Santeon-CAP; Dexamethasone in Community-acquired Pneumonia

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 Overview

• Status: Terminated
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Drug: Dexamethasone; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6532 SZ
      • Canisius Wilhelmina Hospital
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Catharina Hospital Eindhoven
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1091 AC
      • OLVG
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3430 EM
      • St. Antonius Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	One year after admission patient's status will be recorded.	Day 365
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)
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)
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.
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
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)
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.

Collaborators and Investigators

• Sponsor: St. Antonius Hospital
• Collaborators: Catharina Ziekenhuis Eindhoven; Onze Lieve Vrouw Hospital; Maasstad Hospital; Canisius-Wilhelmina Hospital
• Investigators: Principal Investigator: Willem Jan Bos, MD, PhD, St. Antonius Hospital; Principal Investigator: Jan Grutters, Prof, MD, St. Antonius 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

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 13, 2018
• Study Completion (Actual): September 13, 2018

Study Registration Dates

• First Submitted: November 22, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Corticosteroid; Dexamethasone; Community-acquired pneumonia
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: Santeon-CAP; 2011-004566-14 (EudraCT Number)