A double-blind randomized controlled trial of N-acetylcysteine (NAC) for the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with acute exacerbation (AECOPD) being a common sequalae which negatively impact health status, rates of hospitalization and readmission, and disease progression. N-acetylcysteine (NAC) has been studied in COPD in both stable state and acute exacerbations, which has been shown to have small beneficial effects in stable COPD, as well as AECOPD. Yet, there has been lack of study with well-designed protocol to assess the role of NAC in more objective outcomes in AECOPD.

Methods: This is a double-blind randomized controlled trial. Patients will be randomized in 1:1 ratio to receive oral NAC at 600 mg twice daily or placebo twice daily with standard of care. Partial pressure of oxygen (PaO₂), partial pressure of carbon dioxide (PaCO₂) and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO₂/FiO₂) will be measured on days 1 and 7. The following will be measure at baseline and on day 4 and 7: Forced expiratory volume in one second (FEV₁), 24-hour sputum volume, oxygen saturation (SaO₂), end-tidal CO₂, Leicester Cough Questionnaire (LCQ) score, COPD Assessment Test (CAT) score, grading of wheeze and grade of dyspnoea; blood inflammatory markers (leucocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and high sensitivity CRP (hs-CRP)). Patients will be randomized to oral NAC at 600 mg twice daily or placebo for 7 days. The main outcome measures include: The difference in PaO₂ on day 7. Secondary outcome: Change in following parameters on day 4/7 from baseline: FEV₁, sputum volume, CAT score, LCQ score, SaO₂, grade of wheeze; mMRC Dyspnoea Scale, end-tidal CO₂, blood inflammatory marker, change in PaO₂/FiO₂ ratio from baseline to day 7, PaCO₂ on day 7, 28 and 90 days' mortality, time to wean off supplemental oxygen, length of stay.Primary and secondary outcomes will be compared among the two treatment groups with two-sample t-test.

Discussion: We hypothesize that NAC use in COPD exacerbation can provide benefits in clinical and laboratory parameters.

Trial registration: Name of the registry : ClinicalTrials.gov Trial registration number : NCT05706402. URL of the trial registry record for this trial : https://classic.clinicaltrials.gov/ct2/show/NCT05706402 Date of registration : Registered on 11th January 2023 Funding of the trial : The Health and Medical Research Fund (HMRF). Name and contact information for the trial sponsor : Wang Chung Kwok, Clinical Assistant Professor, Honorary Associate Consultant, Queen Mary Hospital, The University of Hong Kong, Hong Kong. Role of sponsor : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.