A Double-Blind Randomized Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- The difference in mean PaO2 and the change of PaO2
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
N-acetylcysteine
干预措施: N-acetylcysteine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The difference in mean PaO2 and the change of PaO2
时间窗: day 7; from day 0 to day 7
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.
次要结局
- The change in PaO2/FiO2 ratio(from baseline to day 7)
- The Change in the grade of wheeze assessment (Grading system)(from baseline to day 7)
- The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale(from baseline to day 7)
- The Change in COPD Assessment Test (CAT) score(from baseline to day 7)
- The change in sputum volume(from baseline to day 7)
- The change in FEV1(from baseline to day 7)
- The Change in Leicester cough questionnaire (LCQ) score(from baseline to day 7)
- The 28- and 90-day mortality(from baseline to 28- and 90-day)
- The change in end tidal CO2(from baseline to day 7)
- The change in SaO2(from baseline to day 7)
- The change in PaCO2(from baseline to day 7)
- The time to wean off supplemental oxygen(from baseline to day 7)
- The blood inflammatory markers(from baseline to day 7)
- The length of stay(from baseline to day 7)
研究者
Kwok Wang Chun
Clinical Assistant Professor, Honorary Specialist
Queen Mary Hospital, Hong Kong