NCT00147004

Brief Summary

The purpose of the study is to determine whether steroids decrease 28-day mortality in patients with septic shock.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
500

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Mar 2002

Typical duration for phase_3

Geographic Reach
9 countries

57 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2002

Completed
3.5 years until next milestone

First Submitted

Initial submission to the registry

September 6, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 7, 2005

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2005

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2005

Completed
Last Updated

April 24, 2008

Status Verified

April 1, 2008

Enrollment Period

3.7 years

First QC Date

September 6, 2005

Last Update Submit

April 23, 2008

Conditions

Keywords

Septic shockSteroidsHydrocortisoneMortalityReversal of shockAdrenal insufficiency

Outcome Measures

Primary Outcomes (1)

  • 28 day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH)

    28 days

Secondary Outcomes (6)

  • 28 day all cause mortality in the total group.

    28 days

  • 28 day all cause mortality in responders.

    28 days

  • One year mortality in nonresponders, total and responders.

    one year

  • ICU and hospital mortality.

    one year

  • Organ system failure reversal, especially shock.

    one year

  • +1 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL

hydrocortisone sodium succinate

Drug: hydrocortisone sodium succinate

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

50 mg intravenous bolus every six hours for 5 days, then tapered to 50 mg intravenously every 12 hours for days 6-8, 50 mg every 24 hours for days 9-11 and then stopped

1
2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Clinical evidence of infection within the previous 72 hours (may be present longer than 72 hours) (a, b, c, or d - only 1 required)
  • Presence of polymorphonuclear cells in a normally sterile body fluid (excluding blood);
  • Culture or Gram stain of blood, sputum, urine or normally sterile body fluid positive for a pathogenic micro-organism;
  • Focus of infection identified by visual inspection (e.g. ruptured bowel with the presence of free air or bowel contents in the abdomen found at the time of surgery, wound with purulent drainage);
  • Other clinical evidence of infection - treated community acquired pneumonia, purpura fulminans, necrotising fascitis, etc.
  • Evidence of a systemic response to infection as defined by the presence of two or more of the following signs within the previous 24 hours. These signs may be present longer than 72 hours.
  • Fever (temperature \>38.3°C) or hypothermia (rectal temperature \< 35.6°C);
  • Tachycardia (heart rate of \>90 beat/min);
  • Tachypnea (respiratory rate \> 20 breaths/min, PaC02\<32 mmHg) or patient requires invasive mechanical ventilation;
  • Alteration of the WBC count \>12,000 cells/mm3, \<4,000 cells/mm3 or \>10% immature neutrophils (bands).
  • Evidence of shock defined by (A + B- both required within the previous 72 hours (may NOT be present longer than 72 hours).
  • A. A systolic blood pressure \< 90 mmHg or a decrease in SBP of more than 50 mmHg from baseline in previous hypertensive patients (for at least one hour) despite adequate fluid replacement OR need for vasopressors for at least one hour (infusion of dopamine ≥ 5 mcg/kg/min or any dose of adrenaline, noradrenaline, phenylephrine or vasopressin) to maintain a SBP ≥ 90 mmHg;
  • B. Hypoperfusion or organ dysfunction which is not the result of underlying diseases or drugs, but is attributable to sepsis, including one of the following:
  • Sustained oliguria (urine output \< 0.5 ml/kg/hr for a minimum of 1 hour)
  • Metabolic acidosis \[pH of \< 7.3, or a base deficit of \> or = 5.0 mmol/L, or an increased lactic acid concentration (\> 2 mmol/L)\].
  • +5 more criteria

You may not qualify if:

  • Pregnancy
  • Age less than 18.
  • Underlying disease with a prognosis for survival of less than 3 months.
  • Cardiopulmonary resuscitation within 72 hours before study.
  • Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4 weeks before the study.
  • HIV positivity.
  • Presence of an advanced directive to withhold or withdraw life sustaining treatment (i.e. DNR).
  • Advanced cancer with a life expectancy less than 3 months.
  • Acute myocardial infarction or pulmonary embolus.
  • Another experimental drug study within the last 30 days.
  • Moribund patients likely to die within 24 hours.
  • Patients in the ICU for more than 2 months at the time of the start of septic shock.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (57)

LKH Feldkirch

Feldkirch, A-6800, Austria

Location

KH-BHS Linz

Linz, A-4010, Austria

Location

Krankenhaus der Barmherzigen Schwestern Ges. mbH

Linz, A-4010, Austria

Location

Universitaetsklinik fuer Innere Medizin II

Vienna, A 1090, Austria

Location

Hopital St. Joseph

Arlon, B-6700, Belgium

Location

University Hospital Erasme

Brussels, B-1070, Belgium

Location

Cliniques Universitaires St. Luc, UCL

Brussels, B-1200, Belgium

Location

CHU Charleroi

Charleroi, B-6000, Belgium

Location

Hopital Raymond Poincare

Paris, Garches, F-92380, France

Location

Hopital Lariboisiere

Paris, Oarus, F-75010, France

Location

Hopital de Caen

Caen, 14033, France

Location

Hopital Huriez

Lille, F-59037, France

Location

Hopital Caremeau

Nîmes, 30029 cedex 9, France

Location

Hopital Saint-Antoine

Paris, F-75571, France

Location

Zentralklinikum Augsburg

Augsburg, D-86155, Germany

Location

Vivantes-Klinikum im Friedrichshain

Berlin, D - 10249, Germany

Location

Vivantes-Klinikum Spandau

Berlin, D - 13585, Germany

Location

Evangelisches Waldkrankenhaus Spandau

Berlin, D - 13589, Germany

Location

Charité Campus Mitte

Berlin, D-10117, Germany

Location

St. Joseph Krankenhaus

Berlin, D-12101, Germany

Location

Charité - Campus Benjamin Franklin

Berlin, D-12200, Germany

Location

Vivantes-Klinikum Neukoelln

Berlin, D-12313, Germany

Location

Charité - Campus Charité Mitte

Berlin, D-13353, Germany

Location

Charité Campus Virchow -Klinikum

Berlin, D-13353, Germany

Location

Charité Campus Virchow-Klinikum

Berlin, D-13353, Germany

Location

Charité- Campus Virchow- Klinikum

Berlin, D-13353, Germany

Location

Institute for Anaesthesia and Operative Intensive Care

Darmstadt, D-64283, Germany

Location

University Hospital Dresden

Dresden, D- 01307, Germany

Location

Krankenhaus Hennigsdort

Hennigsdorf, D-16761, Germany

Location

Friedrich-Schiller Universitaet

Jena, D - 07740, Germany

Location

Klinikum Kemptern-Oberallegaeu

Kempten, D-87439, Germany

Location

Klinikum Landshut

Landshut, D-84034, Germany

Location

Klinikum Mannheim, University of Heidelberg

Mannheim, D- 68167, Germany

Location

Klinikum Grosshadern, LMU Munich

Munich, D-81377, Germany

Location

Staedtisches Krankenhaus Muenchen-Harlaching

München, D- 81545, Germany

Location

Ludwig-Maximilian-Universitaet Muenchen

München, D-81366, Germany

Location

Univesitaet Erlangen-Namberg

Nuremberg, D-90471, Germany

Location

Klinikum Ernst von Bergman

Potsdam, D-14467, Germany

Location

Haemek Hospital

Afula, 18101, Israel

Location

Hadassah Medical Organisation

Jerusalem, 91120, Israel

Location

Beilinson Medical Centre

Petah Tikva, 491000, Israel

Location

Ichilov Hospital

Tel Aviv, 64239, Israel

Location

Policlinico di Tor Vergata

Roma, 00133, Italy

Location

Centro di Rianimazione Ospedale S.Eugenio

Roma, 00144, Italy

Location

Renier de Graaf Hospital

Delft, 2600 GA, Netherlands

Location

Erasmus University Medical Centre

Rotterdam, 3000 CA, Netherlands

Location

Hospital de St. Antonio do Capuchos

Lisbon, 1150, Portugal

Location

UCIP, Hospital de Desterro

Lisbon, 1150, Portugal

Location

Hospital de Egas Moniz

Lisbon, 1349-019, Portugal

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZD, United Kingdom

Location

Southend Hospital

Essex, SSO ORY, United Kingdom

Location

Ipswich Hospital

Ipswich, IP4 5PD, United Kingdom

Location

Royal Lancaster Infirmary

Lancaster, LA1 4RP, United Kingdom

Location

The General Infirmary at Leeds

Leeds, LS1 3EX, United Kingdom

Location

Bloomsbury Institute of Intensive Care Medicine

London, W1T 3AA, United Kingdom

Location

University of Manchester, Hope Hospital

Salford, M6 8HD, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (3)

  • Annane D, Briegel J, Sprung CL. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003 May 22;348(21):2157-9. doi: 10.1056/NEJM200305223482123. No abstract available.

    PMID: 12761380BACKGROUND
  • 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.

  • Polito A, Sonneville R, Guidoux C, Barrett L, Viltart O, Mattot V, Siami S, Lorin de la Grandmaison G, Chretien F, Singer M, Gray F, Annane D, Brouland JP, Sharshar T. Changes in CRH and ACTH synthesis during experimental and human septic shock. PLoS One. 2011;6(11):e25905. doi: 10.1371/journal.pone.0025905. Epub 2011 Nov 3.

MeSH Terms

Conditions

Shock, SepticAdrenal Insufficiency

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

SepsisInfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShockAdrenal Gland DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

PregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-Hydroxycorticosteroids

Study Officials

  • Charles L Sprung, MD

    Hadasah Medical Organization

    STUDY CHAIR
  • Djillali Annane, MD

    Hopital Raymond Poincare

    STUDY DIRECTOR
  • Josef Briegel, MD

    Ludwig-Maximilian-Universitaet Muenchen

    STUDY DIRECTOR
  • Didier Keh, MD

    Charite Campus Virchow-Klinikum

    STUDY DIRECTOR
  • Rui Moreno, MD

    Hospital de St. António dos Capuchos

    STUDY DIRECTOR
  • Didier Pittet, MD

    University Hospital, Geneva

    STUDY DIRECTOR
  • Mervyn Singer, MD

    University College, London

    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

Study Record Dates

First Submitted

September 6, 2005

First Posted

September 7, 2005

Study Start

March 1, 2002

Primary Completion

November 1, 2005

Study Completion

November 1, 2005

Last Updated

April 24, 2008

Record last verified: 2008-04

Locations