N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Double-Blind Randomized Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05706402
• Other study ID #: UW 22-710
• Status: Recruiting
• Phase: Phase 3
• Start date: September 18, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: November 2023
• Source: Queen Mary Hospital, Hong Kong
• Contact: Wang Chun Kwok, MBBS
• Phone: +852 2255 5336
• Email: herbert728[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with Chronic obstructive pulmonary disease (COPD) experience gradually deteriorating lung function, which may be complicated by acute exacerbations. N- acetylcysteine (NAC) is frequently used in patients with COPD as a mucolytic. Besides its mucolytic effects, high-dose NAC has additional benefits in patients with stable COPD, including improving lung function and reducing exacerbations. Studies on the dose-dependent effects of NAC in COPD patients showed a high dose of NAC was needed to achieve its antioxidant effects and clinical benefits in COPD patients, whereas a dose of 600 mg once daily was not able to increase glutathione levels. According to a study conducted in Hong Kong on patients with stable COPD, 1 year of treatment with high-dose NAC at 600 mg twice daily improved small airways function in terms of forced expiratory flow and forced oscillation technique, and also significantly reduced exacerbation frequency with a decreasing trend in admission rate. In a meta-analysis, patients treated with NAC had significantly and consistently fewer exacerbations of COPD. The role of NAC was examined in a Delphi consensus study involving 53 COPD experts from 12 countries. Respondents agreed that regular treatment with mucolytic agents could effectively decrease the frequency of exacerbations and the duration of mild-to-moderate exacerbations, while delaying the time to first exacerbation and increasing symptom-free time in COPD patients. The panel also approved the doses of NAC with favourable side effect profiles to be recommended for regular use in patients with a bronchitic phenotype.

However, there have been conflicting results regarding the efficacy of NAC for treating acute exacerbation of COPD. NAC has not been included as an adjunct for the treatment of COPD exacerbation in international guidelines. As NAC is relatively low cost, readily available, and has a favourable side effect profile as a treatment for COPD exacerbation, it is important to properly assess the clinical benefits of NAC as an adjunct to standard medical treatments to hasten recovery. This study is a double-blind randomised controlled trial on NAC as an adjunctive treatment for acute COPD exacerbation. It will assess the role of NAC in the treatment of acute COPD exacerbation.

Description:

The aim of the study is to assess the role of NAC in the treatment of acute COPD exacerbation in terms of clinical, physiological, and laboratory parameters, including PaO2, PaO2/FiO2 ratio, PaCO2, SaO2, end tidal CO2, length of stay, coughing, wheezing, dyspnoea, need for supplemental oxygen sputum volume, FEV1, and blood inflammatory markers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Aged 40 years or above, either male or female.

2. Patients who are current or ex-smokers

• Ever-smoker is defined as having smoked at least one cigarette, pipe, water pipe, cigars, or hand rolled cigarettes a day for 1 or more years.

3. Patients with a pre-existing diagnosis of COPD admitted to the general medical and respiratory subspecialty wards for acute COPD exacerbation

• COPD is defined as dyspnoea and/or chronic productive cough with spirometry confirmation of persistent airflow limitation at FEV1/FVC less than 70%.

• COPD acute exacerbation is defined as an acute increase in symptoms (one or more of the following: cough frequency and severity, sputum production, dyspnoea) beyond normal day-to-day variations leading to a change in medication.

4. Patients who consent to join this clinical trial

Exclusion Criteria:

1. Patients who are on long-term NAC treatment

2. Patients who are not able to take NAC including drug allergy

3. Patients with other co-existing respiratory diseases including but not limited to asthma, interstitial lung diseases, and bronchiectasis

4. Patients on non-invasive or invasive mechanical ventilation where oral medication is not allowed

5. Patients on long term macrolide treatment

6. Patients on macrolide as antibiotics for COPD exacerbation

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• N-acetylcysteine
Patients will be randomized to receive oral N-acetylcysteine at 600 mg twice daily for 1 week. The randomization will be done via computer software with half of the patients randomized to receive NAC. Patients will also be given standard treatment for your COPD exacerbation and can continue the use of usual inhalers for COPD.
• Placebo
Patients will be randomized to receive placebo for 1 week. The randomization will be done via computer software with half receive placebo. Patients will also be given standard treatment for your COPD exacerbation and can continue the use of usual inhalers for COPD.

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary Hospital, Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference in mean PaO2 and the change of PaO2	The co-primary endpoint of interest is the difference in mean PaO2 on day 7 of treatment and the change of PaO2 from day 0 to day 7.	day 7; from day 0 to day 7
Secondary	The change in PaO2/FiO2 ratio	The change in PaO2/FiO2 ratio from baseline to day 7	from baseline to day 7
Secondary	The change in sputum volume	The change in sputum volume on days 4 and 7	from baseline to day 7
Secondary	The Change in COPD Assessment Test (CAT) score	The change in CAT score on days 4 and 7. CAT score has a scoring range of 0 to 40. Higher scores indicating the COPD has a greater impact on overall health outcome.	from baseline to day 7
Secondary	The Change in Leicester cough questionnaire (LCQ) score	The change in LCQ score on days 4 and 7. The LCQ is assessing 3 domains (physical, psychological and social). The total score range is 3-21 and domain scores range from 1-7. Higher scores indicates a better quality of life.	from baseline to day 7
Secondary	The Change in the grade of wheeze assessment (Grading system)	The change in grade of wheeze on days 4 and 7. Grade of wheeze, to be assessed by the PI or Co-I, is a simple bedside assessment can that can assess the severity of COPD. This could allow a simple assessment of the respiratory status for the patients with COPD exacerbation. There will be 3 grades; higher grade indicates a more severe respiratory symptoms.	from baseline to day 7
Secondary	The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale	The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale on days 4 and 7. The mMRC scale ranges from grade 0 to 4. Higher grade indicates a higher degree of baseline functional disability due to dyspnoea.	from baseline to day 7
Secondary	The change in FEV1	The change in FEV1 on days 4 and 7	from baseline to day 7
Secondary	The change in end tidal CO2	The change in end tidal CO2 on days 4 and 7	from baseline to day 7
Secondary	The change in SaO2	The change in SaO2 on days 4 and 7	from baseline to day 7
Secondary	The change in PaCO2	The change in PaCO2 on day 7	from baseline to day 7
Secondary	The time to wean off supplemental oxygen		from baseline to day 7
Secondary	The length of stay		from baseline to day 7
Secondary	The blood inflammatory markers	Blood inflammatory markers including white cell count, neutrophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and high-sensitivity CRP (hs-CRP) will also be measured, total 20 mL of blood will be taken. Blood inflammatory markers including white cell count, neutrophil count, ESR, CRP, and hs-CRP will be measured on days 4 and 7. The blood tests arranged for the patients are the basic blood tests for clinical management of COPD exacerbation and it does not involve extra blood testing for the patients.	from baseline to day 7
Secondary	The 28- and 90-day mortality		from baseline to 28- and 90-day