Hydrocortisone for Prevention of Septic Shock

NCT ID: NCT00670254

Last Updated: 2013-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

380 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2013-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Severe Sepsis

Keywords

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Sepsis Septic Shock Glucocorticoids Hydrocortisone

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Hydrocortisone

Group Type EXPERIMENTAL

Hydrocortisone

Intervention Type 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.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Application is identical to experimental arm

Interventions

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Placebo

Application is identical to experimental arm

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

SepNet - Critical Care Trials Group

OTHER

Sponsor Role collaborator

Coordination Centre for Clinical Trials Leipzig

UNKNOWN

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role lead

Responsible Party

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Didier Keh

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Konrad Reinhart, MD

Role: PRINCIPAL_INVESTIGATOR

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

Didier Keh, MD

Role: STUDY_CHAIR

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

Frank M Brunkhorst, MD

Role: STUDY_DIRECTOR

University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine

Markus Loeffler, MD

Role: STUDY_DIRECTOR

University Leipzig, Coordination Center of Clinical Studies (KKSL)

Locations

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Universitaetsklinikum Aachen, Operative Intensivmedizin Erwachsene

Aachen, , Germany

Site Status

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

Bad Berka, , Germany

Site Status

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

Bad Saarow, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

Helios Klinikum Berlin Buch, Klinik für Intensivmedizin

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Berlin, , Germany

Site Status

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

Bonn, , Germany

Site Status

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

Cologne, , Germany

Site Status

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

Cologne, , Germany

Site Status

Krankenhaus Dresden-Friedrichstadt, Klinik für Anaesthesiologie und Intensivmedizin

Dresden, , Germany

Site Status

Universitaetsklinik Carl Gustav Carus Dresden

Dresden, , Germany

Site Status

Helios Klinikum Erfurt, Klinik fuer Anaesthesie, Intensivmedizin und Schmerztherapie

Erfurt, , Germany

Site Status

Universitaetsklinikum Freiburg, Anaesthesiologische Universitaetsklinik - Abteilung Anaesthesiologie und Intensivtherapie

Freiburg im Breisgau, , Germany

Site Status

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

Greifswald, , Germany

Site Status

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

Halle, , Germany

Site Status

Krankenhaus Martha-Maria Halle-Doelau GmbH

Halle, , Germany

Site Status

Universitaetsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin

Hamburg, , Germany

Site Status

Klinikum Heidenheim, Klinik für Anaesthesiologie und operative Intensivmedizin

Heidenheim, , Germany

Site Status

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

Henningsdorf, , Germany

Site Status

Friedrich Schiller Universität, Klinik für Anaesthesiologie und Intensivmedizin

Jena, , Germany

Site Status

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

Kiel, , Germany

Site Status

Universitaetsklinikum Leipzig AöR, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie

Leipzig, , Germany

Site Status

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

Oldenburg, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 18158437 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16532281 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17323051 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18184957 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14973984 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12426230 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1597042 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36345013 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27695824 (View on PubMed)

Related Links

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Other Identifiers

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01KG0701

Identifier Type: OTHER

Identifier Source: secondary_id

2007-004401-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HYPRESS

Identifier Type: -

Identifier Source: org_study_id