Santeon-CAP; Dexamethasone in Community-acquired Pneumonia

• ClinicalTrials.gov Identifier: NCT01743755
• Recruitment Status: Terminated
• First Posted: December 6, 2012
• Last Update Posted: April 18, 2019
• Sponsor: St. Antonius Hospital
• Collaborators: Canisius-Wilhelmina Hospital; Onze Lieve Vrouw Hospital; Catharina Ziekenhuis Eindhoven; Maasstad Hospital
• Information provided by (Responsible Party): Dr. WJW Bos, St. Antonius Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Community-acquired Pneumonia	Drug: Dexamethasone; Drug: Placebo	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 413 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Santeon-CAP; Dexamethasone in Community-acquired Pneumonia.
• Study Start Date: December 2012
• Actual Primary Completion Date: July 13, 2018
• Actual Study Completion Date: September 13, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Dexamethasone	Drug: Dexamethasone; Dexamethasone tablet 6 mg, once daily for four consecutive days
Placebo Comparator: Placebo; Placebo tablet, once daily for four consecutive days	Drug: Placebo; Placebo tablet, once daily for four consecutive days

Outcome Measures

Primary Outcome Measures :

1. 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. ]
   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 Outcome Measures :

1. Mortality [ Time Frame: 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.
2. 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. ]
   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 Outcome Measures:

1. Mortality [ Time Frame: Day 365 ]
   One year after admission patient's status will be recorded.
2. S. pneumoniae prevalence [ Time Frame: 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.
3. Renal damage [ Time Frame: 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.
4. Cost-effectiveness [ Time Frame: 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.
5. Post-infectious fatigue [ Time Frame: 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.
6. Pathogenesis of CAP at respiratory mucosa [ Time Frame: 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.
7. 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. ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Netherlands

Canisius Wilhelmina Hospital

Nijmegen, Gelderland, Netherlands, 6532 SZ

Catharina hospital Eindhoven

Eindhoven, Noord-Brabant, Netherlands, 5623 EJ

OLVG

Amsterdam, Noord-Holland, Netherlands, 1091 AC

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands, 3430 EM

Sponsors and Collaborators

St. Antonius Hospital

Canisius-Wilhelmina Hospital

Onze Lieve Vrouw Hospital

Catharina Ziekenhuis Eindhoven

Maasstad Hospital

Investigators

• 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 Ziekenhuis Eindhoven
• Principal Investigator: Paul Bresser, MD, PhD; Onze Lieve Vrouwen Gasthuis
• Principal Investigator: Stijn Konings, MD, PhD; Catharina Ziekenhuis Eindhoven
• Principal Investigator: Willem Blok, MD, PhD; Onze Lieve Vrouwen Gasthuis

More Information

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Dr. WJW Bos, Principal Investigator, St. Antonius Hospital
• ClinicalTrials.gov Identifier: NCT01743755
• Other Study ID Numbers: Santeon-CAP; 2011-004566-14 ( EudraCT Number )
• First Posted: December 6, 2012
• Last Update Posted: April 18, 2019
• Last Verified: April 2019

Keywords provided by Dr. WJW Bos, St. Antonius Hospital:

Community-acquired pneumonia; Dexamethasone; Corticosteroid

Additional relevant MeSH terms:

Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Dexamethasone; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents