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

NCT ID: NCT05706402

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-18
• Study Completion Date: 2025-09-30

Brief 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.

Detailed 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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

N-acetylcysteine

Group Type: EXPERIMENTAL

N-acetylcysteine

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Queen Mary Hospital, Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Kwok Wang Chun

Clinical Assistant Professor, Honorary Specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wang Chun Kwok, MBBS

Role: PRINCIPAL_INVESTIGATOR

Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong

Locations

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Wang Chun Kwok, MBBS

Role: CONTACT

herbert728@gmail.com

+852 2255 5336

Facility Contacts

Wang Chun Kwok

Role: primary

References

Kwok WC, Chan SKS, Chiang KY, Ho CMJ. A double-blind randomized controlled trial of N-acetylcysteine (NAC) for the treatment of acute exacerbation of chronic obstructive pulmonary disease. Respirol Case Rep. 2024 Aug 6;12(8):e01449. doi: 10.1002/rcr2.1449. eCollection 2024 Aug.

Reference Type: DERIVED

PMID: 39108325 (View on PubMed)

Other Identifiers

UW 22-710

Identifier Type: -

Identifier Source: org_study_id