Efficacy and safety of sedation induced with cipepofol alone versus a dexmedetomidine plus propofol regimen for patients requiring mechanical ventilation: a randomized, open-label, non-inferiority trial

Abstract

Objective This randomized, open-label, non-inferiority trial aimed to compare the safety and efficacy of cipepofol vs. a dexmedetomidine plus propofol regimen for sedating intensive care unit (ICU) patients requiring mechanical ventilation (MV). Methods This single-center study randomly assigned Chinese adult patients to cipepofol or dexmedetomidine/propofol groups (1:1 ratio). Cipepofol was infused intravenously at a loading dose of 0.1 mg/kg (over 4 min ± 30 s) and an initial maintenance dose of 0.3 mg/kg/h, which was adjusted within the range 0.06–0.8 mg/kg/h to produce sedation in the range of 0 to −4 on the Richmond Agitation-Sedation Scale. Propofol and dexmedetomidine were infused intravenously at initial dosages of 0.3 mg/kg/h and 0.2 μg/kg/h, respectively (neither drug required a loading dose). When the maximum dexmedetomidine dose (0.7 μg/kg/h) was insufficient to achieve the target sedation depth or intolerance developed, the propofol dose was modified within the range 0.3–4.0 mg/kg/h. The primary endpoint was sedation success rate, and the non-inferiority margin was set as 10%. Results Of 72 patients enrolled for the intention-to-treat (ITT) analysis, 71 patients were included in the full analysis set/per-protocol set (FAS/PPS). The sedation success rates for the cipepofol and dexmedetomidine/propofol groups were 100% and 97.2%, respectively, in the ITT analysis and 100% for both in the FAS/PPS. Non-inferiority was established, and the lower limit of the 95% confidence interval (CI) for the inter-group difference was −1.34% for the ITT analysis and −9.64% for the FAS/PPS. There were no differences between groups in sedation compliance rate, extubation and recovery times, MV duration, or length of ICU stay (all P > 0.05). Cipepofol was associated with lower incidences of treatment-emergent adverse events (TEAEs; 33.3% vs. 66.7%) and drug-related TEAEs (30.6% vs. 63.9%) than dexmedetomidine/propofol (all P < 0.05). Notably, hypotension incidence was lower in the cipepofol group than in the dexmedetomidine/propofol group (30.6% vs. 61.1%, P = 0.017). Conclusion Cipepofol was not inferior to dexmedetomidine/propofol for >24-h sedation in Chinese adult patients receiving MV in the ICU. Furthermore, cipepofol elicited fewer hypotensive events than dexmedetomidine/propofol. Large-scale, multicenter studies are warranted to confirm our findings.