Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty

Zeguang Zheng; Kai Yang; Ni Liu; Xiuhua Fu; Huijie He; Hong Chen; Peijun Xu; Jing Wang; Maofeng Liu; Yuling Tang; Fengzi Zhao; Shufeng Xu; Xiaowei Yu; Jichang Han; Bo Yuan; Bin Jia; Guifen Pang; Yantong Shi; Min Kuang; Haiyan Shao; Hao Xiong; Jia He; Yuanyuan Pan; Rongchang Chen

doi:10.3389/fmed.2023.1182602

Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty

Front Med (Lausanne). 2023 May 25:10:1182602. doi: 10.3389/fmed.2023.1182602. eCollection 2023.

Authors

Zeguang Zheng¹, Kai Yang², Ni Liu¹, Xiuhua Fu³, Huijie He⁴, Hong Chen⁵, Peijun Xu⁶, Jing Wang⁷, Maofeng Liu⁸, Yuling Tang⁹, Fengzi Zhao¹⁰, Shufeng Xu¹¹, Xiaowei Yu¹², Jichang Han¹³, Bo Yuan¹⁴, Bin Jia¹⁵, Guifen Pang¹⁶, Yantong Shi¹⁷, Min Kuang¹⁸, Haiyan Shao¹⁹, Hao Xiong²⁰, Jia He²¹, Yuanyuan Pan²², Rongchang Chen²

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital (First Affiliated Hospital of South University of Science and Technology and Second Affiliated Hospital of Jinan University), Shenzhen, China.
³ The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
⁴ The First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and Technology, Baotou, China.
⁵ The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁶ Zibo Central Hospital, Zibo, China.
⁷ The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁸ PKU Care Luzhong Hospital, Zibo, China.
⁹ The First Hospital of Changsha, Changsha, China.
¹⁰ The First Hospital of Qiqihar, Qiqihar, China.
¹¹ First Hospital of Qinhuangdao, Qinhuangdao, China.
¹² Changzhou No.2 People's Hospital, Changzhou, China.
¹³ Huaihe Hospital of Henan University, Kaifeng, China.
¹⁴ Siping Central People's Hospital, Siping, China.
¹⁵ The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
¹⁶ Affiliated Hospital of Chengde Medical University, Chengde, China.
¹⁷ People's Hospital of Rizhao, Rizhao, China.
¹⁸ The Second Nanning People's Hospital, Nanning, China.
¹⁹ The First People's Hospital of Wenling, Wenling, China.
²⁰ The Second People's Hospital of Yibin, Yibin, China.
²¹ Department of Health Statistics, Faculty of Medical Service, Naval Medical University, Shanghai, China.
²² Yingu Pharmaceutical Co Ltd., Beijing, China.

Abstract

Background: Ambroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance.

Methods: This study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population.

Results: Between 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: -0.29; 95% CI: -0.53 to -0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: -0.18; 95% CI: -0.34 to -0.03; p = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported.

Discussion: In hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo.

Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].

Keywords: efficacy; expectoration difficulty; inhaled ambroxol; lower respiratory tract infection; mucopurulent sputum; safety.