Abstract
BackgroundCommunity-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting.Methods/DesignThis randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint.DiscussionThis largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects.Trial registration7 September 2009 on ClinicalTrials.gov: NCT00973154.
Highlights
Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide
This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization
A small-sized multicenter randomized trial showed a significant reduction in hospital mortality in severe CAP with a seven-day continuous infusion of hydrocortisone (240 mg/day), this study was not powered for mortality [10]
Summary
Even with the prescription of newer and more potent antimicrobial agents, mortality due to CAP has remained relatively constant over time. Two randomized double-blind controlled trials including 200 to 300 patients with all severities of CAP found controversial results: the first study using 40 mg of prednisolone for seven days showed no effect on time to clinical stability, with a higher rate of late failure in the corticosteroid group, defined by recurrence of signs and symptoms of pneumonia after 72 hours of admission after an initially beneficial response to treatment [12]. We decided against tapering of the glucocorticoid dose in order not to prolong glucocorticoid exposure This current large and adequately powered randomized trial will determine the risks and benefits of adding 50 mg of prednisone for 7 days to the treatment of hospitalized patients with CAP.
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