Prevention of Acute Exacerbation in Subjects With COPD by Bacterial Decolonization in Lower Respiratory Tract
Prevention of Acute Exacerbation in Subjects With COPD by Bacterial Decolonization in Lower Respiratory Tract
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.
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.

 Effects of these above methods on the decolonization of potential pathogenic bacteria in
 lower respiratory tract and the inflammatory reaction are not clear. 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.
Inclusion Criteria:

 1. Written informed consent must be obtained before any assessment is performed

 2. Male or female adults aged 18-65 years

 3. 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)

 4. Moderate to very severe airflow limitation (post-bronchodilator FEV1 < 80% of the
 predicted normal value)

 5. 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.

 6. In the stable stage of COPD

 Exclusion Criteria:

 1. 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

 2. Patients who are in critical conditions

 3. 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

 4. Patients with concomitant pulmonary disease (including but not limited to
 bronchiectasis, interstitial lung disease, asthma)

 5. Patients who are highly likely to be lost during the 3-month treatment and the 1-year
 follow up

 6. Pregnant or nursing (lactating) women

 7. Patients who have been vaccinated against influenza in the current year, or against
 Streptococcus pneumoniae within five years, or have vaccination contraindications

 8. Patients who are allergic to amikacin or other aminoglycosides

 9. Patients who have participated in any interventional clinical trials in the three
 months prior to screening

 10. Patients with mental diseases or cognitive disorders which could interfere with
 treatment and follow-up