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

NCT05706402 | Unknown Phase 3 DMC

• 1 other identifier: UW 22-710
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

N-acetylcysteine; Chronic Obstructive Pulmonary Disease; Chronic Obstructive Pulmonary Disease exacerbation; Clinical trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• The change in PaO2/FiO2 ratio

  from baseline to day 7

• The change in sputum volume

  from baseline to day 7

• The Change in COPD Assessment Test (CAT) score

  from baseline to day 7

• The Change in Leicester cough questionnaire (LCQ) score

  from baseline to day 7

• The Change in the grade of wheeze assessment (Grading system)

  from baseline to day 7

Study Arms (2)

N-acetylcysteine

EXPERIMENTAL

Drug: N-acetylcysteine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

N-acetylcysteine 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.

N-acetylcysteine

Placebo 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.

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 40 years or above, either male or female.
• 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.
• 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.
• Patients who consent to join this clinical trial

You may not qualify if:

• Patients who are on long-term NAC treatment
• Patients who are not able to take NAC including drug allergy
• Patients with other co-existing respiratory diseases including but not limited to asthma, interstitial lung diseases, and bronchiectasis
• Patients on non-invasive or invasive mechanical ventilation where oral medication is not allowed
• Patients on long term macrolide treatment
• Patients on macrolide as antibiotics for COPD exacerbation

Sponsors & Collaborators

• Queen Mary Hospital, Hong Kong: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (1)

• 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.

  PMID: 39108325 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Wang Chun Kwok, MBBS

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wang Chun Kwok, MBBS

CONTACT

+852 2255 5336; herbert728@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor, Honorary Specialist

Model Details: This study is a double-blind randomised controlled trial on NAC as an adjunctive treatment for acute COPD exacerbation. The randomization will be done via computer software with half of the patients randomized to received oral NAC (600 mg twice daily) and half receive placebo, with randomization ratio being 1 to 1. Patients in the two randomised group will be asked to participate in the study for a maximum of 1 week.

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 31, 2023
• Study Start: September 18, 2023
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)