The Effect of High Dose N-acetylcysteine on Airtrapping and Airway Resistance in Chronic Obstructive Pulmonary Disease (COPD) Patients

The Effect of High Dose N-acetylcysteine on Airtrapping and Airway Resistance of Chronic Obstructive Pulmonary disease-a Double Blinded Randomized Placebo Controlled Trial

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 Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Placebo; Drug: N-acetycysteine (600mg twice daily)

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

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Medical department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (600mg twice daily)	Drug: Placebo; Placebo (600mg twice daily)
Active Comparator: N-acetylcysteine; N-acetylcysteine (600mg twice daily)	Drug: N-acetycysteine (600mg twice daily); N-acetycysteine (600mg twice daily) for one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airtrapping in COPD patients	The airtrapping of COPD patients is measured by inspiratory capacity (IC), using plethsmography (MedGraphics Elite series)	At baseline (time 0 week)
Airtrapping in COPD patients	The airtrapping of COPD patients is measured by inspiratory capacity (IC), using plethsmography (MedGraphics Elite series)	At 16th week
Airtrapping in COPD patients	The airtrapping of COPD patients is measured by inspiratory capacity (IC), using plethsmography (MedGraphics Elite series)	At 52th Week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway resistance in COPD patients	Airway resistance is measured by plethsmography (Medgraphics Elite series) and impulse oscillometry.	At baseline ( time 0)
Airway resistance in COPD patients	Airway resistance is measured by plethsmography (Medgraphics Elite series) and impulse oscillometry.	At 16th week
Airway resistance in COPD patients	Airway resistance is measured by plethsmography (Medgraphics Elite series) and impulse oscillometry.	At 52th week
Exercise capacity	Exercise capacity is measured by 6-min-walking distance (6MWD)and it is performed by a trained physiotherapist	At baseline ( time 0)
Exercise capacity	Exercise capacity is measured by 6-min-walking distance (6MWD)and it is performed by a trained physiotherapist	At 16th week
Exercise capacity	Exercise capacity is measured by 6-min-walking distance (6MWD)and it is performed by a trained physiotherapist	At 52th week
Quality of life	Quality of life is assessed by using the St Qeorge Respiratory Questionnaire (SQRQ)and it will be performed by a trained physiotherapist	At baseline (time 0)
Quality of life	Quality of life is assessed by using the St Qeorge Respiratory Questionnaire (SQRQ)and it will be performed by a trained physiotherapist	At 16th week
Quality of life	Quality of life is assessed by using the St Qeorge Respiratory Questionnaire (SQRQ)and it will be performed by a trained physiotherapist	At 52th week
COPD exacerbation rate	The number of COPD exacerbation (exacerbation was defined as 2 out of 3 of the following criteria; 1.increase in shortness of breath, 2. increase in sputum purulence or 3. increase in sputum volume) will be assessed and documented	At 52th week

Collaborators and Investigators

• Sponsor: Kwong Wah Hospital
• Investigators: Principal Investigator: Hoi Nam Tse, FHKAM, MBChB, Kwong Wah Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: June 1, 2010
• First Submitted That Met QC Criteria: June 2, 2010
• First Posted (Estimate): June 3, 2010

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: COPD; N-acetylcysteine; airtrapping; airway resistance; antioxidant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: KW/EX/09-140; PR/CT 324/2009 (Other Identifier: Department of Health, Hong Kong)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No