Patients undergoing surgeries and procedures often receive anesthetic agents for sedation. Ciprofol, a novel anesthetic agent, was developed independently in China by the Haisco Pharmaceutical Group in 2017. It received approval from the China National Medical Products Administration (NMPA) for sedation during gastrointestinal endoscopy on December 15, 2020, following a priority review. Subsequently, ciprofol was also approved for sedation during bronchoscopy, as well as for the induction and maintenance of general anesthesia. Recently, the NMPA approved a new indication for ciprofol for sedation during intensive care, indicating its expanding clinical uses. This article examines the clinical trials that have assessed the various clinical uses of ciprofol.

Ciprofol has a chemical structure of (R)-2-(1-cyclopropyl ethyl)-6-isopropylphenol, bearing a strong resemblance to propofol, a commonly used anesthetic agent. The inclusion of a cyclopropyl group in ciprofol’s side chain increases its lipophilicity compared to propofol, leading to a higher affinity for GABA receptors. Ciprofol is administered intravenously and is quickly removed from the bloodstream. Its concentration-time profile mirrors that of propofol.

Several clinical trials have evaluated the effectiveness and safety of ciprofol in comparison to propofol. One such study, a phase III clinical trial conducted in China, examined the impact of ciprofol and propofol on achieving deep sedation during gastroscopy (n=30) and colonoscopy (n=259) procedures. According to Li et al., the success rate for colonoscopy was 100% in the ciprofol group and 99.2% in the propofol group. Both groups achieved a 100% success rate for gastroscopy. There were no significant differences observed between the two groups regarding induction time, insertion time, and insertion success rates.

Luo et al. conducted a phase III trial involving patients who underwent fiber-optic bronchoscopy (n=267) to assess the effectiveness, safety, and pharmacokinetics of ciprofol. Both the ciprofol and propofol groups achieved a 100% success rate in completing the procedure. Additionally, the satisfaction scores for anesthesia/sedation reported by patients and anesthesiologists in the ciprofol group were similar to those in the propofol group. However, patients in the ciprofol group took slightly longer to fully regain alertness and to be discharged compared to the propofol group. This multicenter, double-blind, randomized, noninferiority, parallel-group trial demonstrated that ciprofol produces anesthetic/sedative effects comparable to propofol in patients undergoing bronchoscopy, with a lower incidence of pain upon injection.

In a phase III trial by Wang et al., ciprofol was compared to propofol for effectively inducing general anesthesia in patients (n=176) undergoing elective surgery. The study found a 100.0% success rate for anesthesia induction in both groups, demonstrating that ciprofol was not inferior to propofol in this regard. These findings suggest that ciprofol is a promising option for patients scheduled for elective surgery.

Another study by Liu et al. aimed to assess the safety and efficacy of ciprofol for sedation in mechanically ventilated patients. The median sedation durations for ciprofol and propofol were 60.0 minutes. Both groups showed similar incidences of drug-related and sedation-related treatment-emergent adverse events, such as hypotension and sinus bradycardia. The study concluded that ciprofol was comparable to propofol in terms of efficacy and tolerance in ICU patients on mechanical ventilation. According to information from Clinicaltrials.gov, a phase III clinical trial evaluating the efficacy and safety of ciprofol injection for inducing sedation/anesthesia in subjects undergoing gynecological outpatient surgeries has been completed in China, with the indication currently under review and approval.

Overall, ciprofol, a novel anesthetic compound, has found clinical uses in colonoscopy, bronchoscopy, elective surgery, and ICU settings. As more data is collected and reviewed, the clinical uses of ciprofol are likely to expand.

References

Li J, Wang X, Liu J, Wang X, Li X, Wang Y, Ouyang W, Li J, Yao S, Zhu Z, Guo Q, Yu Y, Meng J, Zuo Y. Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi-centre, non-inferiority, randomized, controlled phase 3 clinical trial. Basic Clin Pharmacol Toxicol. 2022 Aug;131(2):138-148. doi: 10.1111/bcpt.13761. Epub 2022 Jun 10. PMID: 35653554; PMCID: PMC9543620.

Luo Z, Tu H, Zhang X, Wang X, Ouyang W, Wei X, Zou X, Zhu Z, Li Y, Shangguan W, Wu H, Wang Y, Guo Q. Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study. CNS Drugs. 2022 Mar;36(3):301-313. doi: 10.1007/s40263-021-00890-1. Epub 2022 Feb 14. PMID: 35157236; PMCID: PMC8927014.

Wang X, Wang X, Liu J, Zuo YX, Zhu QM, Wei XC, Zou XH, Luo AL, Zhang FX, Li YL, Zheng H, Li H, Wang S, Wang DX, Guo QL, Liu CM, Wang YT, Zhu ZQ, Wang GY, Ai YQ, Xu MJ. Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study. Eur Rev Med Pharmacol Sci. 2022 Mar;26(5):1607-1617. doi: 10.26355/eurrev_202203_28228. PMID: 35302207.

Liu Y, Yu X, Zhu D, Zeng J, Lin Q, Zang B, Chen C, Liu N, Liu X, Gao W, Guan X. Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial. Chin Med J (Engl). 2022 May 5;135(9):1043-1051. doi: 10.1097/CM9.0000000000001912. PMID: 34924506; PMCID: PMC9276409.

Lu M, Liu J, Wu X, Zhang Z. Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia? Biomed Res Int. 2023 Jan 19;2023:7443226. doi: 10.1155/2023/7443226. PMID: 36714027; PMCID: PMC9879693.