A Randomised Controlled Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis in Patients With Pseudomonas Aeruginosa
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- The primary endpoint of this study is a reduction in cough at 3 months compared to baseline as measured by the Leicester Cough Questionnaire score.
研究概览
简要总结
Statins are a class of drug used to prevent heart attacks and strokes by lowering blood cholesterol levels. They have also been found to have a beneficial "side effect" of lowering the level of inflammation in the body. This is thought to be one of the reasons they are effective in treating heart attacks and strokes. Laboratory experiments have shown that statins reduce lung inflammation in response to bacteria and this is a promising development for the treatment of chest infections.
Bronchiectasis is a chronic disabling lung disease characterised by chronic sputum production and recurrent chest infections. 2/3 of patients are chronically colonised with bacteria (normally the lungs are sterile) and this leads inflammation in the lung and in the rest of the body.
There are no effective treatments for bronchiectasis other than antibiotics for chest infections. With increasing antibiotic use, there is increasing antibiotic resistance and new treatments for this disease are needed.
The investigators intend to study Atorvastatin in patients with bronchiectasis with colonization with pseudomonas aeruginosa. The investigators will give Atorvastatin to 16 patients with this disease while 16 patients will receive placebo. This will be a crossover study where patients will receive atorvastatin or placebo for 3 months, followed by a statin wash out period of 6 weeks. Thereafter the groups will cross over and the group receiving atorvastatin will now receive placebo and those receiving placebo will receive atorvastatin for 3 months. The investigators will measure inflammation in their lungs and in the rest of their body before and after treatment with atorvastatin. The investigators will also assess their quality of life and number of chest infections over a 7.5 month period.
This pilot study will determine if there is any role for statins are an anti-inflammatory agent in patients with bronchiectasis.
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 We 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
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-80 will be recruited.
- •All will have an established radiological diagnosis of bronchiectasis (CT of the chest).
- •Patients colonised with Pseudomonas Aeruginosa.
- •Able to give informed consent.
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
研究组 & 干预措施
ATORVASTATIN
Atorvastatin 80mg once daily for 3 months, 1.5 month wash out, then Placebo for 3 months
干预措施: ATORVASTATIN (Drug)
PLACEBO
Placebo 3 months, then washout for 1.5 months, then Atorvastatin 80mg once daily
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 3 months compared to baseline as measured by the Leicester Cough Questionnaire score.
时间窗: 7.5 months
次要结局
- pulmonary physiology and assessment of exercise capacity(7.5 months)
- qualitative and quantitative bacteriology(7.5 months)
- health related quality of life and health care utilisation(7.5 months)
- 24 hour sputum volume(7.5 months)
- exacerbation frequency(7.5 months)
- safety of statin therapy(7.5 months)
- Airways and systemic inflammation(7.5 months)