Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Mar;36(3):301-313.
doi: 10.1007/s40263-021-00890-1. Epub 2022 Feb 14.

Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study

Zhen Luo #  1 , Hong Tu #  1 , Xiang Zhang  1 , Xiao Wang  2 , Wen Ouyang  3 , Xinchuan Wei  4 , Xiaohua Zou  5 , Zhaoqiong Zhu  6 , Yalan Li  7 , Wangning Shangguan  8 , Hui Wu  9 , Yaping Wang  10 , Qulian Guo  11
Affiliations
Clinical Trial

Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study

Zhen Luo et al. CNS Drugs. 2022 Mar.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

ZL, HT, XZ, XW, WOY, XCW, XHZ, ZQZ, YLL, WNSG, HW, YPW and QLG declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Enrolment flow diagram. FAS full analysis set, PKS pharmacokinetics analysis set, SS safety set
Fig. 2
Fig. 2
The time course of median Modified Observer Assessment of Alertness/Sedation (MOAA/S) score in the two groups
Fig. 3
Fig. 3
Vital signs over time. A Systolic blood pressure (SBP), B diastolic blood pressure (DBP), C mean arterial pressure (MAP), D heart rate, E respiratory rate and F oxygen saturation (SpO2)
Fig. 4
Fig. 4
Mean plasma concentration-time curve linear plot. The plasma concentration during the first 6 h followed first-order kinetics
See this image and copyright information in PMC

References

    1. Alon D, Pertzov B, Gershman E, Frishman M, Rahman NA, Rosengarten D, et al. The safety of laryngeal mask airway-assisted bronchoscopy versus standard nasal bronchoscopy. Respiration. 2017;93(4):279–284. doi: 10.1159/000456551. - DOI - PubMed
    1. Wahidi MM, Jain P, Jantz M, Lee P, Mackensen GB, Barbour SY, et al. American College of Chest Physicians consensus statement on the use of topical anesthesia, analgesia, and sedation during flexible bronchoscopy in adult patients. Chest. 2011;140(5):1342–1350. doi: 10.1378/chest.10-3361. - DOI - PubMed
    1. José RJ, Shaefi S, Navani N. Sedation for flexible bronchoscopy: current and emerging evidence. Eur Respir Rev. 2013;22(128):106. doi: 10.1183/09059180.00006412. - DOI - PMC - PubMed
    1. Becker HD. Bronchoscopy: the past, the present, and the future. Clin Chest Med. 2010;31(1):1–18. doi: 10.1016/j.ccm.2009.11.001. - DOI - PubMed
    1. Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013;68(Suppl 1):i1–i44. doi: 10.1136/thoraxjnl-2013-203618. - DOI - PubMed

Publication types

Associated data