A Randomized, Parallel, Controlled, Exploratory Study: the Efficacy and Safety of Taking Probiotics, Inhaled Antibiotics or Combined Vaccination to Prevent Acute Exacerbation in Subjects With Moderate to Severe COPD and Decolonize Bacteria in Lower Respiratory Tract.
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 144
- 试验地点
- 3
- 主要终点
- Time to the first COPD exacerbation
研究概览
简要总结
The colonization of potential pathogenic bacteria in lower respiratory tract is thought to be accountable for acute exacerbation in subjects with moderate to severe COPD. However, there is no accepted therapy for patients with COPD to remove the colonized bacteria in lower respiratory tract. Therefore, we plan to perform a multi-center, randomized, controlled trial to study the efficacy and safety of oral probiotics, aerosol inhaled amikacin or combined vaccination to decolonize bacteria in lower respiratory tract and prevent acute exacerbation of COPD.
详细描述
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incomplete reversible airflow limitation, small airway obstruction and alveolar structural damage. About 3 million patients die from COPD every year around the world. The prevalence of COPD in Chinese people over the age of 40 is as high as 12 % and has risen by 50 % in the past nine years.
Acute exacerbation is the leading cause of death in patients with COPD , and accounts for a majority of expenditure of COPD management. The colonization of potential pathogenic bacteria in the lower respiratory tract is an important cause of the acute exacerbation especially in patients with moderate and severe COPD.
Some clinical studies show that aerosol inhaled antibiotics is promising in reducing acute exacerbation, but these exploratory studies have some defects so that they can't back up for the clinical application of aerosol inhaled antibiotics. Amikacin, a kind of aminoglycosides, is sensitive to the common pathogens of acute exacerbation of COPD in China. Therefore it is necessary to carry out a clinical trial to verify its efficacy and safety in pathogen decolonization and prevention of acute exacerbation.
In addition, owing to bacterial resistance and insufficient antibiotics concentration in lower respiratory tract, developing new antibacterial materials is necessary. Oral probiotics is an another way to regulate the bacterial load and inflammatory response in lower respiratory tract, which has been proven to effectively prevent acute exacerbation in cystic fibrosis and childhood asthma. Likewise, airway bacterial burden and inflammation are two main mechanisms of acute exacerbation in COPD. Hence, considering its convenience and safety of oral probiotics, we perform a trial to make clinical evaluation for it.
What's more, influenza and streptococcus pneumoniae vaccines are separately recommended for patients with COPD in the Global Initiative for Chronic Obstructive Pulmonary Disease(GOLD), but there have been no studies on the effects of combined vaccination on bacterial decolonization in lower respiratory tract or on the prevention of acute exacerbation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
盲法说明
Although this study is unblinded, we will adopt method of allocation concealment to reduce selection bias.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed
- •Male or female adults aged 18-65 years
- •Diagnosed with COPD according to GOLD 2016 (The ratio of post-bronchodilator forced expiratory volume in 1 second (FEV1) to force vital capacity (FVC)<0.70 with the use of salbutamol 400ug)
- •Moderate to very severe airflow limitation (post-bronchodilator FEV1 < 80% of the predicted normal value)
- •A documented history of at least 2 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticoids and/or antibiotics, or at least 1 exacerbation in the previous 12 months that requires hospitalization.
- •In the stable stage of COPD
排除标准
- •Patients who have clinically significant and chronic hepatic, renal, cardiovascular and gastrointestinal abnormalities or malignant tumor (except for lung cancer) which could interfere with the assessment of the efficacy and safety of the study treatment
- •Patients who are in critical conditions
- •Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids or an acute exacerbation of any other diseases in the 4 weeks prior to screening
- •Patients with concomitant pulmonary disease (including but not limited to bronchiectasis, interstitial lung disease, asthma)
- •Patients who are highly likely to be lost during the 3-month treatment and the 1-year follow up
- •Pregnant or nursing (lactating) women
- •Patients who have been vaccinated against influenza in the current year, or against Streptococcus pneumoniae within five years, or have vaccination contraindications
- •Patients who are allergic to amikacin or other aminoglycosides
- •Patients who have participated in any interventional clinical trials in the three months prior to screening
- •Patients with mental diseases or cognitive disorders which could interfere with treatment and follow-up
研究组 & 干预措施
oral probiotics
干预措施: oral probiotics (Dietary Supplement)
aerosol inhaled amikacin
干预措施: aerosol inhaled amikacin (Drug)
combined vaccination
干预措施: combined vaccination (Biological)
结局指标
主要结局
Time to the first COPD exacerbation
时间窗: 15 months
COPD exacerbation refers to deterioration of patients' daily symptoms requiring treatment with antibiotics or systemic glucocorticoid therapy. First COPD exacerbations starting between first dose and one day after last follow-up are included.
次要结局
- modified Medical Research Council(mMRC) scale(Baseline, 3 months, 6 months, 9 months, 12 months, 15 months)
- serum C-reactive protein(CRP) levels(Baseline, 3 months)
- interleukin(IL)-6 in induced sputum(Baseline, 3 months)
- IL-1β in induced sputum(Baseline, 3 months)
- Number of Patients With Adverse Events, Serious Adverse Events, and Death(Baseline, 3 months, 6 months, 9 months, 12 months, 15 months)
- Colonization of potential pathogenic bacteria in induced sputum(Baseline, 3 months)
- Microbiome in induced sputum(Baseline, 3 months)
- Forced Expiratory Volume in 1 Second(Baseline, 3 months, 15 months)
- COPD Assessment Test(CAT) Score(Baseline, 3 months, 6 months, 9 months, 12 months, 15 months)
- IL-8 in induced sputum(Baseline, 3 months)