Hydrocortisone for Prevention of Septic Shock

Severe Sepsis Clinical Trial

— HYPRESS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00670254
• Other study ID #: HYPRESS
• Secondary ID: 01KG07012007-004
• Status: Completed
• Phase: Phase 3
• First received: April 29, 2008
• Last updated: September 26, 2013
• Start date: January 2009
• Est. completion date: August 2013

Study information

• Verified date: September 2013
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Sepsis
• Severe Sepsis

Intervention

Drug:
• Placebo
Application is identical to experimental arm
• 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.

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Aachen, Operative Intensivmedizin Erwachsene	Aachen
Germany	Zentralklinik Bad Berka GmbH, Zentrum für Anaesthesie, Intensivtherapie und Notfallmedizin	Bad Berka
Germany	HELIOS Klinikum Bad Saarow; Zentrum für Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie	Bad Saarow
Germany	Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Campus Mitte, Med. Klinik mit Schwerpunkt Infektiologie und Pneumologie	Berlin
Germany	Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Mitte Klinik für Anaesthesiologie und operative Intensivmedizin	Berlin
Germany	Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Med. Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin	Berlin
Germany	Helios Klinikum Berlin Buch, Klinik für Intensivmedizin	Berlin
Germany	St. Joseph Krankenhaus, Institut fue Anaesthesie, Schwerpunkt operative Intensivmedizin und SchmerztherapieAnaesthesie, operative Intensiv- und Notfallmedizin	Berlin
Germany	Vivantes Auguste-Viktoria-Klinikum, Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie	Berlin
Germany	Vivantes Humboldt-Klinikum, Klinik für Innere Medizin - Kardiologie und konservative Intensivmedizin	Berlin
Germany	Vivantes Klinikum Hellersdorf, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie	Berlin
Germany	Vivantes Klinikum Neukoelln,Klinik fuer Innere Medizin, Kardiologie und konservative Intensivmedizin	Berlin
Germany	Vivantes Klinikum-Neukoelln, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie	Berlin
Germany	Rheinische Friedrich-Wilhelms-Universitaet, Klinik für Anaesthesiologie und Operative Intensivmedizin	Bonn
Germany	Krankenhaus Dresden-Friedrichstadt, Klinik für Anaesthesiologie und Intensivmedizin	Dresden
Germany	Universitaetsklinik Carl Gustav Carus Dresden	Dresden
Germany	Helios Klinikum Erfurt, Klinik fuer Anaesthesie, Intensivmedizin und Schmerztherapie	Erfurt
Germany	Universitaetsklinikum Freiburg, Anaesthesiologische Universitaetsklinik - Abteilung Anaesthesiologie und Intensivtherapie	Freiburg
Germany	Ernst Moritz Arndt Universitaet Greifswald, Klinik und Poliklinik für Anaesthesiologie und Intensivmedizin	Greifswald
Germany	Krankenhaus Martha-Maria Halle-Doelau GmbH	Halle (Saale)
Germany	Medizinische Fakultaet der Martin-Luther-Universitaet Halle-Wittenberg - Universitaetsklinikum Halle (Saale)	Halle (Saale)
Germany	Universitaetsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin	Hamburg
Germany	Klinikum Heidenheim, Klinik für Anaesthesiologie und operative Intensivmedizin	Heidenheim
Germany	Klinik Henningsdorf der Oberhavel-Kliniken GmbH, Abteilung für Anaesthesie und Intensivmedizin	Henningsdorf
Germany	Friedrich Schiller Universität, Klinik für Anaesthesiologie und Intensivmedizin	Jena
Germany	Universitaetsklinikum Schleswig Holstein Campus Kiel, Klinik für Anaesthesiologie und Operative Intensivmedizin	Kiel
Germany	Kliniken der Stadt Koeln - Krankenhaus Merheim, Klinik für Anaesthesiologie und operative Intensivmedizin	Koeln
Germany	St. Elisabeth-Krankenhaus Köln-Hohenlind, Klinik für Anaesthesiologie und operative Intensivmedizin	Koeln
Germany	Universitaetsklinikum Leipzig AöR, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie	Leipzig
Germany	Klinikum Oldenburg GmbH, Klinik fuer Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie	Oldenburg

Sponsors (4)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Coordination Centre for Clinical Trials Leipzig, German Competence Network Sepsis, German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

References & Publications (7)

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. — View Citation

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. Update in: Cochrane Database Syst Rev. 2015;12:CD002243. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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

External Links

•   Competence Network Sepsis (SepNet)