Clinical trial NCT01743755: Santeon-CAP; Dexamethasone in Community-acquired Pneumonia
Official title: Santeon-CAP; Dexamethasone in Community-acquired Pneumonia.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Community-acquired Pneumonia
Keywords: Community-acquired pneumonia
Dexamethasone
Corticosteroid
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: Canisius-Wilhelmina Hospital
name: Onze Lieve Vrouw Hospital
name: Catharina Ziekenhuis Eindhoven
name: Maasstad Hospital
First posted: 2012-12-06
Enrollment: 413
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Length of hospital stay
timeFrame: 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 outcomes:
measure: Mortality
timeFrame: day 30
measure: ICU admission
timeFrame: hospital admission (=day 1) until hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week.
Other outcomes:
measure: Mortality
timeFrame: Day 365
measure: S. pneumoniae prevalence
timeFrame: Hospital admission (= day 1)
measure: Renal damage
timeFrame: Admission (=day 1) and day 30 (outpatient visist)
measure: Cost-effectiveness
timeFrame: Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week.
measure: Post-infectious fatigue
timeFrame: Day 30 and day 90
measure: Pathogenesis of CAP at respiratory mucosa
timeFrame: Day of admission (=day 1) and day 30 (outpatient visit)
measure: Predefined subgroup analysis of length of stay
timeFrame: Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week.
Locations:
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
state: Gelderland
city: Eindhoven
country: Netherlands
facility: Catharina hospital Eindhoven
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: OLVG
state: Noord-Holland
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
Study officials:
affiliation: St. Antonius Hospital
name: Willem Jan Bos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Antonius Hospital
name: Jan Grutters, Prof, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Canisius-Wilhelmina Hospital
name: Rob Janssen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Catharina Ziekenhuis Eindhoven
name: Frank Smeenk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Onze Lieve Vrouwen Gasthuis
name: Paul Bresser, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Catharina Ziekenhuis Eindhoven
name: Stijn Konings, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Onze Lieve Vrouwen Gasthuis
name: Willem Blok, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meijvis SC, Hardeman H, Remmelts HH, Heijligenberg R, Rijkers GT, van Velzen-Blad H, Voorn GP, van de Garde EM, Endeman H, Grutters JC, Bos WJ, Biesma DH. Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jun 11;377(9782):2023-30. doi: 10.1016/S0140-6736(11)60607-7. Epub 2011 Jun 1.
citation: Wittermans E, Vestjens SMT, Spoorenberg SMC, Blok WL, Grutters JC, Janssen R, Rijkers GT, Smeenk FWJM, Voorn GP, van de Garde EMW, Bos WJW; Santeon-CAP Study Group; Members of the Santeon-CAP Study Group. Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial. Eur Respir J. 2021 Aug 12;58(2):2002535. doi: 10.1183/13993003.02535-2020. Print 2021 Aug.
citation: Vestjens SMT, Wittermans E, Spoorenberg SMC, Grutters JC, van Ruitenbeek CA, Voorn GP, Bos WJW, van de Garde EMW. Inter-hospital variation in the utilization of diagnostics and their proportionality in the management of adult community-acquired pneumonia. Pneumonia (Nathan). 2018 Dec 25;10:15. doi: 10.1186/s41479-018-0059-0. eCollection 2018.