Hydrocortisone for Prevention of Septic Shock (HYPRESS)

This study is currently recruiting participants.

Verified November 2012 by Charite University, Berlin, Germany

Sponsor:

Collaborators:

German Federal Ministry of Education and Research

German Competence Network Sepsis

Coordination Center for Clinical Studies Leipzig (KKSL)

Information provided by (Responsible Party):

Didier Keh, Charite University, Berlin, Germany

ClinicalTrials.gov Identifier:

NCT00670254

First received: April 29, 2008

Last updated: November 13, 2012

Last verified: November 2012

History of Changes

Purpose

Severe sepsis is a disease with a high mortality. Development of shock is a most serious complication and increases the risk of death considerably. Application of low dose hydrocortisone is currently recommended only in patients after severe septic shock has been established. Hydrocortisone therapy has a hemodynamic stabilizing effect and may reverse shock, however, the preventive application has not been investigated in a larger study. The study investigates whether low dose hydrocortisone prevents the development of shock in patients with severe sepsis. It is postulated that shock prevention may also affect morbidity and mortality.

Condition	Intervention	Phase
Severe Sepsis	Drug: Placebo Drug: Hydrocortisone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Placebo-controlled, Randomised, Double-blind Study to Investigate the Efficacy and Safety of Low Dose Hydrocortisone to Prevent the Development of Septic Shock in Patients With Severe Sepsis

Resource links provided by NLM:

MedlinePlus related topics: Sepsis Shock

Drug Information available for: Hydrocortisone acetate Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Hydrocortisone butyrate Hydrocortisone valerate Hydrocortisone probutate

U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Septic shock [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mortality [ Time Frame: 28, 90, and 180 days; ICU and hospital ] [ Designated as safety issue: No ]
Length of stay [ Time Frame: ICU and hospital (3-6 months) ] [ Designated as safety issue: No ]
Time to death [ Time Frame: 28, 90, and 180 days ] [ Designated as safety issue: No ]
Time to septic shock [ Time Frame: 14 days ] [ Designated as safety issue: No ]
Mechanical ventilation [ Time Frame: until ICU discharge ] [ Designated as safety issue: No ]
Renal replacement therapy [ Time Frame: until ICU discharge ] [ Designated as safety issue: No ]
Organ dysfunction (SOFA score) [ Time Frame: until ICU discharge but day 14 at maximum ] [ Designated as safety issue: No ]
Frequency of weaning failure [ Time Frame: until ICU discharge ] [ Designated as safety issue: Yes ]
Frequency and severity of muscle weakness [ Time Frame: until ICU discharge ] [ Designated as safety issue: Yes ]
Frequency of gastrointestinal bleeding [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Frequency of secondary infections [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Delir [ Time Frame: ICU discharge ] [ Designated as safety issue: Yes ]
Hypernatremia [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
Hyperglycemia [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
Other adverse events [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Posttraumatic stress disorder / health-related quality of life [ Time Frame: Hosptal discharge and 180 days after hospital discharge ] [ Designated as safety issue: No ]
Immune response to hydrocortisone [ Time Frame: 6 days ] [ Designated as safety issue: No ]
Adrenal function [ Time Frame: baseline ] [ Designated as safety issue: No ]

Estimated Enrollment:	380
Study Start Date:	January 2009
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Hydrocortisone	Drug: Hydrocortisone 50 mg loading dose, continuous infusion of 200 mg/d for 5 d, 100 mg/d for 2d, 50 mg/d for 2 d, and 25 mg/d for 2 d.
Placebo Comparator: Placebo	Drug: Placebo Application is identical to experimental arm

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Severe sepsis according to ACCP/CCM criteria
Onset of severe sepsis < 48 hours
Informed consent
Effective contraception in fertile women

Exclusion Criteria:

Septic shock
Known hypersensitivity to hydrocortisone and additives
Glucocorticoid history which warrants continuation of glucocorticoid administration
Other indication for systemic glucocorticoid therapy
DNR-order
Moribund patient
Pregnancy
Breast feeding women
Age < 18 years
Other interventional study
Relationship to investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670254

Contacts

Contact: Didier Keh, MD	++49 30 450 651048	didier.keh@charite.de
Contact: Frank M Brunkhorst, MD	+49 3641 9323383	frank.brunkhorst@med.uni-jena.de

Locations

Germany
Universitaetsklinikum Aachen, Operative Intensivmedizin Erwachsene	Recruiting
Aachen, Germany, 52074
Contact: Gernot Marx, MD +49 241 8080444 gmarx@ukaachen.de
Zentralklinik Bad Berka GmbH, Zentrum für Anaesthesie, Intensivtherapie und Notfallmedizin	Recruiting
Bad Berka, Germany, 99437
Contact: Lars Hüter, MD +49 36458 51001 lars.hueter@zentralklinik.de
HELIOS Klinikum Bad Saarow; Zentrum für Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie	Recruiting
Bad Saarow, Germany, 15526
Contact: Stefan P Wirtz, MD +49 33631 73181 stefan.wirtz@helios-kliniken.de
Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Med. Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin	Recruiting
Berlin, Germany, 13353
Contact: Sibylle Rademacher, MD +49 30 450 665516 sibylle.rademacher@charite.de
Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Campus Mitte, Med. Klinik mit Schwerpunkt Infektiologie und Pneumologie	Terminated
Berlin, Germany, 13353
Vivantes Klinikum Hellersdorf, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie	Terminated
Berlin, Germany, 12621
St. Joseph Krankenhaus, Institut fue Anaesthesie, Schwerpunkt operative Intensivmedizin und SchmerztherapieAnaesthesie, operative Intensiv- und Notfallmedizin	Recruiting
Berlin, Germany, 12101
Contact: Martin Schmutzler, MD +49 30 78822384 dr.schmutzler@t-online.de
Vivantes Klinikum-Neukoelln, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie	Recruiting
Berlin, Germany, 12351
Contact: Herwig Gerlach, MD +49 30 130142011 herwig.gerlach@vivantes.de
Vivantes Klinikum Neukoelln,Klinik fuer Innere Medizin, Kardiologie und konservative Intensivmedizin	Terminated
Berlin, Germany, 12351
Vivantes Humboldt-Klinikum, Klinik für Innere Medizin - Kardiologie und konservative Intensivmedizin	Recruiting
Berlin, Germany, 13509
Contact: Josefa Lehmke, MD +49 30 130121011 josefa.lehmke@vivantes.de
Vivantes Humboldt Klinikum, Klink fuer Anaesthesie, opertaive Intensivmedizin und Schmerztherapie	Withdrawn
Berlin, Germany, 13509
Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Mitte Klinik für Anaesthesiologie und operative Intensivmedizin	Recruiting
Berlin, Germany, 13353
Contact: Didier Keh, MD +49 30 450 651048 didier.keh@charite.de
Vivantes Auguste-Viktoria-Klinikum, Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie	Terminated
Berlin, Germany, 12157
Helios Klinikum Berlin Buch, Klinik für Intensivmedizin	Recruiting
Berlin, Germany, 13125
Contact: Kerstin Resener, MD +49 30 940113105 kerstin.resener@helios-kliniken.de
Rheinische Friedrich-Wilhelms-Universitaet, Klinik für Anaesthesiologie und Operative Intensivmedizin	Terminated
Bonn, Germany, 53105
Krankenhaus Dresden-Friedrichstadt, Klinik für Anaesthesiologie und Intensivmedizin	Recruiting
Dresden, Germany, 01067
Contact: Andreas Nowak, MD +49 351 4801170 nowak-an@khdf.de
Universitaetsklinik Carl Gustav Carus Dresden	Recruiting
Dresden, Germany, 01307
Contact: Maximilian Ragaller, MD +49 351 4582785 maximillian.ragaller@uniklinikum-dresden.de
Helios Klinikum Erfurt, Klinik fuer Anaesthesie, Intensivmedizin und Schmerztherapie	Recruiting
Erfurt, Germany, 99089
Contact: Andreas Meier-Hellmann, MD +49 361 7816076 andreas.meier-hellmann@helios-kliniken.de
Universitaetsklinikum Freiburg, Anaesthesiologische Universitaetsklinik - Abteilung Anaesthesiologie und Intensivtherapie	Terminated
Freiburg, Germany, 79106
Ernst Moritz Arndt Universitaet Greifswald, Klinik und Poliklinik für Anaesthesiologie und Intensivmedizin	Recruiting
Greifswald, Germany, 17475
Contact: Matthias Gruendling, MD +49 383 4865810 gruendli@uni-greifswald.de
Medizinische Fakultaet der Martin-Luther-Universitaet Halle-Wittenberg - Universitaetsklinikum Halle (Saale)	Recruiting
Halle (Saale), Germany, 06097
Contact: Michael Bucher, MD +49 345 5572322 michael.bucher@uk-halle.de
Krankenhaus Martha-Maria Halle-Doelau GmbH	Recruiting
Halle (Saale), Germany, 06120
Contact: Harald Fritz, MD +49 345 5591255 harald.fritz@martha-maria.de
Universitaetsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin	Recruiting
Hamburg, Germany, 20246
Contact: Axel Nierhaus, MD +49 40 428037010 nierhaus@uke.de
Universitaetsklinikum Heidelberg, Innere Medizin IV: Gastroenterologie, Infektionskrankheiten, Vergiftungen	Withdrawn
Heidelberg, Germany, 69120
Klinikum Heidenheim, Klinik für Anaesthesiologie und operative Intensivmedizin	Recruiting
Heidenheim, Germany, 89522
Contact: Alexander Brinkmann, MD +49 7321 332212 alexander.brinkmann@kliniken-heidenheim.de
Klinik Henningsdorf der Oberhavel-Kliniken GmbH, Abteilung für Anaesthesie und Intensivmedizin	Terminated
Henningsdorf, Germany, 16716
Klinikum Hildesheim GmbH, Klinik fuer Kardiologie, Angiologie, Intensivmedizin	Withdrawn
Hildesheim, Germany, 31134
Universitätsklinikum des Saarlandes	Withdrawn
Homburg/Saar, Germany, 66421
Friedrich Schiller Universität, Klinik für Anaesthesiologie und Intensivmedizin	Recruiting
Jena, Germany, 07747
Contact: Konrad Reinhart, MD +49 341 9323102 konrad.reinhart@med.uni-jena.de
Universitaetsklinikum Schleswig Holstein Campus Kiel, Klinik für Anaesthesiologie und Operative Intensivmedizin	Recruiting
Kiel, Germany, 24105
Contact: Norbert Weiler, MD +49 431 5972991 norbert.weiler@uksh.de
Klinikum der Universitaet zu Koeln, Medizinische Klinik I: Innere Medizin	Withdrawn
Koeln, Germany, 50294
Kliniken der Stadt Koeln - Krankenhaus Merheim, Klinik für Anaesthesiologie und operative Intensivmedizin	Recruiting
Koeln, Germany, 51058
Contact: Frank Wappler, MD +49 221 89073863 wapplerf@kliniken-koeln.de
St. Elisabeth-Krankenhaus Köln-Hohenlind, Klinik für Anaesthesiologie und operative Intensivmedizin	Recruiting
Koeln, Germany, 50935
Contact: Fritz Fiedler, MD +49 221 46771701 fritz.fiedler@hohenlind.de
Universitaetsklinikum Leipzig AöR, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie	Recruiting
Leipzig, Germany, 04103
Contact: Sven Bercker, MD +49 341 9717704 sven.bercker@uniklinik-leipzig.de
Universitaetsklinikum Mannheim, I. Medizinische Klinik: Kardiologie, Angiologie, Pneumologie	Withdrawn
Mannheim, Germany, 68167
Universitaetsklinikum Mannheim, Klinik für Anaesthesiologie und operative Intensivmedizin	Withdrawn
Mannheim, Germany, 68167
Universitaetsklinikum Giessen und Marburg GmbH, Standort Marburg, Klinik für Innere Medizin, Schwerpunkt Pneumologie	Withdrawn
Marburg, Germany, 35043
Klinikum Nuernberg-Nord, Klinik für Anaesthesiologie und operative Intensivmedizin	Withdrawn
Nuernberg, Germany, 90419
Klinikum Oldenburg GmbH, Klinik fuer Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie	Recruiting
Oldenburg, Germany, 26133
Contact: Andreas Weyland, MD +49 441 4032571 weyland.andreas@klinikum-oldenburg.de
Klinikum Ernst von Bergmann GmbH, Klinik für Anaesthesie und Intensivtherapie	Withdrawn
Potsdam, Germany, 14467
Rostock Universitaetsklinikum, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie	Withdrawn
Rostock, Germany, 18057
Universitaetsklinikum Ulm, Klinik für Anaesthesiologie	Withdrawn
Ulm, Germany, 89075

Sponsors and Collaborators

Charite University, Berlin, Germany

German Federal Ministry of Education and Research

German Competence Network Sepsis

Coordination Center for Clinical Studies Leipzig (KKSL)

Investigators

Principal Investigator:	Konrad Reinhart, MD	University Hospital Jena; Dept. of Anesthesiology an Intensive Care Medicine
Study Chair:	Didier Keh, MD	Charité Universitaetsmedizin Berlin, Dept. of Anesthsiology and Intensive Care Medicine
Study Director:	Frank M Brunkhorst, MD	University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine
Study Director:	Markus Loeffler, MD	University Leipzig, Coordination Center of Clinical Studies (KKSL)

More Information

Additional Information:

Competence Network Sepsis (SepNet) This link exits the ClinicalTrials.gov site

Publications:

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan;36(1):296-327. Erratum in: Crit Care Med. 2008 Apr;36(4):1394-6.

Reinhart K, Brunkhorst F, Bone H, Gerlach H, Gründling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Quintel M, Ragaller M, Rossaint R, Stüber F, Weiler N, Welte T, Werdan K; Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI); Deutschen Sepsis-Gesellschaft e.V. (DSG). [Diagnosis and therapy of sepsis. Guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine] Internist (Berl). 2006 Apr;47(4):356, 358-60, 362-8, passim. Review. German.

Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, Gruendling M, Huhle G, Jaschinski U, John S, Mayer K, Oppert M, Olthoff D, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Bogatsch H, Hartog C, Loeffler M, Reinhart K. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med. 2007 Apr;33(4):606-18. Epub 2007 Feb 24.

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008 Jan 10;358(2):111-24.

Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev. 2004;(1):CD002243. Review.

Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Volk HD, Doecke WD, Falke KJ, Gerlach H. Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med. 2003 Feb 15;167(4):512-20. Epub 2002 Nov 8.

[No authors listed] American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74. Review.

Responsible Party:	Didier Keh, MD, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00670254 History of Changes
Other Study ID Numbers:	HYPRESS, BMBF grant: 01KG0701, EudraCT-No: 2007-004401-10
Study First Received:	April 29, 2008
Last Updated:	November 13, 2012
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

Sepsis
Septic
Shock
Glucocorticoids
Hydrocortisone

Additional relevant MeSH terms:

Sepsis
Toxemia
Shock
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Cortisol succinate

Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on May 23, 2013

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