Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial
- Yumin Zhou
- Fan Wu
- Zhe Shi
- Jie Cao
- Jia Tian
- Weimin Yao
- Liping Wei
- Fenglei Li
- Shan Cai
- Yao Shen
- Zanfeng Wang
- Huilan Zhang
- Yanfan Chen
- Yingyun Fu
- Zhiyi He
- Chun Chang
- Yongliang Jiang
- Shujing Chen
- Changli Yang
- Shu-yan Yu
- Heshen Tian
- Qijian Cheng
- Ziwen Zhao
- Yinghua Ying
- Yong Zhou
- Shengming Liu
- Z. Deng
- Peiyu Huang
- Yunzhen Zhang
- Xiangwen Luo
- Hai-yan Zhao
- J. Gui
- Weiguang Lai
- G. Hu
- Cong Liu
- Ling Su
- Zhiguang Liu
- Jianhui Huang
- Dongxing Zhao
- N. Zhong
- Pixin Ran
- Zhuxiang Sha Zihui Longhui Jinzhen Hailin Yuliang Yu Haiqin Zhao Liu Wang Tang Zheng Zhou Cai Zhang Li Chen Ji
- Zhuxiang Zhao
- Shan Liu
- Zihui Wang
- Longhui Tang
- Jin-Ping Zheng
- Hailin Zhou
- Yuliang Cai
- Yu Zhang
- Haiqing Li
- Ping Chen
- F. Jiang
- Suizheng Cai
- Jian Zhou
- Hong Xia
- Meijia Wang
- Jiaojiao Chu
- Xueding Cai
- Yazhen Li
- Yanfei Bin
- Lingshan Zeng
- Haiqin Zhang
- Hua He
- Yichen He
- Wenxia Zhou
- Li Chen
What this study found
High-dose N-acetylcysteine did not significantly improve the primary outcomes of total exacerbation rate or prebronchodilator FEV1 at 24 months versus placebo. Total exacerbations were 0.65 per patient-year with N-acetylcysteine versus 0.72 with placebo, RR 0.90, 95% CI 0.80 to 1.02, P = 0.10; prebronchodilator FEV1 change at 24 months was 137 ml versus 121 ml, P = 0.72. It did significantly reduce moderate-to-severe exacerbations, 0.34 versus 0.45 per patient-year, RR 0.76, 95% CI 0.64 to 0.90, P = 0.001. Adverse events were similar overall, with 117 events in the N-acetylcysteine group…
- Study & population
- Double-blind, parallel-group, multicentre randomized clinical trial in adults aged 40 to 80 years with mild-to-moderate COPD (GOLD stage 1 to 2) in China.
- Intervention
- N-acetylcysteine 600 mg twice daily for 2 years, compared with matched placebo twice daily.
- Key limitation
- Primary coprimary outcomes were negative, so the main efficacy claim was not confirmed.
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Open PDFOriginal abstract
Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80–1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604. Evidence for the treatment of patients with mild-to-moderate COPD is limited. Here, the authors show that long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improve lung function in patients with mild-tomoderate COPD.