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.
Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.
Jin-Ping
JP
Zheng
Jian
J
Kang
Shao-Guang
SG
Huang
Ping
P
Chen
Wan-Zen
WZ
Yao
Lan
L
Yang
Chun-Xue
CX
Bai
Chang-Zheng
CZ
Wang
Chen
C
Wang
Bao-Yuan
BY
Chen
Yi
Y
Shi
Chun-Tao
CT
Liu
Ping
P
Chen
Qiang
Q
Li
Zhen-Shan
ZS
Wang
Yi-Jiang
YJ
Huang
Zhi-Yang
ZY
Luo
Fei-Peng
FP
Chen
Jian-Zhang
JZ
Yuan
Ben-Tong
BT
Yuan
Hui-Ping
HP
Qian
Rong-Chang
RC
Zhi
Nan-Shan
NS
Zhong
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