Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial. A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests. In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750). Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.

Ciprofol is a propofol analogue with improved pharmacokinetic properties. A multi‐centre, non‐inferiority trial was conducted to compare the deep sedation properties of ciprofol and propofol with a non‐inferiority margin of 8% in patients undergoing gastroscopy and colonoscopy. In total, 289 patients were randomly allocated for surgery (259 colonoscopy and 30 gastroscopy) at a 1:1 ratio to be given intravenous injections of ciprofol (0.4 mg/kg) or propofol (1.5 mg/kg). The primary outcome was the success rate of colonoscopy defined as colonoscopy completion with no need for an alternative sedative or >5 ciprofol or propofol top up doses within any 15‐min time period. The success rate of colonoscopy was 100% in the ciprofol group vs. 99.2% in the propofol group (mean difference 0.8%, 95% CI: −2.2% to 4.2%). Except for the gastrointestinal lesions found during the gastroscopy and colonoscopy procedures, the occurrence rates of adverse drug reactions in the ciprofol and propofol groups were 31.3% and 62.8%, respectively (P < 0.001). Pain on injection was less common in the ciprofol group (4.9% vs. 52.4%, P < 0.001). The outcomes demonstrated that ciprofol was non‐inferior to propofol with regard to successful sedation for gastroscopy or colonoscopy procedures and no obvious important adverse events occurred.

BACKGROUND: HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABA_A) receptor. OBJECTIVE: To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN: A single-blinded, randomised, parallel-group, phase 3 trial. SETTING: Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS: A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonneurosurgical elective surgery. INTERVENTION: Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg⁻¹) or propofol (2.0 mg kg⁻¹) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg⁻¹ h⁻¹, and were adjusted to maintain a bispectral index (BIS) of 40–60 until the end of surgery. MAIN OUTCOME MEASURES: Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >−8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS: Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI −4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P = 0.451) in the HSK3486 and propofol groups. CONCLUSION: HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04511728.

Background Fiberoptic bronchoscopy is a complex procedure with the need for sufficient patient anesthesia/sedation while maintaining safety. This trial aimed to evaluate the efficacy, safety, and pharmacokinetics of HSK3486 during fiberoptic bronchoscopy. Methods This multicenter, double-blind, randomized, non-inferiority, parallel-group phase 3 trial was conducted in patients who underwent fiberoptic bronchoscopy. Patients randomly received HSK3486 0.4 mg/kg (N = 134) or propofol 2.0 mg/kg (N = 133). The primary efficacy endpoint was the successful rate of fiberoptic bronchoscopy, and secondary efficacy endpoints included successful induction of anesthesia/sedation, duration, time to being fully alert, and time to patient discharge. Safety assessments and drug concentrations were also measured. Results A total of 267 patients completed fiberoptic bronchoscopy, with a success rate of 100% and a 95% confidence interval of − 2.8 to 2.8% for the difference between the groups, which met the predesigned criteria of > − 8%, confirming the non-inferiority of anesthesia/sedation produced by HSK3486 compared to propofol. Among the secondary efficacy endpoints, only time to full alertness (median 8.50 vs. 6.00 min, P = 0.012) and time to discharge (median 13.00 vs. 9.87 min, P = 0.002) were slightly longer in the HSK3486 group. The incidence of adverse events was significant lower in the HSK3486 group (52.6 vs. 76.5%, P < 0.001) mainly because of less pain on injection (4.4 vs. 39.4%, P < 0.001) compared to the propofol group. HSK3486 had a similar terminal elimination half-life as propofol. Conclusions HSK3486 exhibited non-inferiority anesthesia/sedation compared to propofol in patients undergoing fiberoptic bronchoscopy, and had a good safety profile with a lower incidence of pain on injection. Trial Registration Clinicaltrials.gov, NCT04111159, registered on 1 October 2019

Nalbuphine is as effective as morphine as a perioperative analgesic but has not been compared directly with sufentanil in clinical trials. The aims of this study were to compare the efficacy and safety of nalbuphine with that of sufentanil in patients undergoing colonoscopy and to determine the optimal doses of nalbuphine in this indication. Two hundred and forty consecutive eligible patients aged 18–65 years with an American Society of Anesthesiologists classification of I–II and scheduled for colonoscopy were randomly allocated to receive sufentanil 0.1 μg/kg (group S), nalbuphine 0.1 mg/kg (group N1), nalbuphine 0.15 mg/kg (group N2), or nalbuphine 0.2 mg/kg (group N3). Baseline vital signs were recorded before the procedure. The four groups were monitored for propofol sedation using the bispectral index, and pain relief was assessed using the Visual Analog Scale and the modified Behavioral Pain Scale for non-intubated patients. The incidences of respiratory depression during endoscopy, nausea, vomiting, drowsiness, and abdominal distention were recorded in the post anesthesia care unit and in the first and second 24-hour periods after colonoscopy. There was no significant difference in analgesia between the sufentanil group and the nalbuphine groups (p>0.05). Respiratory depression was significantly more common in group S than in groups N1 and N2 (p<0.05). The incidence of nausea was significantly higher in the nalbuphine groups than in the sufentanil group in the first 24 hours after colonoscopy (p<0.05). Nalbuphine can be considered as a reasonable alternative to sufentanil in patients undergoing colonoscopy. Doses in the range of 0.1–0.2 mg/kg are recommended. The decreased risks of respiratory depression and apnea make nalbuphine suitable for patients with respiratory problems.