A Randomised Controlled Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- The primary endpoint of this study is a reduction in cough at 6 months compared to baseline as measured by the Leicester Cough Questionnaire score.
研究概览
简要总结
The investigators hypothesise that long term statin treatment will improve patients' symptoms through its anti-inflammatory effect. The beneficial effects on patient symptoms (cough, sputum volume, bacterial load, airway function, exercise tolerance, exacerbation frequency and health related quality of life) will be consequent on reduced neutrophilic airways inflammation.
详细描述
BACKGROUND AND RATIONAL FOR STUDY Bronchiectasis is a chronic debilitating respiratory condition. Patients suffer daily cough, excess sputum production and recurrent chest infections because of inflamed and permanently damaged airways. It is a common with a Scottish incidence of 1 in 1,000 to 1 in 10,000. Over 600 patients in Edinburgh are monitored in secondary care. They frequently utilise primary and secondary care resources through consultations, A&E attendances and inpatient admissions. The economic burden is huge- hospital admissions alone for bronchiectasis cost NHS Lothian just over 1 million pounds alone last year.
LIMITATIONS OF TREATMENT There are few evidence based long term treatments currently available. Long term antibiotics are a feasible option, but with the increasing problems of antimicrobial resistance and side effects, in particular Clostridium difficile and methicillin resistant Staphylococcus aureus (MRSA), there is an international drive to reduce antibiotic usage. There is an urgent need for novel non antibiotic treatments.
Statins as a potential new non antibiotic treatment in bronchiectasis Excessive neutrophilic airways inflammation is the central feature of bronchiectasis. This paradoxically both promotes bacterial colonisation and perpetuates damage to the airways creating a vicious cycle of bacterial colonisation and inflammation.1-3
Statins have been shown to have powerful anti-inflammatory effects.4-6 In animal models, statins can reduce neutrophil recruitment to the inflamed lung and reduce protease activity.7 Statin treatment has been shown to reduce epithelial cell adherence and invasion by Streptococcus pneumoniae in-vitro suggesting a role for statins in preventing bacterial colonisation.8 In healthy controls exposed to lipopolysaccharide to induce acute lung inflammation, pre-treatment with simvastatin reduced neutrophil accumulation in the lung and inhibited production of myeloperoxidase, tumour necrosis factor-alpha, matrix metalloproteinases and C-reactive protein.9 There was also an increase in neutrophil apoptosis, suggesting that statins may aid the resolution of inflammation in the airway.10
STUDY HYPOTHESIS The investigators hypothesise that long term statin treatment will improve patients' symptoms through its anti-inflammatory effect. The beneficial effects on patient symptoms (cough, sputum volume, bacterial load, airway function, exercise tolerance, exacerbation frequency and health related quality of life) will be consequent on reduced neutrophilic airways inflammation.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-75 will be recruited. All will have an established radiological diagnosis of bronchiectasis (CT of the chest). Patients will have clinically significant bronchiectasis expectorating mucopurulent or purulent sputum when clinically stable with at least 2 chest infections per year.
排除标准
- •current smokers or ex-smokers of less than 1 year; >15 pack year history
- •cystic fibrosis
- •active allergic bronchopulmonary aspergillosis
- •active tuberculosis
- •poorly controlled asthma
- •pregnancy or breast feeding
- •known allergy to statins
- •active malignancy
- •chronic liver disease
- •established cardiovascular or cerebrovascular disease
- •statin use in the last year
- •patients on long term oral macrolides due to the interaction with statin therapy patients chronically colonised with Pseudomonas aeruginosa (defined as two or more isolates of Pseudomonas aeruginosa whilst clinically stable in 6 months prior to the study).
研究组 & 干预措施
Atorvastatin
Atorvastatin 80mg once daily
干预措施: Atorvastatin (Drug)
Placebo
Placebo
干预措施: Atorvastatin (Drug)
结局指标
主要结局
The primary endpoint of this study is a reduction in cough at 6 months compared to baseline as measured by the Leicester Cough Questionnaire score.
时间窗: 6 months
次要结局
- pulmonary physiology and assessment of exercise capacity(6 months)
- 24 hour sputum volume(6 months)
- qualitative and quantitative bacteriology(6 months)
- health related quality of life and health care utilisation(6 months)
- exacerbation frequency(6 months)
- safety of statin therapy(6 months)
- assessment of airways and systemic inflammation(6 months)