Santeon-CAP; Dexamethasone in Community-acquired Pneumonia
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Santeon-CAP; Dexamethasone in Community-acquired Pneumonia.|
- Length of hospital stay [ Time Frame: 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. ] [ Designated as safety issue: No ]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.
- Mortality [ Time Frame: day 30 ] [ Designated as safety issue: Yes ]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 [ Time Frame: hospital admission (=day 1) until hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. ] [ Designated as safety issue: Yes ]In the period the patient is admitted to the hospital, admission to the intensive care unit will be recorded (yes/no and specific date).
- Mortality [ Time Frame: Day 365 ] [ Designated as safety issue: No ]One year after admission patient's status will be recorded.
- S. pneumoniae prevalence [ Time Frame: Hospital admission (= day 1) ] [ Designated as safety issue: No ]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 [ Time Frame: Admission (=day 1) and day 30 (outpatient visist) ] [ Designated as safety issue: No ]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.
- Cost-effectiveness [ Time Frame: Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. ] [ Designated as safety issue: No ]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 [ Time Frame: Day 30 and day 90 ] [ Designated as safety issue: No ]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.
- Pathogenesis of CAP at respiratory mucosa [ Time Frame: Day of admission (=day 1) and day 30 (outpatient visit) ] [ Designated as safety issue: No ]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.
- Predefined subgroup analysis of length of stay [ Time Frame: Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week. ] [ Designated as safety issue: No ]
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.
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Dexamethasone||
Dexamethasone tablet 6 mg, once daily for four consecutive days
Placebo Comparator: Placebo
Placebo tablet, once daily for four consecutive days
Placebo tablet, once daily for four consecutive days
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01743755
|Contact: Simone Spoorenberg, MDfirstname.lastname@example.org|
|Canisius Wilhelmina Hospital||Recruiting|
|Nijmegen, Gelderland, Netherlands, 6532 SZ|
|Contact: Rob Janssen, MD|
|Principal Investigator: Rob Janssen, MD|
|Sub-Investigator: Hester Zeegers, MD|
|Principal Investigator: Tom Sprong, MD|
|Catharina hospital Eindhoven||Recruiting|
|Eindhoven, Noord-Brabant, Netherlands, 5623 EJ|
|Contact: Frank Smeenk, MD|
|Principal Investigator: Frank Smeenk, MD|
|Principal Investigator: Stijn Konings, MD|
|Amsterdam, Noord-Holland, Netherlands, 1091 AC|
|Contact: Paul Bresser, MD|
|Principal Investigator: Paul Bresser, MD|
|Principal Investigator: Willem Blok, MD|
|St. Antonius Hospital||Recruiting|
|Nieuwegein, Utrecht, Netherlands, 3430 EM|
|Contact: Simone Spoorenberg, MD 0031628060284 email@example.com|
|Contact: Willem Jan Bos, MD 0031652741245 firstname.lastname@example.org|
|Sub-Investigator: Simone Spoorenberg, MD|
|Principal Investigator: Willem Jan Bos, MD|
|Principal Investigator: Jan Grutters, MD, prof|
|Principal Investigator:||Willem Jan Bos, MD, PhD||St. Antonius Hospital|
|Principal Investigator:||Jan Grutters, Prof, MD||St. Antonius Hospital|
|Principal Investigator:||Rob Janssen, MD, PhD||Canisius-Wilhelmina Hospital|
|Principal Investigator:||Frank Smeenk, MD, PhD||Catharina Hospital Eindhoven|
|Principal Investigator:||Paul Bresser, MD, PhD||Onze Lieve Vrouwen Gasthuis|
|Principal Investigator:||Stijn Konings, MD, PhD||Catharina Hospital Eindhoven|
|Principal Investigator:||Willem Blok, MD, PhD||Onze Lieve Vrouwen Gasthuis|