Santeon-CAP; Dexamethasone in Community-acquired Pneumonia

Community-acquired Pneumonia Clinical Trial

Official title:

Santeon-CAP; Dexamethasone in Community-acquired Pneumonia.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01743755
• Other study ID #: Santeon-CAP
• Secondary ID: 2011-004566-14
• Status: Terminated
• Phase: Phase 4
• Start date: December 2012
• Est. completion date: September 13, 2018

Study information

• Verified date: April 2019
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 413
• Est. completion date: September 13, 2018
• Est. primary completion date: July 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Pneumonia

Intervention

Drug:
• Dexamethasone
Dexamethasone tablet 6 mg, once daily for four consecutive days
• Placebo
Placebo tablet, once daily for four consecutive days

Locations

Country	Name	City	State
Netherlands	OLVG	Amsterdam	Noord-Holland
Netherlands	Catharina hospital Eindhoven	Eindhoven	Noord-Brabant
Netherlands	St. Antonius Hospital	Nieuwegein	Utrecht
Netherlands	Canisius Wilhelmina Hospital	Nijmegen	Gelderland

Sponsors (5)

Lead Sponsor	Collaborator
St. Antonius Hospital	Canisius-Wilhelmina Hospital, Catharina Ziekenhuis Eindhoven, Maasstad Hospital, Onze Lieve Vrouw Hospital

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	One year after admission patient's status will be recorded.	Day 365
Other	S. pneumoniae prevalence	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.	Hospital admission (= day 1)
Other	Renal damage	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.	Admission (=day 1) and day 30 (outpatient visist)
Other	Cost-effectiveness	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.	Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week.
Other	Post-infectious fatigue	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.	Day 30 and day 90
Other	Pathogenesis of CAP at respiratory mucosa	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.	Day of admission (=day 1) and day 30 (outpatient visit)
Other	Predefined subgroup analysis of length of stay	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.	Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week.
Primary	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	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
Secondary	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.