Clinical trial NCT01136239: The Effect of High Dose N-acetylcysteine on Airtrapping and Airway Resistance in Chronic Obstructive Pulmonary Disease (COPD) Patients
Official title: The Effect of High Dose N-acetylcysteine on Airtrapping and Airway Resistance of Chronic Obstructive Pulmonary disease-a Double Blinded Randomized Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COPD
Keywords: COPD
N-acetylcysteine
airtrapping
airway resistance
antioxidant
Lead sponsor: Kwong Wah Hospital
Sponsor class: OTHER
First posted: 2010-06-03
Enrollment: 133
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to investigate the add-on effect of high dose NAC (600mg tablet twice daily) on reduction of airtrapping and airway resistance in stable COPD patients as well as to study it's effect in reducing exacerbation, improving exercise capacity and quality of life in stable COPD patients.

Detailed description: Background: The mucolytic and antioxidant effects of N-acetylcysteine (NAC) may be of great value in treatment of COPD patients. However, previous studies fail to demonstrate the beneficial effect of NAC. This may be due to insufficient dose of NAC used as well as inadequate outcome parameters measured in the past studies.

Objective of study: This study is to investigate the add-on effect of high dose NAC (600mg tablet twice daily) on reduction of airtrapping and airway resistance in stable COPD patients as well as to study it's effect in reducing exacerbation, improving exercise capacity and quality of life in stable COPD patients.

Study design: Randomized double blinded placebo controlled trial in Kwong Wah Hospital

Methodology: Patients are recruited in Kwong Wah Hospital if they fulfill the spirometric criteria of COPD. Eligible subjects will be randomized into the treatment (NAC 600mg tablet twice daily) and placebo group after completion of run in period. NAC and placebo will be prescribed accordingly in addition to their usual therapy. Both patients and investigators are blinded about the group allocation. Baseline assessment will be done and patients will be followed up at 16th weeks and 52th week of the study.

During each follow-up visit, hyperinflation parameters like inspiratory capacity (IC) will be measured by plethysmography. Airway resistance will be measured by both plethysmography and impulse oscillometry machine. Exercise capacity (6 min walking distance) and quality of life are also recorded during each follow up.

The difference of the above parameters between the 2 groups (drug and placebo group) will be analyszed by the Repeated measures ANOVA test

Eligibility criteria: Inclusion Criteria:

* Spirometry diagnosed COPD with FEV1/FVC ratio less than 70% and FEV1 less than 80% predicted
* clinically stable and exacerbation free in the past 4 weeks
* history of at least one COPD exacerbation in the past one year

Exclusion Criteria:

* patients allergic or intolerant to NAC
* Recent use of NAC in the past one month
* history of asthma, non COPD respiratory disorders like bronchiectasis, pneumoconiosis or any active pulmonary infection
* patients on long term steroid
* patients on long term oxygen therapy or non invasive ventilation

Primary outcomes:
measure: Airtrapping in COPD patients
timeFrame: At baseline (time 0 week)
measure: Airtrapping in COPD patients
timeFrame: At 16th week
measure: Airtrapping in COPD patients
timeFrame: At 52th Week
Secondary outcomes:
measure: Airway resistance in COPD patients
timeFrame: At baseline ( time 0)
measure: Airway resistance in COPD patients
timeFrame: At 16th week
measure: Airway resistance in COPD patients
timeFrame: At 52th week
measure: Exercise capacity
timeFrame: At baseline ( time 0)
measure: Exercise capacity
timeFrame: At 16th week
measure: Exercise capacity
timeFrame: At 52th week
measure: Quality of life
timeFrame: At baseline (time 0)
measure: Quality of life
timeFrame: At 16th week
measure: Quality of life
timeFrame: At 52th week
measure: COPD exacerbation rate
timeFrame: At 52th week
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Medical Department
Study officials:
affiliation: Kwong Wah Hospital
name: Hoi Nam Tse, FHKAM, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tse HN, Raiteri L, Wong KY, Ng LY, Yee KS, Tseng CZS. Benefits of high-dose N-acetylcysteine to exacerbation-prone patients with COPD. Chest. 2014 Sep;146(3):611-623. doi: 10.1378/chest.13-2784.
citation: Tse HN, Raiteri L, Wong KY, Yee KS, Ng LY, Wai KY, Loo CK, Chan MH. High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest. 2013 Jul;144(1):106-118. doi: 10.1378/chest.12-2357.