Santeon-CAP; Dexamethasone in Community-acquired Pneumonia

Study Overview
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Brief Summary
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The present study is designed to investigate the beneficial effects of adjunctive dexamethasone therapy in patients admitted with community-acquired pneumonia, additionally aiming at assessing what patients benefit from dexamethasone treatment mostly. A large multicenter study will be conducted comparing a 4 days dexamethasone 6 mg per os course with placebo in 600 patients and with predefined subgroup analyses planned.

Detailed Description
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Community-acquired pneumonia (CAP) is a common infection. Approximately 20 percent of all episodes of pneumonia result in hospitalization. It is the leading cause of community-acquired infection requiring intensive care unit (ICU) admission. In pulmonary infections, the release of cytokines and other inflammatory mediators from alveolar macrophages serves as a mechanism by which invading pathogens are eliminated. However, this reaction of the innate immune system can be potentially harmful when excessive release of circulating inflammatory cytokines causes damage to the patient, particularly the lung. Interest in the role of corticosteroids in the pathophysiology of critical illness has existed since the early part of the 20th century. On ICU, early treatment with corticosteroids to attenuate systemic inflammation is widespread. At the same time, outside the ICU little evidence is available on the effect of treatment with corticosteroids in patients diagnosed with CAP. Theoretically, early initiated administration of corticosteroids in the course of a CAP can lower systemic and pulmonary inflammation. This may lead to earlier resolution of pneumonia and a reduction of complications (sepsis, mortality).

Official Title
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Santeon-CAP; Dexamethasone in Community-acquired Pneumonia.

Conditions
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Community-acquired Pneumonia

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Chest radiograph showing new opacities. In combination with two of the following findings: Cough Production of sputum Temp >38,0 °C or <36,0 °C Audible abnormalities by chest examination compatible with pneumonia Leukocytosis (>10.000 cells/mm3), leftward shift (>10%) or leucopenia (<4000 cells/mm3) C-reactive protein > 15 mg/l (three fold higher than the upper limit of normal) Exclusion Criteria: Immunocompromised patients: Patients with a known congenital or acquired immunodeficiency. Patients who received chemotherapy less than 6 weeks ago. Patients who received corticosteroids in the last 6 weeks. Patients who received immunosuppressive medication in the last 6 weeks (e.g. cyclosporin, cyclophosphamide, azathioprine). Patients with chronic obstructive pulmonary disease who are on systemic corticosteroids. Patients who require intensive care unit treatment. Patients with tropical worm infection. Patients with dexamethasone intolerance. Pregnant and breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexamethasone<br> | Drug: Dexamethasone<br>* Dexamethasone tablet 6 mg, once daily for four consecutive days<br>|
| Placebo Comparator: Placebo<br>Placebo tablet, once daily for four consecutive days | Drug: Placebo<br>* Placebo tablet, once daily for four consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Discharge date will be the date on which the patient is clinically ready to be discharged (which means days of hospital stay on basis of social indication will be excluded from analyses). Median length of stay in an earlier CAP study performed in the St. Antonius Hospital in Nieuwegein was 6.5 days, thus patients will be followed during an expected average of 1 week. | Hospital admission (= day 1 = timepoint at which patient presents in hospital) until hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 30 days after hospital admission (=day 1) the patient will visit the hospital for a out-patient visit. At that time, patient's status will be recorded. | day 30 | 
| ICU admission | In the period the patient is admitted to the hospital, admission to the intensive care unit will be recorded (yes/no and specific date). | hospital admission (=day 1) until hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Community-acquired pneumonia, Dexamethasone, Corticosteroid