Clinical trial NCT05706402: N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of COPD
Official title: A Double-Blind Randomized Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: N-acetylcysteine
Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease exacerbation
Clinical trial
Lead sponsor: Queen Mary Hospital, Hong Kong
Sponsor class: OTHER
First posted: 2023-01-31
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The difference in mean PaO2 and the change of PaO2
timeFrame: day 7; from day 0 to day 7
Secondary outcomes:
measure: The change in PaO2/FiO2 ratio
timeFrame: from baseline to day 7
measure: The change in sputum volume
timeFrame: from baseline to day 7
measure: The Change in COPD Assessment Test (CAT) score
timeFrame: from baseline to day 7
measure: The Change in Leicester cough questionnaire (LCQ) score
timeFrame: from baseline to day 7
measure: The Change in the grade of wheeze assessment (Grading system)
timeFrame: from baseline to day 7
measure: The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale
timeFrame: from baseline to day 7
measure: The change in FEV1
timeFrame: from baseline to day 7
measure: The change in end tidal CO2
timeFrame: from baseline to day 7
measure: The change in SaO2
timeFrame: from baseline to day 7
measure: The change in PaCO2
timeFrame: from baseline to day 7
measure: The time to wean off supplemental oxygen
timeFrame: from baseline to day 7
measure: The length of stay
timeFrame: from baseline to day 7
measure: The blood inflammatory markers
timeFrame: from baseline to day 7
measure: The 28- and 90-day mortality
timeFrame: from baseline to 28- and 90-day
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
name: Wang Chun Kwok, MBBS
role: PRINCIPAL_INVESTIGATOR
References: