Hydrocortisone for Prevention of Septic Shock

Condition(s) targeted: Severe Sepsis

Intervention: Placebo (Drug); Hydrocortisone (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Charite University, Berlin, Germany

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

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Septic shock

Secondary outcome:

Mortality

Length of stay

Time to death

Time to septic shock

Mechanical ventilation

Renal replacement therapy

Organ dysfunction (SOFA score)

Frequency of weaning failure

Frequency and severity of muscle weakness

Frequency of gastrointestinal bleeding

Frequency of secondary infections

Delir

Hypernatremia

Hyperglycemia

Other adverse events

Posttraumatic stress disorder / health-related quality of life

Immune response to hydrocortisone

Adrenal function

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Universitaetsklinikum Aachen, Operative Intensivmedizin Erwachsene, Aachen 52074, Germany

Zentralklinik Bad Berka GmbH, Zentrum für Anaesthesie, Intensivtherapie und Notfallmedizin, Bad Berka 99437, Germany

HELIOS Klinikum Bad Saarow; Zentrum für Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Bad Saarow 15526, Germany

Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Campus Mitte, Med. Klinik mit Schwerpunkt Infektiologie und Pneumologie, Berlin 13353, Germany

Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Mitte Klinik für Anaesthesiologie und operative Intensivmedizin, Berlin 13353, Germany

Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Med. Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin, Berlin 13353, Germany

Helios Klinikum Berlin Buch, Klinik für Intensivmedizin, Berlin 13125, Germany

St. Joseph Krankenhaus, Institut fue Anaesthesie, Schwerpunkt operative Intensivmedizin und SchmerztherapieAnaesthesie, operative Intensiv- und Notfallmedizin, Berlin 12101, Germany

Vivantes Auguste-Viktoria-Klinikum, Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie, Berlin 12157, Germany

Vivantes Humboldt-Klinikum, Klinik für Innere Medizin - Kardiologie und konservative Intensivmedizin, Berlin 13509, Germany

Vivantes Klinikum Hellersdorf, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie, Berlin 12621, Germany

Vivantes Klinikum Neukoelln,Klinik fuer Innere Medizin, Kardiologie und konservative Intensivmedizin, Berlin 12351, Germany

Vivantes Klinikum-Neukoelln, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie, Berlin 12351, Germany

Rheinische Friedrich-Wilhelms-Universitaet, Klinik für Anaesthesiologie und Operative Intensivmedizin, Bonn 53105, Germany

Krankenhaus Dresden-Friedrichstadt, Klinik für Anaesthesiologie und Intensivmedizin, Dresden 01067, Germany

Universitaetsklinik Carl Gustav Carus Dresden, Dresden 01307, Germany

Helios Klinikum Erfurt, Klinik fuer Anaesthesie, Intensivmedizin und Schmerztherapie, Erfurt 99089, Germany

Universitaetsklinikum Freiburg, Anaesthesiologische Universitaetsklinik - Abteilung Anaesthesiologie und Intensivtherapie, Freiburg 79106, Germany

Ernst Moritz Arndt Universitaet Greifswald, Klinik und Poliklinik für Anaesthesiologie und Intensivmedizin, Greifswald 17475, Germany

Krankenhaus Martha-Maria Halle-Doelau GmbH, Halle (Saale) 06120, Germany

Medizinische Fakultaet der Martin-Luther-Universitaet Halle-Wittenberg - Universitaetsklinikum Halle (Saale), Halle (Saale) 06097, Germany

Universitaetsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin, Hamburg 20246, Germany

Klinikum Heidenheim, Klinik für Anaesthesiologie und operative Intensivmedizin, Heidenheim 89522, Germany

Klinik Henningsdorf der Oberhavel-Kliniken GmbH, Abteilung für Anaesthesie und Intensivmedizin, Henningsdorf 16716, Germany

Friedrich Schiller Universität, Klinik für Anaesthesiologie und Intensivmedizin, Jena 07747, Germany

Universitaetsklinikum Schleswig Holstein Campus Kiel, Klinik für Anaesthesiologie und Operative Intensivmedizin, Kiel 24105, Germany

Kliniken der Stadt Koeln - Krankenhaus Merheim, Klinik für Anaesthesiologie und operative Intensivmedizin, Koeln 51058, Germany

St. Elisabeth-Krankenhaus Köln-Hohenlind, Klinik für Anaesthesiologie und operative Intensivmedizin, Koeln 50935, Germany

Universitaetsklinikum Leipzig AöR, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie, Leipzig 04103, Germany

Klinikum Oldenburg GmbH, Klinik fuer Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Oldenburg 26133, Germany

Competence Network Sepsis (SepNet)

Related 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. doi: 10.1056/NEJMoa071366.

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.

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.

Starting date: January 2009
Last updated: September 26, 2013