ArticlesAdjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial
Introduction
Respiratory tract infections and pneumonia in particular are the third-leading cause of death worldwide.1 Although outcome of community-acquired pneumonia improved with the availability of antibiotics, this disorder still carries a high risk for long-term morbidity and mortality.2 Adjunct therapeutic interventions could improve outcome of patients with this type of pneumonia.
In community-acquired pneumonia, an excessive release of circulating inflammatory cytokines can be harmful and cause pulmonary dysfunction. Systemic corticosteroids have anti-inflammatory effects, attenuating the systemic inflammatory process in the disorder.3 Therefore, adjunct treatment with corticosteroids has been discussed since the 1950s, when favourable effects of corticosteroids were noted in pneumococcal pneumonia.4 More recently, a significant reduction of in-hospital mortality in patients with severe community-acquired pneumonia was noted in a small randomised trial5 (n=46) testing a 7-day continuous infusion of hydrocortisone versus placebo. A retrospective single-centre study6 including 308 patients suggested that the use of corticosteroids was associated with decreased mortality. Two recent randomised placebo-controlled trials7, 8 including 200–300 patients revealed controversial results. Whereas the first trial7 did not find any benefit of adjunct prednisolone, but an increased recurrence rate, the second trial8 in which patients received intravenous dexamethasone over 4 days reported a significant reduction in length of hospital stay by 1 day. Two systematic reviews9, 10 and three meta-analyses11, 12, 13 concluded that adjunct corticosteroids in community-acquired pneumonia might be beneficial, but a large, adequately powered randomised trial is warranted.
Therefore, we investigated the effects of short-term prednisone versus placebo in patients admitted to hospital for community-acquired pneumonia with the primary endpoint of time to clinical stability.
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Study design and participants
This is an investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial. Details of the trial design have previously been published.14 In brief, consecutive patients presenting with community-acquired pneumonia were screened and enrolled at emergency departments or medical wards in seven tertiary care hospitals in Switzerland from Dec 1, 2009, to May 21, 2014, within 24 h of presentation. Inclusion criteria were age 18 years or older and hospital admission with
Results
We enrolled 802 eligible patients in the trial and randomly assigned them to receive either prednisone or placebo (figure 1). After blinded post-randomisation exclusion of 17 patients retrospectively not meeting eligibility criteria, 392 patients were allocated to the prednisone group and 393 patients to the placebo group.
Baseline characteristics of the two groups were well balanced (table 1). Median age of patients was 74 years, and 487 (62%) of 785 were men. Patients had a high burden of
Discussion
In this trial, a 7-day treatment with prednisone in patients with community-acquired pneumonia led to a reduction in time to clinical stability of 1·4 days, to an overall reduction of length of hospital stay of 1 day, and to a reduction in duration of intravenous antibiotic treatment of 1 day. This effect seemed to be valid across all PSI classes and independent of age. Incidence of pneumonia-associated complications until day 30 tended to be lower in the prednisone group than in the placebo
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These authors contributed equally to this work