Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Non-cystic Fibrosis Bronchiectasis: a Cross-over, Unicentric, Double-blind and Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Quality of life questionnaire
研究概览
简要总结
Although relatively common, bronchiectasis is considered an orphan disease as there is little evidence for adequate treatment, most of the therapeutic options are extrapolated from studies with patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Inhaled bronchodilators and corticosteroids should be used as a therapeutic test and maintained if there is improvement of symptoms or lung function. There is no evidence to justify the use of mucolytic agents for these patients. The treatment with greater evidence is the use of macrolides, especially azithromycin. A meta-analysis published in 2014 showed that there was a reduction in the number of exacerbations, an improvement in the quality of life and a reduction in the decrease in FEV1. However, studies have shown conflicting results regarding quality of life and pulmonary function.
Roflumilast is a phosphodiesterase-4 inhibitor with an anti-inflammatory effect in vitro and in vivo due to the inhibition of cyclic adenosine monopostat breakdown (cAMP) to its inactive phosphodiesterase form. As this enzyme is expressed in high concentrations in leukocytes and other inflammatory cells responsible for the pathogenesis of pulmonary diseases such as COPD, it has been studied and used for this disease. COPD is characterized by a chronic inflammatory process of the airways, predominantly neutrophils and high levels of proinflammatory cytokines related to this cell, such as interleukin-8, neutrophil elastase, tumor necrosis factor (TNF) alpha and E-selectin. The REACT study showed that roflumilast prevents moderate and severe infectious exacerbations in addition to improved lung function in patients with COPD who continue to exacerbate despite the use of combined bronchodilator and inhaled corticosteroid therapy.
Since bronchiectasis and COPD are chronic inflammatory diseases, they present similar inflammatory processes, with neutrophil as the main inflammatory cell, it is expected that the use of roflumilast also has an anti-inflammatory effect in bronchiectasis. In addition, since bronchiectasis is a disease with poor evidence for pharmacological treatment, it is necessary to search for new therapeutic possibilities.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years;
- •Diagnosis of bronchiectasis by chest tomography;
- •FEV1 <60% of predicted;
- •History of chronic bronchitis (chronic cough and sputum for at least 3 months in the last 2 years);
- •2 or more infectious exacerbations in the last year (defined as worsening of cough and / or dyspnoea and / or decreased general condition, increased quantity and purulence of sputum that required systemic antibiotic use (oral or intravenous).
排除标准
- •Hemoptysis in the last 6 months (significance at the discretion of the investigator);
- •Current or prior smoking if > 10 pack-years;
- •FEV1 < 30% of predicted;
- •Known allergy to roflumilast;
- •Pulmonary exacerbation present or occurring in the last 4 weeks;
- •Child B or C cirrhosis;
- •Active cancer (except basal cell carcinoma);
- •Severe heart failure;
- •Depression associated with suicidal ideation;
- •Pregnancy.
研究组 & 干预措施
Roflumilast
Roflumilast tablets will be supplied at a concentration of 500 mcg. Each tablet contains 500mcg of the active ingredient in addition to the excipients: lactose monohydrate, corn starch, povidone and magnesium stearate. The coating contains hypromellose, macrogol, titanium dioxide, yellow iron oxide. Patients should take 1 tablet once daily, before, during or after meals, at the same time each day.
干预措施: Roflumilast (Drug)
Placebo (control)
Roflumilast placebo-containing tablets will look similar to active roflumilast tablets and will be supplied to patients in packs identical to those of the active drug.
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Quality of life questionnaire
时间窗: 12 weeks
To evaluate the impact of roflumilast on the quality of life of patients with bronchiectasis through the Saint George Respiratory Questionnaire (SGRQ).
次要结局
- Dyspnea(12 weeks)
- Lung function(12 weeks)
- Adverse events(12 weeks)
- Other tools for quality of life(12 weeks)