Rationale and design of CAPITA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults

The burden of community-acquired pneumonia (CAP) among the elderly is high and has increased over the last decades. Streptococcus pneumoniae is the most common cause of CAP and in 10% the infection may be fatal. Although the 23-valent polysaccharide pneumococcal vaccine (23vPS) is considered effective in the prevention of invasive pneumococcal disease in the elderly population, the evidence is mainly from nonrandomised observational studies and effects on the occurrence of pneumonia have not been demonstrated. Conjugated pneumococcal vaccines which also stimulate T-cell dependent immune responses induced antibody responses in elderly persons which are similar to those induced by a primary series of 7-valent conjugated pneumococcal vaccine (7vPnC) in infants, and the response appeared similar or superior for all vaccine serotypes to that induced by 23vPS. The primary objective of the planned trial entitled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults) is to establish the efficacy of a 13-valent PnC vaccine in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adult persons aged 65 years and older. This is a parallel group, randomised, placebo-controlled trial, with a 1:1 random allocation to vaccine or placebo vaccine. The occurrence of the primary outcome of vaccine-serotype specific (VT)-CAP will be established in hospitals on the basis of three sets of criteria: (1) a clinical definition of CAP; (2) independent interpretation of chest radiograph consistent with pneumonia: and (3) determination of S. pneumonia serotype. the trial will be critical to determine the position of conjugate pneumococcal vaccines in the prevention of pneumococcal disease.