Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD.


METHODS
We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio (FEV(1)/FVC) of less than 0.7 and an FEV(1) between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry (http://umin.ac.jp/ctr/index/htm) number UMIN-CRT C000000233.


RESULTS
354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1.01 [SE 0.06] vs 1.35 [SE 0.06]), risk ratio 0.75 (95% CI 0.62-0.92, p=0.004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated.


CONCLUSIONS
Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD.
Zheng
Jin-Ping
JP
Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.
Kang
Jian
J
Huang
Shao-Guang
SG
Chen
Ping
P
Yao
Wan-Zen
WZ
Yang
Lan
L
Bai
Chun-Xue
CX
Wang
Chang-Zheng
CZ
Wang
Chen
C
Chen
Bao-Yuan
BY
Shi
Yi
Y
Liu
Chun-Tao
CT
Chen
Ping
P
Li
Qiang
Q
Wang
Zhen-Shan
ZS
Huang
Yi-Jiang
YJ
Luo
Zhi-Yang
ZY
Chen
Fei-Peng
FP
Yuan
Jian-Zhang
JZ
Yuan
Ben-Tong
BT
Qian
Hui-Ping
HP
Zhi
Rong-Chang
RC
Zhong
Nan-Shan
NS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002233:Carbocysteine / Q000009:adverse effects / Q000627:therapeutic use*; D002681:China; D004311:Double-Blind Method; D005100:Expectorants / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life
D005100:Expectorants; D002233:Carbocysteine