title: Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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).
  
  
  BACKGROUND
  Hainan Zambon Pharmaceutical.
authors.affiliation: 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.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Zheng
authors.affiliation: West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Wen
authors.affiliation: Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chun-Xue
authors.initials: CX
authors.lastname: Bai
authors.affiliation: Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huan-Ying
authors.initials: HY
authors.lastname: Wan
authors.affiliation: First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Shenyang PLA General Hospital, Shenyang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Peking University Third Hospital, Beijing, China.
authors.forename: Wan-Zhen
authors.initials: WZ
authors.lastname: Yao
authors.affiliation: Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Ma
authors.affiliation: Hainan Zambon Pharmaceutical, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Innovation & Medical Sciences Department, Zambon, Bresso, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Raiteri
authors.affiliation: Innovation & Medical Sciences Department, Zambon, Bresso, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sardina
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: MedKey Med-Tec Development, Shanghai, China.
authors.forename: Bai-Song
authors.initials: BS
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Zhong
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine