High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study.
BACKGROUND
The mucolytic and antioxidant effects of N-acetylcysteine (NAC) may have great value in COPD treatment. However, beneficial effects have not been confirmed in clinical studies, possibly due to insufficient NAC doses and/or inadequate outcome parameters used. The objective of this study was to investigate high-dose NAC plus usual therapy in Chinese patients with stable COPD.


METHODS
The 1-year HIACE (The Effect of High Dose N-acetylcysteine on Air Trapping and Airway Resistance of Chronic Obstructive Pulmonary Disease-a Double-blinded, Randomized, Placebo-controlled Trial) double-blind trial conducted in Kwong Wah Hospital, Hong Kong, randomized eligible patients aged 50 to 80 years with stable COPD to NAC 600 mg bid or placebo after 4-week run-in. Lung function parameters, symptoms, modified Medical Research Council (mMRC) dyspnea and St. George's Respiratory Questionnaire (SGRQ) scores, 6-min walking distance (6MWD), and exacerbation and admission rates were measured at baseline and every 16 weeks for 1 year.


RESULTS
Of 133 patients screened, 120 were eligible (93.2% men; mean age, 70.8±0.74 years; %FEV1 53.9±2.0%). Baseline characteristics were similar in the two groups. At 1 year, there was a significant improvement in forced expiratory flow 25% to 75% (P=.037) and forced oscillation technique, a significant reduction in exacerbation frequency (0.96 times/y vs 1.71 times/y, P=.019), and a tendency toward reduction in admission rate (0.5 times/y vs 0.8 times/y, P=.196) with NAC vs placebo. There were no significant between-group differences in mMRC dypsnea score, SGRQ score, and 6MWD. No major adverse effects were reported.


CONCLUSIONS
In this study, 1-year treatment with high-dose NAC resulted in significantly improved small airways function and decreased exacerbation frequency in patients with stable COPD.


BACKGROUND
ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov.
Kwong Wah Hospital, Hong Kong, China. Electronic address: drhoinam@gmail.com.
Hoi Nam
HN
Tse
Medical Department, Innovation & Medical Sciences, Zambon Company SpA, Bresso, Italy.
Luca
L
Raiteri
Wong Tai Sin Hospital, Hong Kong, China.
King Ying
KY
Wong
Wong Tai Sin Hospital, Hong Kong, China.
Kwok Sang
KS
Yee
Kwong Wah Hospital, Hong Kong, China.
Lai Yun
LY
Ng
Kwong Wah Hospital, Hong Kong, China.
Ka Yan
KY
Wai
Kwong Wah Hospital, Hong Kong, China.
Ching Kong
CK
Loo
Kwong Wah Hospital, Hong Kong, China.
Ming Houng
MH
Chan
D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004417:Dyspnea / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006723:Hong Kong; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology
D000975:Antioxidants; D000111:Acetylcysteine