Elsevier

The Lancet

Volume 351, Issue 9100, 7 February 1998, Pages 399-403
The Lancet

Articles
Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people

https://doi.org/10.1016/S0140-6736(97)07358-3Get rights and content

Summary

Background

We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised-middle-aged and elderly people.

Methods

The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50–85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group.

Findings

63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0·83 (95% CI 0·58–1·12, p=0·31). Pneumococcal pneumonia was diagnosed in 16 (4·5%) patients in the placebo group and in 19 (5·6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0·78 (95% CI 0·40–1·51, p=0·45). We found no difference in the death rate between the two study groups.

Interpretation

The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals.

Introduction

Polyvalent pneumococcal capsular polysaccharide vaccine is effective in the prevention of invasive pneumococcal disease in immunocompetent people,1, 2, 3, 4 and of pneumococcal pneumonia in healthy young men.5, 6 However, the vaccine's protective efficacy against pneumococcal pneumonia in middle-aged and elderly people remains unknown. Most randomised controlled studies have shown no benefit from vaccination among older, high-risk adults7, 8, 9 possibly because there were too few participants or the estimated frequency of pneumococcal pneumonia in the study populations was too high.10

About 10 years ago, Clemens and Shapiro11 argued that randomised clinical trials were unlikely to resolve the question of the vaccine's efficacy. Although a randomised trial is a powerful method, ethical objections to random allocation of a licensed and potentially life-saving vaccine, and the enormous sample size required, called for studies that were observational and, in particular, case-controlled.

In Sweden, no recommendation concerning the use of the pneumococcal vaccine existed until the end of 1994, and because the earlier use had been very limited (roughly 1500 doses per year in a population of nearly 9 million) no ethical objections to randomised clinical trials were raised before that time. One way to reduce the sample size needed is to study a population at high risk of pneumonia. Patients treated in hospital, for any cause, have a high probability of readmission with pneumonia within 5 years.12 In patients admitted to hospital with a diagnosis of pneumonia, the risk of readmission with the same diagnosis is even higher.13

We therefore undertook a prospective, multicentre, double-blind, randomised, placebo-controlled trial of the 23-valent pneumococcal vaccine in middle-aged and elderly patients without known immunosuppression, who had been discharged from hospital after treatment for pneumonia. Our primary objective was to assess the effectiveness of the pneumococcal vaccine in the prevention of pneumococcal pneumonia and pneumonia overall.

Section snippets

Study design

Patients who had been treated in hospital for community-acquired pneumonia (CAP) were randomly assigned in equal proportions to receive 23-valent pneumococcal capsular polysaccharide vaccine (Pneumovax, MSD, NJ, USA) 0·5 mL (25 μg each capsular type) or placebo (sodium chloride) 0·5 mL intramuscularly, in a double-blind, multicentre study. Patients on anticoagulant treatment received the vaccine subcutaneously.

Randomisation was done by the vaccine manufacturer (MSD) and the code was not

Definitions

Primary and secondary endpoints—Primary endpoints were pneumonia, defined as acute clinical symptoms or signs compatible with a lower-respiratory-tract infection and a new infiltrate on chest radiography; and pneumococcal pneumonia, defined as pneumonia and a positive culture from blood, pleural fluid, or sputum (≥105 colony-forming units per mL in a purulent sample) or a positive pneumococcal antibody test. Secondary endpoints were bacteraemic pneumococcal pneumonia and death from all causes.

Results

Consecutive eligible patients treated for CAP between January, 1991, and January, 1994, were reviewed for inclusion. Of 1549 reviewed, 894 (58%) patients were excluded (figure 1). “Presumed poor compliance” included patients who were unable, for practical reasons (eg, distance, transport difficulties), to contact the hospital in case of a suspected recurrent pneumonia (191 patients); patients with mental impairment or severe chronic alcoholism (187 patients); and patients bed-ridden owing to a

Discussion

We found the polyvalent pneumococcal polysaccharide vaccine to be safe, with no serious adverse events. This finding is consistent with previous research.22 We were unable to show that the vaccine was effective in the prevention of pneumonia overall or of pneumococcal pneumonia, despite a high incidence of these diseases in the study population. Nor could we find any difference in death rates between the study groups. However, a higher (though not significant) rate of bacteraemia occurred in

References (30)

  • R Austrian et al.

    Prevention of pneumococcal pneumonia by vaccination

    Trans Assoc Am Physicians

    (1976)
  • P Smit et al.

    Protective efficacy of pneumococcal polysaccharide vaccines

    JAMA

    (1977)
  • MS Simberkoff et al.

    Efficacy of pneumococcal vaccine in high-risk patients

    N Engl J Med

    (1986)
  • JA Leech et al.

    Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease

    Can Med Assoc J

    (1987)
  • DS Fedson et al.

    Pneumococcal vaccine after 15 years of use

    Arch Intern Med

    (1994)
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