Prevention of Acute Exacerbation in Subjects With COPD by Bacterial Decolonization in Lower Respiratory Tract
Condition: Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): oral probiotics; aerosol inhaled amikacin; combined vaccination
Intervention type(s): Dietary Supplement; Drug; Biological
Intervention description(s): Culturelle™ DIGESTIVE HEALTH 30 CT(VCAP)(10 Billion Claim) which consists of 100% Lactobacillus rhamnosus GG, 1 tablet, q.d., for 3 months.
Subjects will take conventional therapy at the same time.; 0.4g Amikacin sulfate injection + 5ml saline, aerosol inhalation, b.i.d., 5-7 days per month, for 3 months.
In order to observe and cope with adverse events timely, subjects will be admitted to the ward during the course of medication.
Subjects will take conventional therapy at the same time.; Influenza Vaccine recommended by World Health Organization(WHO) in that year and imported 23-Valent Pneumococcal Polysaccharide Vaccine approved by China Food and Drug Administration(CFDA) are vaccinated at different body sites by professional nurses.
The interval between two vaccinations is 3-5 days to avoid the overlap of adverse events.
Subjects will take conventional therapy at the same time.
Intervention MeSH terms: Amikacin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are equally assigned to four groups in parallel to accept oral probiotics, aerosol inhaled amikacin, combined vaccination or blank control for the duration of the study.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: chronic obstructive pulmonary disease; aerosol inhaled amikacin; oral probiotics; combined influenza and pneumococcal vaccine inoculation; bacterial decolonization in lower respiratory tract