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Santeon-CAP; Dexamethasone in Community-acquired Pneumonia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by St. Antonius Hospital
Sponsor:
Collaborators:
Canisius-Wilhelmina Hospital
Onze Lieve Vrouw Hospital
Catharina Ziekenhuis Eindhoven
Information provided by (Responsible Party):
Dr. WJW Bos, St. Antonius Hospital
ClinicalTrials.gov Identifier:
NCT01743755
First received: November 22, 2012
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Community-acquired Pneumonia
Drug: Dexamethasone
Drug: Placebo
Phase 4

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by St. Antonius Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Other Outcome Measures:
  • 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.


Estimated Enrollment: 600
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)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01743755

Contacts
Contact: Simone Spoorenberg, MD s.spoorenberg@antoniusziekenhuis.nl

Locations
Netherlands
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         
OLVG Recruiting
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    s.spoorenberg@antoniusziekenhuis.nl   
Contact: Willem Jan Bos, MD    0031652741245    w.bos@antoniusziekenhuis.nl   
Sub-Investigator: Simone Spoorenberg, MD         
Principal Investigator: Willem Jan Bos, MD         
Principal Investigator: Jan Grutters, MD, prof         
Sponsors and Collaborators
St. Antonius Hospital
Canisius-Wilhelmina Hospital
Onze Lieve Vrouw Hospital
Catharina Ziekenhuis Eindhoven
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 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
  More Information

Publications:
Responsible Party: Dr. WJW Bos, Principal Investigator, St. Antonius Hospital
ClinicalTrials.gov Identifier: NCT01743755     History of Changes
Other Study ID Numbers: Santeon-CAP, 2011-004566-14
Study First Received: November 22, 2012
Last Updated: September 11, 2014
Health Authority: Netherlands: Independent Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by St. Antonius Hospital:
Community-acquired pneumonia
Dexamethasone
Corticosteroid

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014