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Corticosteroid treatment for Community-Acquired Pneumonia - A randomized, double-blind study- The STEP trial

English title Corticosteroid treatment for Community-Acquired Pneumonia - A randomized, double-blind study- The STEP trial
Applicant Christ-Crain Mirjam
Number 150757
Funding scheme SNSF Professorships
Research institution Abteilung Endokrinologie Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Clinical Endocrinology
Start/End 01.02.2014 - 31.01.2016
Approved amount 415'302.00
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All Disciplines (2)

Discipline
Clinical Endocrinology
Internal Medicine

Keywords (7)

stress hormones; risk assessment; adrenal insufficiency; respiratory tract infections; community-acquired pneumonia; prognosis; Corticosteroids

Lay Summary (German)

Lead
Kortikosteroide für die Behandlung von Lungenentzündungen - die STEP Studie
Lay summary

Hintergrund: Die Mortalität einer Lungenentzündung hat sichseit Jahrzehnten nicht verbessert trotz der Verfügbarkeit von breitenAntibiotikatherapien. Dies lässt vermuten dass andere Faktoren für dasschlechte Outcome verantwortlich sind.

Glukokortikoide (Kortisonpräparate) werden alsentzündungshemmende Medikamente eingesetzt. Seit vielen Jahren gibt esStudien, die gezeigt haben, dass eine Therapie mit Glukokortikoiden einenNutzen bringt bei Patienten mit einer Lungenentzündung. Allerdings warendiese Studien klein, und es konnte keine definitive Schlussfolgerungüber den Nutzen einer solchen Therapie gezogen werden. Bis heute gehörtdeshalb eine Therapie mit Glukokortikoiden nicht zur Standardtherapie einerLungenentzündung.

Ziel ist es, in einer grossangelegten Studie mit 800 Patienten in mehreren Spitälern der Schweiz herauszufinden,ob eine Therapie mit Glukokortikoiden die Heilung bei einer Lungenentzündungbeschleunigen kann.

Eingeschlossen in die Studie werden Patienten mit einer Lungenentzündung, die mindestens 18 Jahre alt sind undkeine Ausschlusskriterien (wie Immunsuppression, gastrointestinale Blutung oderPrednisontherapie) aufweisen. Die Patienten erhalten entweder ein Kortikosteroid (Prednison) oder einPlacebopräparat (ein sogenanntes „Scheinmedikament“) für 7 Tage. Alle12 Stunden wird ein Studienarzt Körpertemperatur, Puls, Blutdruck, undSauerstoffsättigung messen und überprüfen ob der Patient klinischstabil ist. Nach 30 und 180 Tagen erfolgt ein Telefoninterview umsicherzustellen, dass es dem Patient gut geht, kein Rückfall erfolgte und dieTherapie gut toleriert wurde.

Unsere Hypothese ist, dass eine Therapie mit Glukokortikoiden die Zeit bis zur Heilung und klinischen Stabilitätbeschleunigt, ohne dass relevante Nebenwirkungen der Kortikosteroide auftreten.

Diese grosse multizentrische Studie wird mehrKlarheit schaffen, ob eine Therapie mit Kortikosteroiden beieiner Lungenentzündung eingesetzt werden sollte, und welche Patienten ammeisten davon profitieren können.  

 

Direct link to Lay Summary Last update: 14.08.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic patients.
Popovic Milica, Blum Claudine A, Nigro Nicole, Mueller Beat, Schuetz Philipp, Christ-Crain Mirjam (2016), Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic patients., in Diabetologia, 1-9.
Pathogen- and antibiotic-specific effects of prednisone in community-acquired pneumonia.
Wirz Sebastian A, Blum Claudine A, Schuetz Philipp, Albrich Werner C, Noppen Christoph, Mueller Beat, Christ-Crain Mirjam, Tarr Philip E, Tarr Philip E (2016), Pathogen- and antibiotic-specific effects of prednisone in community-acquired pneumonia., in The European respiratory journal, ---.
Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial
Blum Claudine Angela, Nigro Nicole, Briel Matthias, Schuetz Philipp, Ullmer Elke, Suter-Widmer Isabelle, Winzeler Bettina, Bingisser Roland, Elsaesser Hanno, Drozdov Daniel, Arici Birsen, Urwyler Sandrine Andrea, Refardt Julie, Tarr Philip, Wirz Sebastian, Thomann Robert, Baumgartner Christine, Duplain Herve, Burki Dieter, Zimmerli Werner, Rodondi Nicolas, Mueller Beat, Christ-Crain Mirjam (2015), Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial, in LANCET, 385(9977), 1511-1518.
Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial.
Blum Claudine Angela, Nigro Nicole, Briel Matthias, Schuetz Philipp, Ullmer Elke, Suter-Widmer Isabelle, Winzeler Bettina, Bingisser Roland, Elsaesser Hanno, Drozdov Daniel, Arici Birsen, Urwyler Sandrine Andrea, Refardt Julie, Tarr Philip, Wirz Sebastian, Thomann Robert, Baumgartner Christine, Duplain Hervé, Burki Dieter, Zimmerli Werner, Rodondi Nicolas, Mueller Beat, Christ-Crain Mirjam (2015), Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial., in Lancet (London, England), 385(9977), 1511-8.
Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study
Alan M., Grolimund E., Kutz A., Christ-Crain M., Thomann R., Falconnier C., Hoess C., Henzen C., Zimmerli W., Mueller B., Schuetz P. (2015), Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study, in JOURNAL OF INTERNAL MEDICINE, 278(2), 174-184.
Copeptin as a stress marker prior and after a written examination - the CoEXAM study
Urwyler Sandrine A., Schuetz Philipp, Sailer Clara, Christ-Crain Mirjam (2015), Copeptin as a stress marker prior and after a written examination - the CoEXAM study, in STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, 18(1), 134-137.
Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study
Timper Katharina, Fenske Wiebke, Kuhn Felix, Frech Nica, Arici Birsen, Rutishauser Jonas, Kopp Peter, Allolio Bruno, Stettler Christoph, Mueller Beat, Katan Mira, Christ-Crain Mirjam (2015), Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study, in JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 100(6), 2268-2274.
Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective
Schuetz Philipp, Balk Robert, Briel Matthias, Kutz Alexander, Christ-Crain Mirjam, Stolz Daiana, Bouadma Lila, Wolff Michel, Kristoffersen Kristina B., Wei Long, Burkhardt Olaf, Welte Tobias, Schroeder Stefan, Nobre Vandack, Tamm Michael, Bhatnagar Neera, Bucher Heiner C., Luyt Charles-Edouard, Chastre Jean, Tubach Florence, Mueller Beat, Lacey Michael J., Ohsfeldt Robert L., Scheibling Cara M., Schneider John E. (2015), Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective, in CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 53(4), 583-592.
Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type
Grolimund Eva, Kutz Alexander, Marlowe Robert J., Voegeli Alaadin, Alan Murat, Christ-Crain Mirjam, Thomann Robert, Falconnier Claudine, Hoess Claus, Henzen Christoph, Zimmerli Werner, Mueller Beat, Schuetz Philipp (2015), Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type, in COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 12(3), 295-305.
Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia
Nigro N., Winzeler B., Suter-Widmer I., Schuetz P., Arici B., Bally M., Blum C. A., Nickel C. H., Bingisser R., Bock A., Savoca K. Rentsch, Huber A., Mueller B., Christ-Crain M. (2015), Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia, in JOURNAL OF INTERNAL MEDICINE, 278(1), 29-37.
Mid-regional pro-atrial natriuretic peptide as independent outcome and aetiological ischemic stroke biomarker: Results from the CORISK Study
De Marchis G. M. D. M. Gian Marco, Schneider J., Weck A. W. Anja, Fluri F. F. Felix, Foerch C. F. Christian, Schuetz P. S. Philipp, Buhl D. B. Daniela, Seiler M. S. Marleen, Morgenthaler N. M. Nils, Mattle H. P. M. Heinrich P., Mueller B. M. Beat, Christ-Crain M. C. C. Mirjam, Arnold M. A. Marcel, Katan M. K. Mira (2015), Mid-regional pro-atrial natriuretic peptide as independent outcome and aetiological ischemic stroke biomarker: Results from the CORISK Study, in INTERNATIONAL JOURNAL OF STROKE, 10, 51-52.
Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery
Winzeler Bettina, Zweifel Christian, Nigro Nicole, Arici Birsen, Bally Martina, Schuetz Philipp, Blum Claudine Angela, Kelly Christopher, Berkmann Sven, Huber Andreas, Gentili Fred, Zadeh Gelareh, Landolt Hans, Mariani Luigi, Muller Beat, Christ-Crain Mirjam (2015), Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery, in JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 100(6), 2275-2282.
Prognostic value of procalcitonin in respiratory tract infections across clinical settings
Kutz Alexander, Briel Matthias, Christ-Crain Mirjam, Stolz Daiana, Bouadma Lila, Wolff Michel, Kristoffersen Kristina B., Wei Long, Burkhardt Olaf, Welte Tobias, Schroeder Stefan, Nobre Vandack, Tamm Michael, Bhatnagar Neera, Bucher Heiner C., Luyt Charles-Edouard, Chastre Jean, Tubach Florence, Mueller Beat, Schuetz Philipp (2015), Prognostic value of procalcitonin in respiratory tract infections across clinical settings, in CRITICAL CARE, 19, 74.
Symptoms and Characteristics of Individuals with Profound Hyponatremia: A Prospective Multicenter Observational Study
Nigro Nicole, Winzeler Bettina, Suter-Widmer Isabelle, Schuetz Philipp, Arici Birsen, Bally Martina, Blum Claudine, Bingisser Roland, Bock Andreas, Huber Andreas, Mueller Beat, Nickel Christian H., Christ-Crain Mirjam (2015), Symptoms and Characteristics of Individuals with Profound Hyponatremia: A Prospective Multicenter Observational Study, in JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 63(3), 470-475.
Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia
Zhydkov Andriy, Christ-Crain Mirjam, Thomann Robert, Hoess Claus, Henzen Christoph, Zimmerli Werner, Mueller Beat, Schuetz Philipp (2015), Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia, in CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 53(4), 559-566.
[In Process Citation].
Nigro Nicole, Christ-Crain Mirjam, Meier Christian (2014), [In Process Citation]., in Therapeutische Umschau. Revue thérapeutique, 71(4), 229-37.
A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis.
Fenske Wiebke Kristin, Christ-Crain Mirjam, Hörning Anna, Simet Jessica, Szinnai Gabor, Fassnacht Martin, Rutishauser Jonas, Bichet Daniel G, Störk Stefan, Allolio Bruno (2014), A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis., in Journal of the American Society of Nephrology : JASN, 25(10), 2376-83.
Adenovirus-specific IgG maturation as a surrogate marker in acute exacerbations of COPD.
Boeck Lucas, Gencay Mikael, Roth Michael, Hirsch Hans H, Christ-Crain Mirjam, Mueller Beat, Tamm Michael, Stolz Daiana (2014), Adenovirus-specific IgG maturation as a surrogate marker in acute exacerbations of COPD., in Chest, 146(2), 339-47.
Association of adrenal function and disease severity in community-acquired pneumonia.
Mueller Cornelia, Blum Claudine A, Trummler Michael, Stolz Daiana, Bingisser Roland, Mueller Christian, Tamm Michael, Mueller Beat, Schuetz Philipp, Christ-Crain Mirjam (2014), Association of adrenal function and disease severity in community-acquired pneumonia., in PloS one, 9(6), 99518-99518.
BNP but Not s-cTnln is associated with cardioembolic aetiology and predicts short and long term prognosis after cerebrovascular events.
Nigro Nicole, Wildi Karin, Mueller Christian, Schuetz Philipp, Mueller Beat, Fluri Felix, Christ-Crain Mirjam, Katan Mira (2014), BNP but Not s-cTnln is associated with cardioembolic aetiology and predicts short and long term prognosis after cerebrovascular events., in PloS one, 9(7), 102704-102704.
Copeptin Concentrations During Psychological Stress: the PsyCo Study.
Siegenthaler Judith, Walti Carla, Urwyler Sandrine Andrea, Schuetz Philipp, Christ-Crain Mirjam (2014), Copeptin Concentrations During Psychological Stress: the PsyCo Study., in European journal of endocrinology / European Federation of Endocrine Societies, 737-742.
Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study.
De Marchis Gian Marco, Weck Anja, Audebert Heinrich, Benik Steffen, Foerch Christian, Buhl Daniela, Schuetz Philipp, Jung Simon, Seiler Marleen, Morgenthaler Nils G, Mattle Heinrich P, Mueller Beat, Christ-Crain Mirjam, Arnold Marcel, Katan Mira (2014), Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study., in Stroke; a journal of cerebral circulation, 45(10), 2918-23.
Copeptin levels are independent of ingested nutrient type after standardised meal administration - the CoMEAL study.
Walti Carla, Siegenthaler Judith, Christ-Crain Mirjam (2014), Copeptin levels are independent of ingested nutrient type after standardised meal administration - the CoMEAL study., in Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, 19(7), 557-62.
Copeptin levels remain unchanged during the menstrual cycle.
Blum Claudine A, Mirza Uzma, Christ-Crain Mirjam, Mueller Beat, Schindler Christian, Puder Jardena J (2014), Copeptin levels remain unchanged during the menstrual cycle., in PloS one, 9(5), 98240-98240.
Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial.
Blum Claudine A, Nigro Nicole, Winzeler Bettina, Suter-Widmer Isabelle, Schuetz Philipp, Briel Matthias, Bingisser Roland, Zimmerli Werner, Ullmer Elke, Elsaesser Hanno, Tarr Philip, Wirz Sebastian, Thomann Robert, Hofmann Eveline, Rodondi Nicolas, Duplain Hervé, Burki Dieter, Mueller Beat, Christ-Crain Mirjam (2014), Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial., in Trials, 15, 257-257.
Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: results from the randomized ProHOSP trial.
Schuetz Philipp, Kutz Alexander, Grolimund Eva, Haubitz Sebastian, Demann Désirée, Vögeli Alaadin, Hitz Fabienne, Christ-Crain Mirjam, Thomann Robert, Falconnier Claudine, Hoess Claus, Henzen Christoph, Marlowe Robert J, Zimmerli Werner, Mueller Beat, ProHOSP Study Group (2014), Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: results from the randomized ProHOSP trial., in International journal of cardiology, 175(3), 464-72.
Isolated insular strokes and plasma MR-proANP levels are associated with newly diagnosed atrial fibrillation: a pilot study.
Frontzek Karl, Fluri Felix, Siemerkus Jakob, Müller Beat, Gass Achim, Christ-Crain Mirjam, Katan Mira (2014), Isolated insular strokes and plasma MR-proANP levels are associated with newly diagnosed atrial fibrillation: a pilot study., in PloS one, 9(3), 92421-92421.
Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.
Grolimund Eva, Kutz Alexander, Marlowe Robert J, Vögeli Alaadin, Alan Murat, Christ-Crain Mirjam, Thomann Robert, Falconnier Claudine, Hoess Claus, Henzen Christoph, Zimmerli Werner, Mueller Beat, Schuetz Philipp, for the ProHOSP Study Group (2014), Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type., in COPD, 00:1-11.
Pre-analytic factors and initial biomarker levels in community-acquired pneumonia patients
Kutz Alexander, Grolimund Eva, Christ-Crain Mirjam, Thomann Robert, Falconnier Claudine, Hoess Claus, Henzen Christoph, Zimmerli Werner, Mueller Beat, Schuetz Philipp (2014), Pre-analytic factors and initial biomarker levels in community-acquired pneumonia patients, in BMC ANESTHESIOLOGY, 14, 102.
Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia.
Zhydkov Andriy, Christ-Crain Mirjam, Thomann Robert, Hoess Claus, Henzen Christoph, Zimmerli Werner, Mueller Beat, Schuetz Philipp (2014), Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia., in Clinical chemistry and laboratory medicine : CCLM / FESCC, 1-8.

Collaboration

Group / person Country
Types of collaboration
St.Bartholomews Hospital London (Prof. A.B. Grossman) Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Willem Jan Bos, Dr. Boersma, Utrecht and Alkmaar Netherlands (Europe)
- Publication
- Research Infrastructure
Prof. D. Annane, University de Versailles France (Europe)
- Publication
Prof. Umberto Meduri, Dr. Sachin Yende, Pittsburgh United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
BICE (Basel Institute of Clinical Epidemiology), Prof. H.C. Bucher Switzerland (Europe)
- Publication
Medizinische Klinik Aarau Switzerland (Europe)
- Publication
- Research Infrastructure
- Exchange of personnel
Emergency Dept. USB, Prof. R. Bingisser Switzerland (Europe)
- Publication
- Exchange of personnel
Medizinische Kliniken Liestal, Bruderholz, Solothurn, Delémont, Inselspital Bern Switzerland (Europe)
- Publication
- Research Infrastructure
Dept. Innere Medizin, USB (Prof. J. Schifferli und Prof. C.Müller) Switzerland (Europe)
- Publication
- Exchange of personnel

Awards

Title Year
Preis der SGIM (Schweizerische Gesellschaft für Innere Medizin) zuhanden von Claudine Blum für Publikation Lancet 2015 (Adjunct prednisone Treatment for community-acquired pneumonia). 2015

Associated projects

Number Title Start Funding scheme
123346 Corticosteroid treatment for Community-Acquired Pneumonia - A randomized, double-blind study- The STEP trial 01.10.2009 SNSF Professorships
162608 Improving Diagnosis and Treatment of Polyuria Polydipsia syndrome 01.10.2015 Project funding (special)
123346 Corticosteroid treatment for Community-Acquired Pneumonia - A randomized, double-blind study- The STEP trial 01.10.2009 SNSF Professorships
173532 A randomised controlled trial of adjunct corticosteroid therapy in hospitalised children with community acquired pneumonia (CAP): THE KIDS-STEP STUDY 01.06.2017 Investigator Initiated Clinical Trials (IICT)

Abstract

Background: Community-acquired pneumonia (CAP) is associated with significant stress with activation of the hypothalamic-pituitary-adrenal (HPA) axis, morbidity and mortality and is the most common cause of death from infectious diseases in developed countries. Mortality rates for CAP have not changed significantly over several decades although new broad-spectrum antibiotics are available, suggesting that other factors are responsible for poor outcome. An abnormal increase in the inflammatory response is associated with poor outcome, and this occurs despite adequate antibiotic therapy. Thus, adjunctive therapies to antibiotics for the treatment of CAP are required. Corticosteroids have an effective intracellular anti-inflammatory activity which is indispensable for survival after exposure to infections. As early as 1955, favorable effects of corticosteroids were reported in patients with pneumococcal pneumonia. A small-sized multicenter randomized trial showed a significant reduction in hospital mortality in severe CAP with a seven-day continuous infusion of hydrocortisone (240mg/d), although this study was not powered for mortality. Another large, but retrospective single center study evaluated more than 300 patients and demonstrated in multivariate analysis that use of corticosteroids was associated with a lower mortality (7). More recently, two randomized controlled trials involving 200-300 patients showed controversial results. Two systematic reviews concluded that the available evidence suggests that administration of corticosteroids in patients with CAP might be beneficial, however, a large and adequately powered randomized trial is warranted to support this benefit before a recommendation can be made with regard to the use of corticosteroids in the treatment of CAP. Study Objectives: The current large and adequately powered randomized double-blind trial will determine the risks and benefits of adding corticosteroids to the treatment of patients with CAP. We will compare a treatment with 7 days of corticosteroids with placebo in patients with CAP with respect to the primary endpoint of time to clinical stability. We hypothesize that use of corticosteroids will lead to a 25% relative risk reduction for death and clinical instability.Study Design & Setting: This is an investigator-initiated, double-blind randomized multicentre trial. All patients hospitalized with CAP will be included and randomized 1:1 either to corticosteroid or to placebo. Due to power calculations, a sample size of 800 (400 per group) will be needed to achieve a statistical power of 85%. We consider loss to follow up for the primary endpoint of clinical stability in this sample of hospitalized patients as unlikely. We intend to recruit the 800 study participants from December 2009 to June 2014. Centers: University Hospital Basel, cantonal hospitals of Bruderholz, Liestal, Aarau, Solothurn and Delémont, University Hospital Bern (Inselspital Bern). Study participants:Inclusion criteria: Patients 18 years of age or older admitted for hospitalization from the community or a nursing home with CAP. CAP is defined by a new infiltrate on chest radiograph and the presence of one or several of the following acute respiratory signs or symptoms, cough, sputum production, dyspnea, core body temperature >38.0° C, auscultatory findings of abnormal breath sounds and rales and leukocyte count >10 or <4 x 109 cells L-1. Exclusion criteria: Patients permanently unable to give written informed consent, e.g. with severe dementia, other permanent cognitive impairment or legal guardian; Patients with active intravenous drug use; severe immunosuppression; patients with cystic fibrosis as well as patients with active tuberculosis; patients with acute burn injury; patients with acute gastrointestinal bleeding within 3 months of the current hospitalization; patients with a condition requiring more than 0.5mg/kg/d prednisone equivalent; pregnancy or breast feeding; patients with known adrenal insufficiency. Intervention: All patients with community-acquired pneumonia willing to participate in the study are randomized to either corticosteroid treatment or placebo treatment for 7 days. Clinical stability is monitored 12 hourly and blood sampling is performed at days 3, 5 and 7. At day 30 and 180 all patients have a telephone follow-up interview. Study endpoints: Primary Endpoint: The primary endpoint is time to clinical stability. Time to clinical stability is defined as follows: time (days) until stable vital signs (16) for > 24h: Temperature < 37.8°C, heart rate/minute <100, spontaneous respiratory rate < 24 per minute, systolic blood pressure > 90mmHg mental status back to level before CAP, adequate oxygenation on room air of oxygen therapy (PaO2>60mmHg or pulse oxymetry > 90%). Blinded study personnel will check for clinical stability every 12 hours. Secondary Endpoints:- a) Mortality - b) Need for ICU stay - c) Side effects of corticosteroid treatment (i.e. rate of hyperglycemia, hypertension, nosocomial infections, recurrence, weight gain)- d) Value of adrenal function testing (ACTH test) and of prognostic hormonal biomarkers (e.g. total and free cortisol levels, copeptin, dehydroepiandrosterone (DHEA) as well as the ratio of cortisol to DHEA (4)) to identify those patients who benefit from corticosteroid treatment.- e) Effect of corticosteroid treatment on laboratory markers of infection, i.e. procalcitonin, C-reactive protein, interleukin and cytokine levels and on candidate genetic variants potentially associated with response. Working hypotheses for primary and secondary endpoints: 1.Use of corticosteroids will lead to a 25% relative risk reduction for death and clinical instability.2.Mortality rate will tend to decrease in the corticosteroid group as compared to placebo treatment.3.Need for ICU stay will tend to decrease in the corticosteroid group as compared to placebo treatment.4.Patients in the steroid group will have a higher rate of steroid induced hyperglycemia (as defined as fasting glucose level > 7mmol/L or postprandial glucose level > 11.1 mmol/L). Myopathy (as surrogate parameters urea and creatinine will be measured in plasma) and nosocomial infections will be similar in both groups.5.Adrenal function testing (i.e. 1ug ACTH test) will not be able to identifying those patients who benefit from corticosteroid treatment. Prognostic hormonal markers and the ratio of cortisol to DHEA will have a better accuracy to identify patients profiting from corticosteroid treatment. 6.Corticosteroid treatment will lead to a more rapid normalization of laboratory surrogates of infection, i.e. procalcitonin, C-reactive protein, interleukin levels and TNF-alpha.Significance:Data about corticosteroid use in patients with CAP are controversial and derive from small data sets. This large multicenter double-blind trial will give conclusive answers about risks and benefits of corticosteroid treatment in CAP.
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