PPSV23 Pneumococcal Vaccine in Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

Summary: 
      Streptococcus pneumoniae is the most common causes of community-acquired pneumonia and
      exacerbations in chronic obstructive pulmonary disease (COPD) patients, which are associated
      with morbidity, mortality, and higher health-care cost. In addition, recently high daily dose
      of inhaled corticosteroid (ICS) therapy became more evident to be beneficial in
      moderate-to-severe COPD patients, but excess risk of pneumonia shown in database analysis was
      worried about by primary physicians. The use of pneumococcal polysaccharide vaccination
      (PPSV23) has protective efficacy to eliminate infection of Streptococcus pneumoniae from
      previous studies. If the use of PPSV23 can reduce the incidence of pneumonia or exacerbations
      in COPD patients using high daily dose of ICS, the benefit of ICS can be preserved and risk
      of pneumonia can be reduced. However, there is only limited data supporting this hypothesis.
      In this study, the investigators will conduct a double-blinded, randomized controlled trial
      to evaluate the clinical efficacy of PPSV23 in severe COPD patients using high daily dose of
      ICS.
    

Detailed description: 
      Exacerbations are a common feature in moderate-to-severe chronic obstructive pulmonary
      disease (COPD). Morbidity, mortality and health-care costs of these patients largely result
      from exacerbations. The most common causes of an exacerbation are infection of
      tracheobronchial tree. Among them, Streptococcus pneumoniae is the most frequently isolated
      organism, accounting for 5-25% patients of COPD, while it is also the most commonly
      identified cause in community-acquired pneumonia (CAP), accounting for 16.5-38.9% of CAP
      patients.

      In recent years, widespread emergence of antimicrobial resistance in Streptococcus pneumoniae
      has became a major global concern, especially in Taiwan, one of the highest levels of
      antibiotic-resistant pneumococci in the world. Therefore, primary prevention by vaccination
      is encouraged for those high-risk patients with COPD. The currently available adult
      pneumococcal vaccine consists of the capsular polysaccharide of 23 different serotypes of
      Streptococcus pneumoniae (PPSV23). The antibodies produced in response to this polysaccharide
      can provide protection by inducing host immune cells to kill or to opsonize bacteria for
      phagocytosis.

      Until now, few studies have been designed to specifically examine vaccine efficacy in COPD
      patients. Among 3 available randomized controlled trials, only one study involving 596
      patients found, from post-hoc analyses, some protective efficacy for pneumonia in patients of
      < 65 years of age and of an FEV1 < 40% predicted. Based on above evidence (only limited body
      of data), the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 Guideline
      has recommended the PPSV23 inoculation as evidence B.

      By the way, in comparison to placebo and the single components, a superior control by means
      of the inhaled corticosteroids (ICS)/long-acting beta2-agonist (LABA) fixed combination
      therapy has been demonstrated for significant clinical improvement in moderate-to-severe COPD
      patients, except mortality, by meta-analysis and large prospective studies (TORCH [Towards a
      Revolution in COPD Health] trial and INSPIRE [Investigating New Standards for Prophylaxis in
      Reduction of Exacerbations] trial). However, those database indicated that high daily dose of
      ICS (fluticasone propionate at a dose of 500-1000mcg daily) was associated with an excess
      risk of pneumonia, which doubles the pneumonia incidence in patients not receiving ICS. The
      immunogenicity of PPSV23 in COPD patients using systemic steroid was demonstrated but the
      clinical efficacy of vaccination has not been investigated.

      From above-mentioned background, if the use of PPSV23 can reduce the incidence of pneumonia
      or exacerbations in COPD patients using high daily dose of ICS, the benefit of ICS can be
      preserved and risk of pneumonia can be reduced. For primary physicians, this hypothesis, if
      true, is very beneficial. So, in this study, the investigators want to conduct a
      double-blinded, randomized controlled trial to evaluate the clinical efficacy of PPSV23 in
      COPD patients using high daily dose of ICS.
    

Intervention name(s): PPSV23 pneumococcal vaccine (Pneumovax®); Normal Saline
Intervention type(s): Biological; Drug
Intervention description(s): The adult anti-pneumococcal vaccine was a 23-polyvalent pneumococcal vaccine (Pneumovax®, Aventis Pastuer MSD), 0.5 ml of which was given subcutaneously. Duration of the efficacy is about 4-5 years.; normal saline, 0.5ml given subcutaneously
Other intervention name(s): Pneumovax®, Aventis Pastuer MSD
Intervention MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Chronic obstructive pulmonary disease; Inhaled corticosteroid; Pneumococcal vaccine; Acute exacerbation; High-dose daily inhaled corticosteroid usage; Efficacy of the PPSV23 pneumococcal vaccine