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Shock, SepticPhase 3CorticusNCT00147004

Corticosteroid Therapy of Septic Shock - Corticus

A Phase 3 study testing hydrocortisone sodium succinate in people with Shock, Septic, run by Hadassah Medical Organization at 57 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Shock, Septic
What is being tested?
hydrocortisone sodium succinate
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
500 participants
Where
57 sitesin 9 countries
Study dates
Mar 2002to Nov 2005
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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 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;
  • 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)].
  • Arterial hypoxemia (Pa02/FI02<280 in the absence of pneumonia)(Pa02/FI02<200 in the presence of pneumonia).
  • Thrombocytopenia - platelet count ≤ 100,000 cells/mm3.
  • Acute altered mental status (Glasgow Coma Scale < 14 or acute change from baseline).
  • 4. Informed Consent
  • 5. Cortisol level at baseline and 60 minutes after 0.25 mg cosyntropin

Who cannot join

  • 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.
  • Administration of chronic corticosteroids in the last 6 months or acute steroid therapy (any dose) within 4 weeks (including inhaled steroids). Topical steroids are not exclusions.
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  • 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.

Trial locations and contacts

57 sites in 9 countries.

57 sites in 9 countries

Germany24 sites

  • Zentralklinikum Augsburg

    Augsburg, D-86155

  • Vivantes-Klinikum im Friedrichshain

    Berlin, D - 10249

  • Vivantes-Klinikum Spandau

    Berlin, D - 13585

  • Evangelisches Waldkrankenhaus Spandau

    Berlin, D - 13589

  • Charité Campus Mitte

    Berlin, D-10117

  • St. Joseph Krankenhaus

    Berlin, D-12101

  • Charité - Campus Benjamin Franklin

    Berlin, D-12200

  • Vivantes-Klinikum Neukoelln

    Berlin, D-12313

  • Charité - Campus Charité Mitte

    Berlin, D-13353

  • Charité Campus Virchow -Klinikum

    Berlin, D-13353

  • Charité Campus Virchow-Klinikum

    Berlin, D-13353

  • Charité- Campus Virchow- Klinikum

    Berlin, D-13353

  • Institute for Anaesthesia and Operative Intensive Care

    Darmstadt, D-64283

  • University Hospital Dresden

    Dresden, D- 01307

  • Krankenhaus Hennigsdort

    Hennigsdorf, D-16761

  • Friedrich-Schiller Universitaet

    Jena, D - 07740

  • Klinikum Kemptern-Oberallegaeu

    Kempten, D-87439

  • Klinikum Landshut

    Landshut, D-84034

  • Klinikum Mannheim, University of Heidelberg

    Mannheim, D- 68167

  • Staedtisches Krankenhaus Muenchen-Harlaching

    München, D- 81545

  • Ludwig-Maximilian-Universitaet Muenchen

    München, D-81366

  • Klinikum Grosshadern, LMU Munich

    Munich, D-81377

  • Univesitaet Erlangen-Namberg

    Nuremberg, D-90471

  • Klinikum Ernst von Bergman

    Potsdam, D-14467

Other trials in Germany

United Kingdom8 sites

  • Aberdeen Royal Infirmary

    Aberdeen, AB25 2ZD

  • Southend Hospital

    Essex, SSO ORY

  • Ipswich Hospital

    Ipswich, IP4 5PD

  • Royal Lancaster Infirmary

    Lancaster, LA1 4RP

  • The General Infirmary at Leeds

    Leeds, LS1 3EX

  • Bloomsbury Institute of Intensive Care Medicine

    London, W1T 3AA

  • University of Manchester, Hope Hospital

    Salford, M6 8HD

  • Southampton General Hospital

    Southampton

Other trials in United Kingdom

France6 sites

  • Hopital de Caen

    Caen, 14033

  • Hopital Huriez

    Lille, F-59037

  • Hopital Caremeau

    Nîmes, 30029 cedex 9

  • Hopital Raymond Poincare

    Paris, Garches, F-92380

  • Hopital Lariboisiere

    Paris, Oarus, F-75010

  • Hopital Saint-Antoine

    Paris, F-75571

Other trials in France

Austria4 sites

  • LKH Feldkirch

    Feldkirch, A-6800

  • KH-BHS Linz

    Linz, A-4010

  • Krankenhaus der Barmherzigen Schwestern Ges. mbH

    Linz, A-4010

  • Universitaetsklinik fuer Innere Medizin II

    Vienna, A 1090

Other trials in Austria

Belgium4 sites

  • Hopital St. Joseph

    Arlon, B-6700

  • University Hospital Erasme

    Brussels, B-1070

  • Cliniques Universitaires St. Luc, UCL

    Brussels, B-1200

  • CHU Charleroi

    Charleroi, B-6000

Other trials in Belgium

Israel4 sites

  • Haemek Hospital

    Afula, 18101

  • Hadassah Medical Organisation

    Jerusalem, 91120

  • Beilinson Medical Centre

    Petah Tikva, 491000

  • Ichilov Hospital

    Tel Aviv, 64239

Other trials in Israel

Portugal3 sites

  • Hospital de St. Antonio do Capuchos

    Lisbon, 1150

  • UCIP, Hospital de Desterro

    Lisbon, 1150

  • Hospital de Egas Moniz

    Lisbon, 1349-019

Other trials in Portugal

Italy2 sites

  • Policlinico di Tor Vergata

    Roma, 00133

  • Centro di Rianimazione Ospedale S.Eugenio

    Roma, 00144

Other trials in Italy

Netherlands2 sites

  • Renier de Graaf Hospital

    Delft, 2600 GA

  • Erasmus University Medical Centre

    Rotterdam, 3000 CA

Other trials in Netherlands

About this study

Official title: Corticosteroid Therapy of Septic Shock - Corticus. A Multi-National, Prospective, Double-Blind, Randomized, Placebo-Controlled Study

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

Read the detailed description

The use of steroids in septic shock remains controversial. The purpose of this study is to determine whether hydrocortisone decreases 28-day mortality in patients with septic shock. The primary end point will be 28-day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH). Secondary endpoints will be 28 day all cause mortality in the total group and in responders, ICU and hospital mortality, one year mortality, organ system failure reversal especially shock, and duration of ICU and total hospitalisation.

In a double-blinded fashion (randomized on a 1:1 basis), patients receive 50 mg intravenously every 6 hours for 5 days. After 5 days, treatment will be tapered with 50 mg given intravenously every 12 hours for days 6-8, then 50 mg every 24 hours for days 9-11, and then stopped.

All concomitant treatments, including antibiotics, fluids, vasopressors and ancillary therapies will be given at the discretion of the primary care physician. Evidence-based guidelines for the management of severe sepsis and septic shock by the International Sepsis Forum (Intensive Care Med 2001;27:S124-S134) are encouraged to be followed.

All serious adverse events (SAE) which occur between days 0 and 28, which are unexpected and/or considered possibly or probably related to the study medication, must be documented and reported within 24 hours to the Safety and Efficacy Monitoring Committee. Non-serious adverse events will be listed on the case report form if they are unexpected and believed to be related to the study drug during days 0 to 14.

Specific adverse events which will be monitored closely because of their relationship to corticosteroids and shock are:

  1. Use of corticosteroids, i.e. gastrointestinal bleeding and superinfection; hyperglycemia, hypernatremia, muscular weakness, etc.
  2. Shock and use of vasopressors, i.e. stroke, acute myocardial infarction and peripheral ischemia.

In addition, substudies will include harmonization of cortisol by comparing cortisol levels measured in local laboratories and a central laboratory, immune and neuro-endocrine interactions, neuromuscular weakness and cytokines.

Conditions
Shock, Septic
Being tested
hydrocortisone sodium succinate, Placebo
Keywords
Septic shock, Steroids, Hydrocortisone, Mortality, Reversal of shock, Adrenal insufficiency
Medical subject headings
Shock, Septic, Adrenal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • hydrocortisone sodium succinateDrug

    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

  • PlaceboDrug

Study groups in NCT00147004
Study groupRoleWhat they receive
1Experimentalhydrocortisone sodium succinate
Receives: Drug: hydrocortisone sodium succinate
2Placebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 28 day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH)

    Measured: 28 days

Secondary outcomes (6)

  1. 28 day all cause mortality in the total group.

    Measured: 28 days

  2. 28 day all cause mortality in responders.

    Measured: 28 days

  3. One year mortality in nonresponders, total and responders.

    Measured: one year

  4. ICU and hospital mortality.

    Measured: one year

  5. Organ system failure reversal, especially shock.

    Measured: one year

  6. Duration of ICU and total hospitalisation.

    Measured: one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2005 (estimated)
  2. Study startMar 2002
  3. Primary completionNov 2005
  4. Study completionNov 2005

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
500 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00147004
Sponsor's protocol ID
QLK2-CT-2000-00589
Other IDs
EC- QLK2-CT-2000-00589
Acronym
Corticus
Status last verified
Apr 2008
First submitted
6 Sep 2005
Last updated
24 Apr 2008
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 12761380

  • 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.

    PubMed 18184957

  • 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.

    PubMed 22073145

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing hydrocortisone sodium succinate in people with Shock, Septic, run by Hadassah Medical Organization at 57 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in Germany, United Kingdom, France, Austria, Belgium and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

28 day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH) (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00147004, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2008.

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