Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive
pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled
trial.
Author(s): Zheng JP(1), Wen FQ(2), Bai CX(3), Wan HY(4), Kang J(5), Chen P(6), Yao WZ(7), Ma
LJ(8), Li X(9), Raiteri L(10), Sardina M(10), Gao Y(1), Wang BS(11), Zhong
NS(12); PANTHEON study group.
Affiliation(s): Author information:
(1)State Key Laboratory of Respiratory Disease, National Clinical Research Center
for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First
Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
(2)West China Hospital, Sichuan University, Chengdu, China.
(3)Zhongshan Hospital, Fudan University, Shanghai, China.
(4)Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai,
China.
(5)First Affiliated Hospital of China Medical University, Shenyang, China.
(6)Shenyang PLA General Hospital, Shenyang, China.
(7)Peking University Third Hospital, Beijing, China.
(8)Henan Provincial People's Hospital, Zhengzhou, China.
(9)Hainan Zambon Pharmaceutical, Beijing, China.
(10)Innovation & Medical Sciences Department, Zambon, Bresso, Milan, Italy.
(11)MedKey Med-Tec Development, Shanghai, China.
(12)State Key Laboratory of Respiratory Disease, National Clinical Research Center
for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First
Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic
address: nanshan@vip.163.com.
Publication date & source: 2014, Lancet Respir Med. , 2(3):187-94
BACKGROUND: Increased oxidative stress and inflammation has a role in the
pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with
antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might
provide a useful therapeutic approach for COPD. We aimed to assess whether
N-acetylcysteine could reduce the rate of exacerbations in patients with COPD.
METHODS: In our prospective, randomised, double-blind, placebo-controlled,
parallel-group study, we enrolled patients aged 40-80 years with
moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s
[FEV1]/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34
hospitals in China. We stratified patients according to use of inhaled
corticosteroids (regular use or not) at baseline and randomly allocated them to
receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for
1 year. The primary endpoint was the annual exacerbation rate in patients who
received at least one dose of study drug and had at least one assessment visit
after randomisation. This study is registered with the Chinese Clinical Trials
Registry, ChiCTR-TRC-09000460.
FINDINGS: Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of
whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to
placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the
N-acetylcysteine group who received at least one dose and had at least one
assessment visit (1·16 exacerbations per patient-year) and 641 acute
exacerbations in 482 patients in the placebo group (1·49 exacerbations per
patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was
well tolerated: 146 (29%) of 495 patients who received at least one dose of
N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495
patients who received at least one dose of placebo (46 serious). The most common
serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495
patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo
group.
INTERPRETATION: Our findings show that in Chinese patients with
moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can
prevent exacerbations, especially in disease of moderate severity. Future studies
are needed to explore efficacy in patients with mild COPD (GOLD I).
FUNDING: Hainan Zambon Pharmaceutical.
Erratum in
Lancet Respir Med. 2014 Apr;2(4):e4.
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