanil for gastrointestinal endoscopy

Oliceridine is a novel G protein-biased μ-opioid receptor (MOR) agonist. It provides analgesic effects and reduces opioid-related adverse events (ORAEs). It has shown good efficacy in acute pain management. However, compared with traditional opioids, its optimal dosage and safety in gastrointestinal endoscopy have not been clearly established. We aimed to determine the 95% effective dose (ED₉₅) of oliceridine and sufentanil in gastrointestinal endoscopy and simultaneously evaluate their therapeutic effects.

This two-phase study was designed to evaluate the clinical effective dose and clinical safety of oliceridine. In the first phase, we used the modified Dixon's up-and-down method to determine the ED₅₀ and ED₉₅ of oliceridine and sufentanil during sedated gastrointestinal endoscopy. In Phase 2, 160 patients undergoing gastrointestinal endoscopy were randomized to receive oliceridine or sufentanil at the predefined doses in combination with propofol titrated to a standardized depth of sedation. The primary outcomes were time to discharge and incidence of respiratory depression. Secondary outcomes included recovery profiles and adverse events.

In the first phase, we determined the ED₉₅ to be 14.52 μg/kg (95% CI: 12.44-24.23) for oliceridine and 0.048 μg/kg (95% CI: 0.044-0.071) for sufentanil. In the second phase, the oliceridine group achieved a significantly shorter discharge time (13.0 min vs. 15.0 min, P = 0.044) and reached the recovery criterion (modified Aldrete score ≥9) more quickly (5.0 min vs. 6.0 min, P = 0.013). Importantly, the incidence of respiratory depression was markedly lower in the oliceridine group (7.5% vs. 20%, P = 0.039). Other adverse events were similar between groups.

At doses derived from a sequential dose-finding design, oliceridine combined with propofol was associated with a lower observed incidence of respiratory depression and modestly faster recovery compared with sufentanil during gastrointestinal endoscopy in low-risk patients. Given the methodological limitations of dose estimation and the limited power for safety outcomes, these findings should be interpreted cautiously and warrant confirmation in larger studies.

Identifier ChiCTR2500095827.