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Hydrocortisone for Prevention of Septic Shock (HYPRESS)

Primary Purpose

Severe Sepsis

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Placebo
Hydrocortisone
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Sepsis focused on measuring Sepsis, Septic, Shock, Glucocorticoids, Hydrocortisone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Hydrocortisone

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Septic shock

Secondary Outcome Measures

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

Full Information

First Posted
April 29, 2008
Last Updated
September 26, 2013
Sponsor
Charite University, Berlin, Germany
Collaborators
German Federal Ministry of Education and Research, SepNet - Critical Care Trials Group, Coordination Centre for Clinical Trials Leipzig
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1. Study Identification

Unique Protocol Identification Number
NCT00670254
Brief Title
Hydrocortisone for Prevention of Septic Shock
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
German Federal Ministry of Education and Research, SepNet - Critical Care Trials Group, Coordination Centre for Clinical Trials Leipzig

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis
Keywords
Sepsis, Septic, Shock, Glucocorticoids, Hydrocortisone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
380 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydrocortisone
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Application is identical to experimental arm
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Septic shock
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Mortality
Time Frame
28, 90, and 180 days; ICU and hospital
Title
Length of stay
Time Frame
ICU and hospital (3-6 months)
Title
Time to death
Time Frame
28, 90, and 180 days
Title
Time to septic shock
Time Frame
14 days
Title
Mechanical ventilation
Time Frame
until ICU discharge
Title
Renal replacement therapy
Time Frame
until ICU discharge
Title
Organ dysfunction (SOFA score)
Time Frame
until ICU discharge but day 14 at maximum
Title
Frequency of weaning failure
Time Frame
until ICU discharge
Title
Frequency and severity of muscle weakness
Time Frame
until ICU discharge
Title
Frequency of gastrointestinal bleeding
Time Frame
28 days
Title
Frequency of secondary infections
Time Frame
28 days
Title
Delir
Time Frame
ICU discharge
Title
Hypernatremia
Time Frame
14 days
Title
Hyperglycemia
Time Frame
14 days
Title
Other adverse events
Time Frame
28 days
Title
Posttraumatic stress disorder / health-related quality of life
Time Frame
Hosptal discharge and 180 days after hospital discharge
Title
Immune response to hydrocortisone
Time Frame
6 days
Title
Adrenal function
Time Frame
baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Konrad Reinhart, MD
Organizational Affiliation
University Hospital Jena; Dept. of Anesthesiology an Intensive Care Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Didier Keh, MD
Organizational Affiliation
Charité Universitaetsmedizin Berlin, Dept. of Anesthsiology and Intensive Care Medicine
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Frank M Brunkhorst, MD
Organizational Affiliation
University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Markus Loeffler, MD
Organizational Affiliation
University Leipzig, Coordination Center of Clinical Studies (KKSL)
Official's Role
Study Director
Facility Information:
Facility Name
Universitaetsklinikum Aachen, Operative Intensivmedizin Erwachsene
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Zentralklinik Bad Berka GmbH, Zentrum für Anaesthesie, Intensivtherapie und Notfallmedizin
City
Bad Berka
ZIP/Postal Code
99437
Country
Germany
Facility Name
HELIOS Klinikum Bad Saarow; Zentrum für Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie
City
Bad Saarow
ZIP/Postal Code
15526
Country
Germany
Facility Name
St. Joseph Krankenhaus, Institut fue Anaesthesie, Schwerpunkt operative Intensivmedizin und SchmerztherapieAnaesthesie, operative Intensiv- und Notfallmedizin
City
Berlin
ZIP/Postal Code
12101
Country
Germany
Facility Name
Vivantes Auguste-Viktoria-Klinikum, Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie
City
Berlin
ZIP/Postal Code
12157
Country
Germany
Facility Name
Vivantes Klinikum Neukoelln,Klinik fuer Innere Medizin, Kardiologie und konservative Intensivmedizin
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Facility Name
Vivantes Klinikum-Neukoelln, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Facility Name
Vivantes Klinikum Hellersdorf, Klinik fuer Anaesthesie, operative Intensivmedizin und Schmerztherapie
City
Berlin
ZIP/Postal Code
12621
Country
Germany
Facility Name
Helios Klinikum Berlin Buch, Klinik für Intensivmedizin
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Campus Mitte, Med. Klinik mit Schwerpunkt Infektiologie und Pneumologie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum und Mitte Klinik für Anaesthesiologie und operative Intensivmedizin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Med. Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Vivantes Humboldt-Klinikum, Klinik für Innere Medizin - Kardiologie und konservative Intensivmedizin
City
Berlin
ZIP/Postal Code
13509
Country
Germany
Facility Name
Rheinische Friedrich-Wilhelms-Universitaet, Klinik für Anaesthesiologie und Operative Intensivmedizin
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Krankenhaus Dresden-Friedrichstadt, Klinik für Anaesthesiologie und Intensivmedizin
City
Dresden
ZIP/Postal Code
01067
Country
Germany
Facility Name
Universitaetsklinik Carl Gustav Carus Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Helios Klinikum Erfurt, Klinik fuer Anaesthesie, Intensivmedizin und Schmerztherapie
City
Erfurt
ZIP/Postal Code
99089
Country
Germany
Facility Name
Universitaetsklinikum Freiburg, Anaesthesiologische Universitaetsklinik - Abteilung Anaesthesiologie und Intensivtherapie
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Ernst Moritz Arndt Universitaet Greifswald, Klinik und Poliklinik für Anaesthesiologie und Intensivmedizin
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Medizinische Fakultaet der Martin-Luther-Universitaet Halle-Wittenberg - Universitaetsklinikum Halle (Saale)
City
Halle (Saale)
ZIP/Postal Code
06097
Country
Germany
Facility Name
Krankenhaus Martha-Maria Halle-Doelau GmbH
City
Halle (Saale)
ZIP/Postal Code
06120
Country
Germany
Facility Name
Universitaetsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Klinikum Heidenheim, Klinik für Anaesthesiologie und operative Intensivmedizin
City
Heidenheim
ZIP/Postal Code
89522
Country
Germany
Facility Name
Klinik Henningsdorf der Oberhavel-Kliniken GmbH, Abteilung für Anaesthesie und Intensivmedizin
City
Henningsdorf
ZIP/Postal Code
16716
Country
Germany
Facility Name
Friedrich Schiller Universität, Klinik für Anaesthesiologie und Intensivmedizin
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
Universitaetsklinikum Schleswig Holstein Campus Kiel, Klinik für Anaesthesiologie und Operative Intensivmedizin
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
St. Elisabeth-Krankenhaus Köln-Hohenlind, Klinik für Anaesthesiologie und operative Intensivmedizin
City
Koeln
ZIP/Postal Code
50935
Country
Germany
Facility Name
Kliniken der Stadt Koeln - Krankenhaus Merheim, Klinik für Anaesthesiologie und operative Intensivmedizin
City
Koeln
ZIP/Postal Code
51058
Country
Germany
Facility Name
Universitaetsklinikum Leipzig AöR, Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinikum Oldenburg GmbH, Klinik fuer Anaesthesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany

12. IPD Sharing Statement

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18158437
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Citation
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Results Reference
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PubMed Identifier
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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. doi: 10.1007/s00134-006-0517-7. Epub 2007 Feb 24.
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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.
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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.
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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.
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Citation
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Results Reference
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Links:
URL
http://www.sepsis-gesellschaft.de/DSG/Englisch/SepNet?sid=oKhUu07XmwBjbeKacHsxr0&iid=2
Description
Competence Network Sepsis (SepNet)

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Hydrocortisone for Prevention of Septic Shock

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