Hydrocortisone for Prevention of Septic Shock

NCT00670254 | Completed Phase 3 DMC

• 3 other identifiers: HYPRESS01KG07012007-004401-10
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 30

Brief 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.

Conditions

Severe Sepsis

Keywords

Sepsis; Septic; Shock; Glucocorticoids; Hydrocortisone

Outcome Measures

Primary Outcomes (1)

• Septic shock

  14 days

Secondary Outcomes (18)

• Mortality

  28, 90, and 180 days; ICU and hospital

• Length of stay

  ICU and hospital (3-6 months)

• Time to death

  28, 90, and 180 days

• Time to septic shock

  14 days

• Mechanical ventilation

  until ICU discharge

Study Arms (2)

Hydrocortisone

EXPERIMENTAL

Drug: Hydrocortisone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

Application is identical to experimental arm

Placebo

Hydrocortisone DRUG

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.

Hydrocortisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• German Federal Ministry of Education and Research: collaborator
• SepNet - Critical Care Trials Group: collaborator
• Coordination Centre for Clinical Trials Leipzig: collaborator

Study Sites (30)

Universitaetsklinikum Aachen, Operative Intensivmedizin Erwachsene

Aachen, 52074, Germany

Location

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

Bad Berka, 99437, Germany

Location

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

Bad Saarow, 15526, Germany

Location

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

Berlin, 12101, Germany

Location

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

Berlin, 12157, Germany

Location

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

Berlin, 12351, Germany

Location

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

Berlin, 12351, Germany

Location

Vivantes Klinikum Hellersdorf, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie

Berlin, 12621, Germany

Location

Helios Klinikum Berlin Buch, Klinik für Intensivmedizin

Berlin, 13125, Germany

Location

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

Berlin, 13353, Germany

Location

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

Berlin, 13353, Germany

Location

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

Berlin, 13353, Germany

Location

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

Berlin, 13509, Germany

Location

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

Bonn, 53105, Germany

Location

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

Cologne, 50935, Germany

Location

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

Cologne, 51058, Germany

Location

Krankenhaus Dresden-Friedrichstadt, Klinik für Anaesthesiologie und Intensivmedizin

Dresden, 01067, Germany

Location

Universitaetsklinik Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Helios Klinikum Erfurt, Klinik fuer Anaesthesie, Intensivmedizin und Schmerztherapie

Erfurt, 99089, Germany

Location

Universitaetsklinikum Freiburg, Anaesthesiologische Universitaetsklinik - Abteilung Anaesthesiologie und Intensivtherapie

Freiburg im Breisgau, 79106, Germany

Location

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

Greifswald, 17475, Germany

Location

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

Halle, 06097, Germany

Location

Krankenhaus Martha-Maria Halle-Doelau GmbH

Halle, 06120, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin

Hamburg, 20246, Germany

Location

Klinikum Heidenheim, Klinik für Anaesthesiologie und operative Intensivmedizin

Heidenheim, 89522, Germany

Location

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

Henningsdorf, 16716, Germany

Location

Friedrich Schiller Universität, Klinik für Anaesthesiologie und Intensivmedizin

Jena, 07747, Germany

Location

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

Kiel, 24105, Germany

Location

Universitaetsklinikum Leipzig AöR, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie

Leipzig, 04103, Germany

Location

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

Oldenburg, 26133, Germany

Location

Related Publications (9)

• 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. doi: 10.1097/01.CCM.0000298158.12101.41.

  PMID: 18158437 BACKGROUND

• Reinhart K, Brunkhorst F, Bone H, Gerlach H, Grundling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Werdan K; Deutschen Interdisziplinaren Vereinigung fur 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. doi: 10.1007/s00108-006-1595-x. German.

  PMID: 16532281 BACKGROUND

• 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. doi: 10.1007/s00134-006-0517-7. Epub 2007 Feb 24.

  PMID: 17323051 BACKGROUND

• 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.

  PMID: 18184957 BACKGROUND

• 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. doi: 10.1002/14651858.CD002243.pub2.

  PMID: 14973984 BACKGROUND

• 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. doi: 10.1164/rccm.200205-446OC. Epub 2002 Nov 8.

  PMID: 12426230 BACKGROUND

• 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.

  PMID: 1597042 BACKGROUND

• Briegel J, Mohnle P, Keh D, Lindner JM, Vetter AC, Bogatsch H, Lange D, Frank S, Hinske LC, Annane D, Vogeser M; SepNet Critical Care Trials Group. Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study. Crit Care. 2022 Nov 7;26(1):343. doi: 10.1186/s13054-022-04224-5.

  PMID: 36345013 DERIVED

• Keh D, Trips E, Marx G, Wirtz SP, Abduljawwad E, Bercker S, Bogatsch H, Briegel J, Engel C, Gerlach H, Goldmann A, Kuhn SO, Huter L, Meier-Hellmann A, Nierhaus A, Kluge S, Lehmke J, Loeffler M, Oppert M, Resener K, Schadler D, Schuerholz T, Simon P, Weiler N, Weyland A, Reinhart K, Brunkhorst FM; SepNet-Critical Care Trials Group. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA. 2016 Nov 1;316(17):1775-1785. doi: 10.1001/jama.2016.14799.

  PMID: 27695824 DERIVED

Related Links

• Competence Network Sepsis (SepNet)

MeSH Terms

Conditions

Sepsis; Shock

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Konrad Reinhart, MD

  University Hospital Jena; Dept. of Anesthesiology an Intensive Care Medicine

  PRINCIPAL INVESTIGATOR

• Didier Keh, MD

  Charité Universitaetsmedizin Berlin, Dept. of Anesthsiology and Intensive Care Medicine

  STUDY CHAIR

• 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)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 1, 2008
• Study Start: January 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 27, 2013

Record last verified: 2013-09

Locations

DE (30)