Community-acquired Pneumonia
Conditions
Keywords
Community-acquired pneumonia, Dexamethasone, Corticosteroid
Brief summary
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
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).
Interventions
DRUGDexamethasone
Dexamethasone tablet 6 mg, once daily for four consecutive days
DRUGPlacebo
Placebo tablet, once daily for four consecutive days
Sponsors
Canisius-Wilhelmina Hospital
Onze Lieve Vrouw Hospital
Catharina Ziekenhuis Eindhoven
Maasstad Hospital
St. Antonius Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | day 30 | 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. |
| ICU admission | hospital admission (=day 1) until hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. | In the period the patient is admitted to the hospital, admission to the intensive care unit will be recorded (yes/no and specific date). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cost-effectiveness | Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. | To study the cost-effectiveness of dexamethasone and outcome of CAP. Resource utilization will be acquired for the entire period of hospital stay for each individual patient. |
| Post-infectious fatigue | Day 30 and day 90 | To study post-infectious fatigue that occurs in certain patients after a CAP episode. On day 1, day 4, day of discharge, and 30 and 90 days after admission, the patient will be asked to fill in the EQ-5D questionnaire. Furthermore, on day 4, 30 and 90 days after admission, the patient will be asked to fill in the RAND-36 questionnaire. |
| Mortality | Day 365 | One year after admission patient's status will be recorded. |
| Predefined subgroup analysis of length of stay | Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. | To study what patients admitted with CAP benefit most from dexamethasone therapy, based on predefined subgroup analysis with: * disease severity score (PSI 1-3 vs. PSI 4-5); * C-reactive protein level at admission; * causative microorganism (Pneumococcus urinary antigen test positive vs. negative); * cytokine response (IL-6 and IL-10) over time; * cortisol level over time; * procalcitonin over time; * vitamin D level on admission. |
| Pathogenesis of CAP at respiratory mucosa | Day of admission (=day 1) and day 30 (outpatient visit) | To study the pathogenesis of CAP at the respiratory mucosa (this will be done in two of the four study centra). At the day of hospital admission a nasopharyngeal swab will be taken to determine aetiology of the respiratory mucose. 30 days after admission (during the outpatient visit) another nasopharyngeal swab will be taken to explore changes. |
| S. pneumoniae prevalence | Hospital admission (= day 1) | To study the prevalence of different S. pneumoniae serotypes in The Netherlands (based on the serotype distribution of isolated strains as well as the increase of serotype specific antibodies). Serotyping will be performed in a bloodsample taken on the day of admission. |
| Renal damage | Admission (=day 1) and day 30 (outpatient visist) | To study acute renal damage, and its effect on outcome, in patients with CAP. A urine sample will be taken on the day of admission, on day 4 and on the outpatient visit at day 30. |
Countries
Netherlands
Outcome results
None listed