ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock (ADRENAL)

This study is currently recruiting participants.
Verified April 2014 by The George Institute
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Information provided by (Responsible Party):
The George Institute
ClinicalTrials.gov Identifier:
NCT01448109
First received: October 5, 2011
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to find out whether adult patients admitted to the Intensive Care Unit with septic shock who are given hydrocortisone compared to placebo (a dummy solution), will have an improved rate of survival 90 days later.

Septic shock is the result of an infection, which triggers a complex response by the body (the inflammatory response) that causes a decrease in blood pressure and subsequently one or more organ systems to fail when blood supply to these organs is reduced. This may result in poor recovery and death. About a quarter of the people who suffer septic shock that is not rapidly reversed, will die.

When patients are admitted to Intensive Care with sepsis and/or septic shock they receive a number of therapies. These include fluids given through a drip, antibiotics, drugs to boost your blood pressure and other organ systems.

In addition to these therapies, steroids (hydrocortisone) are sometimes administered. Whether steroids are useful or not in the treatment of severe infections has been studied for more than 50 years. Previous research has suggested that the use of low dose steroid may have shortterm benefits in improving the circulation. However, there is no agreement amongst doctors around the world about whether treatment with or without low dose steroids improves the overall recovery and survival in patients with septic shock. This study would allow doctors to make informed decisions about whether the addition of low dose steroid therapy is better for patients with septic shock in intensive care.

The study will include 3800 intensive care patients who have septic shock. Each enrolled patient will be randomised to receive either Hydrocortisone 200mg or placebo daily for 7 days as a continuous intravenous infusion while in intensive care. The patient will be followed for 90 days. If the patient is discharged prior to 90 days a telephone call will be made for the followup information. At six months the patient will be contacted again for completion of a quality of life questionnaire.


Condition Intervention Phase
Septic Shock
Drug: Hydrocortisone
Drug: Sterile air filled vial
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Blinded Placebo Controlled Trial of Hydrocortisone in Critically Ill Patients With Septic Shock

Resource links provided by NLM:


Further study details as provided by The George Institute:

Primary Outcome Measures:
  • All cause mortality at 90 days after randomisation [ Time Frame: 90 days after randomisation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All-cause mortality at 28 days and 6 months after randomisation [ Time Frame: 28 days and 6 months after randomisation ] [ Designated as safety issue: No ]
  • Time to resolution of shock [ Time Frame: MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation. ] [ Designated as safety issue: No ]
    Time to resolution of shock - defined as "the time taken to achieve a clinician prescribed mean arterial pressure (MAP) goal for >24 hours without vasopressors or inotropes.

  • Recurrence of shock [ Time Frame: Up to90 days after randomisation ] [ Designated as safety issue: No ]
    Recurrence of shock - defined as a new episode of shock after reversal of the initial episode.

  • Duration of ICU stay [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Duration of hospital stay [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Frequency and duration of mechanical ventilation [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Duration of renal replacement therapy [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Development of bacteraemia [ Time Frame: 2 and 14 days post randomisation ] [ Designated as safety issue: No ]
  • Bleeding requiring blood transfusions received in the ICU [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Quality of Life assessment at 6 months. [ Time Frame: 6 months. ] [ Designated as safety issue: No ]

Estimated Enrollment: 3800
Study Start Date: June 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hydrocortisone Drug: Hydrocortisone
Hydrocortisone 100mg vial (blinded) is reconstituted with 2ml of water for Injection, agitated for 20 seconds, rested for 3 minutes, contents of vial aspirated and added to 100ml bag of normal saline or 5% dextrose and given intravenously as a continuous infusion at rate of 200mg/per day for 7 days.
Other Name: Solucortef
Placebo Comparator: Sterile air filled vial Drug: Sterile air filled vial
the "sterile air filled vial" (blinded) is reconstituted with 2ml of water for Injection, agitated for 20 seconds, rested for 3 minutes, contents of vial aspirated and added to 100ml bag of normal saline or 5% dextrose and given intravenously as a continuous infusion. 2 sterile air filled vials per day for 7 days

Detailed Description:

Primary Objective To evaluate the impact of intravenous hydrocortisone versus placebo on all cause mortality at 90 days in critically ill patients with septic shock. The hypothesis is that hydrocortisone, compared to placebo, reduces 90-day all-cause mortality in patients admitted to an ICU with septic shock. 'Shock' is defined as the need for vasopressors or inotropes to maintain a systolic blood pressure > 90 millimetres of mercury (mmHg), or mean arterial blood pressure > 60mmHg or a mean arterial pressure (MAP) target set by the treating clinician for maintaining perfusion. 'Septic shock' is shock that is secondary to sepsis

Secondary Objectives To assess the impact of intravenous hydrocortisone versus placebo on the recovery from, and the complications of, septic shock and the development of treatment related adverse reactions.

Study Design This study is a multi centre, randomised, blinded, placebo controlled trial comparing intravenous hydrocortisone with placebo in critically ill patients with septic shock.

Randomisation will be achieved via a secure interactive web based system using permuted block minimisation. Randomisation will be stratified by participating site and by operative or non-operative admission to the ICU.

The primary endpoint for this trial will be death from all causes at 90 days.

Pre defined sub groups will include the following categories:

  • Operative (admitted to ICU from operating theatre or recovery room) versus non-operative admission.
  • Dose of adrenaline or noradrenaline at randomisation - ≤ 15 mcg / minute versus > 15 mcg / minute.

3,800 patients will be enrolled in this study at approximately 50 - 60 study sites. Eligible patients will be randomised to receive either intravenous hydrocortisone 200mg or placebo per day for 7 days.

For all patients, data will be collected at baseline and then daily whilst the patient is in the ICU. Patients will be followed up to day 14, regardless of where the patient resides in the hospital, to monitor the development of bacteraemia. Additional follow up will occur at 90 days and at 6 months post randomisation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18 years or older
  2. Documented site of infection, or strong suspicion of infection, with 2 of the 4 clinical signs of inflammation:

    • Core temperature > 38°C or < 35°C
    • Heart rate > 90 beats per minute
    • White cell count > 12 x 109/L or < 4 x 109/L or > 10% immature neutrophils
    • Respiratory rate > 20 breaths per minute, or PaCO2 < 32 mmHg, or mechanical ventilation.
  3. Being treated with mechanical ventilation at the time of randomisation
  4. Being treated with vasopressors or inotropes to maintain a systolic blood pressure > 90mmHg, or mean arterial blood pressure > 60mmHg, or a MAP target set by the treating clinician for maintaining perfusion
  5. Administration of vasopressors or inotropes for = 4 hours and present at time of randomisation.

Exclusion Criteria:

  1. Met all inclusion criteria more than 24 hours ago
  2. Clinician expects to prescribe systemic corticosteroids for an indication other than septic shock (not including nebulised or inhaled corticosteroid)
  3. Patients treated with etomidate
  4. Patients receiving treatment with Amphotericin B for systemic fungal infections at time of randomisation
  5. Patients with documented cerebral malaria at the time of randomisation
  6. Patients with documented strongyloides infection at the time of randomisation
  7. Death is deemed inevitable or imminent during this admission and either the attending physician, patient or surrogate legal decision maker is not committed to active treatment
  8. Death from underlying disease is likely within 90 days
  9. Patient has been previously enrolled in the ADRENAL study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01448109

Contacts
Contact: Dorrilyn Rajbhandari +61 410 442 828 drajbhandari@georgeinstitute.org.au

  Hide Study Locations
Locations
Australia, New South Wales
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Dr Graham Reece, Dr       graham_reece@wsahs.nsw.gov.au   
Contact: Dr Dhaval Ghelani       dhaval.ghelani@wsahs.nsw.gov.au   
Principal Investigator: Dr Graham Reece         
Sub-Investigator: Dr Dhaval Ghelani         
Royal Prince Alfred Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Dr Heike Koelzow       Heike.Koelzow@sswahs.nsw.gov.au   
Contact: Dr David Gattas       dgattas@med.usyd.edu.au   
Principal Investigator: Dr Heike Koelzow         
Sub-Investigator: Dr David Gattas         
St Vincent's Hospital Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Dr Priya Nair       pnair@stvincents.com.au   
Principal Investigator: Dr Priya Nair, pnair@stvincents.com.au         
St George Hospital Recruiting
Kogarah, New South Wales, Australia, 2217
Contact: Dr Manoj Saxena       Manoj.Saxena@sesiahs.health.nsw.gov.au   
Principal Investigator: Dr Manoj Saxena         
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 1871
Contact: A/Prof Anders Aneman       anders.aneman@sswahs.nsw.gov.au   
Contact: Dr Anthony Stewart       anthony.stewart@sswahs.health.nsw.gov.au   
Principal Investigator: Dr Anders Aneman         
Principal Investigator: Dr Anthony Stewart         
Sub-Investigator: Dr William O'Regan         
John Hunter Hospital Recruiting
Newcastle, New South Wales, Australia, 2305
Contact: Dr Peter Harrigan       peter.harrigan@hnehealth.nsw.gov.au   
Principal Investigator: Dr Peter Harrigan         
Nepean Hospital Recruiting
Penrith, New South Wales, Australia, 2747
Contact: Dr Ian Seppelt       seppelt@med.usyd.edu.au   
Contact: Dr Louise Cole       louise.cole@sydney.edu.au   
Principal Investigator: Dr Ian Seppelt         
Sub-Investigator: Dr Louise Cole         
Prince of Wales Hospital Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Prof Yahya Shehabi       y.shehabi@unsw.edu.au   
Contact: Sumesh Arora       Sumesh.Arora@SESIAHS.HEALTH.NSW.GOV.AU   
Principal Investigator: Prof Yahya Shehabi         
Sub-Investigator: Sumesh Arora         
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2065
Contact: Dr Anthony Delaney       adelaney@med.usyd.edu.au   
Principal Investigator: Dr Anthony Delaney         
The George Institute for Global Health Not yet recruiting
Sydney, New South Wales, Australia, 2000
Contact: Dorrilyn Rajbhandari    +61 410 442 828    drajbhandari@georgeinstitute.org.au   
Tamworth Rural Referral Hospital Recruiting
Tamworth, New South Wales, Australia, 2340
Contact: Dr Peter May       peter.may@hnehealth.nsw.gov.au   
Contact: Dr Chris Trethewy       Christopher.Trethewy@hnehealth.nsw.gov.au   
Principal Investigator: Dr Peter May         
Sub-Investigator: Dr Chris Trethewy         
Calvary Mater Hospital (Newcastle) Recruiting
Waratah, New South Wales, Australia, 2298
Contact: Dr Katrina Ellem       katrina.ellem@calvarymater.org.au   
Principal Investigator: Dr Katrina Ellem         
Wollongong Hospital Recruiting
Wollongong, New South Wales, Australia, 2521
Contact: Dr Martin Sterba       martin.sterba@sesiahs.health.nsw.gov.au   
Contact: Dr Michael Davis       michaeljohndavis.davis@sesiahs.health.nsw.gov.au   
Principal Investigator: Dr Martin Sterba         
Sub-Investigator: Dr Michael Davis         
Australia, Northern Territory
Darwin Hospital Recruiting
Darwin, Northern Territory, Australia, 0810
Contact: Dr Dianne Stephens       dianne.stephens@nt.gov.au   
Contact: Dr Sidarth Agarwal       sidarth.agarwal@nt.gov.au   
Principal Investigator: Dr Dianne Stephens         
Sub-Investigator: Dr Sidathr Agarwal         
Australia, Queensland
Wesley Hospital Recruiting
Auchenflower, Queensland, Australia, 4066
Contact: Bala Venkatesh       bvenkatesh@georgeinstitute.org.au   
Principal Investigator: Bala Venkatesh         
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4029
Contact: Dr Jeremy Cohen       Jeremy_Cohen@health.qld.gov.au   
Principal Investigator: Dr Jeremy Cohen         
Ipswich Hospital Recruiting
Ipswich, Queensland, Australia, 4307
Contact: Dr Anand Krishnan       anand_krishnan@health.qld.gov.au   
Contact: Dr Nandan Bhende       nandan_bhende@health.qld.gov.au   
Principal Investigator: Dr Anand Krishnan         
Sub-Investigator: Dr Nandan Bhende         
Sub-Investigator: Dr Judith Ochola         
Logan Hospital Recruiting
Logan, Queensland, Australia, 4131
Contact: Dr Hayden White       Hayden_White@health.qld.gov.au   
Principal Investigator: Dr Hayden White         
Nambour Hospital Recruiting
Nambour, Queensland, Australia, 4560
Contact: Peter Garrett       peter_garrett@health.qld.gov.au   
Principal Investigator: Peter Garrett         
Redcliffe Hospital Recruiting
Redcliffe, Queensland, Australia, 4020
Contact: Tim Warhurst       tim_warhurst@health.qld.gov.au   
Principal Investigator: Tim Warhurst         
Mater Health Services Withdrawn
South Brisbane, Queensland, Australia, 4101
Toowoomba Hospital Recruiting
Toowoomba, Queensland, Australia, 4350
Contact: Vasanth Mariappa       vasanth_mariappa@health.qld.gov.au   
Principal Investigator: Vasanth Mariappa         
Princess Alexandra Hospital Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Prof Bala Venkatesh       bvenkatesh@georgeinstitute.org.au   
Contact: A/Prof Chris Joyce       chris.joyce@health.qld.gov.au   
Principal Investigator: Prof Bala Venkatesh         
Sub-Investigator: A/Prof Chris Joyce         
Australia, South Australia
Lyell McEwin Hospital Recruiting
Elizabeth Vale, South Australia, Australia, 5112
Contact: Peter Thomas       peter.thomas2@health.sa.gov.au   
Principal Investigator: Peter Thomas         
The Queen Elizabeth Hospital Recruiting
Woodville South, South Australia, Australia, 5011
Principal Investigator: Sandra Peake, MBBS         
Australia, Tasmania
Royal Hobart Hospital Recruiting
Hobart, Tasmania, Australia, 7000
Contact: David Cooper       david.cooper@dhhs.tas.gov.au   
Principal Investigator: David Cooper         
Australia, Victoria
Bendigo Hospital Recruiting
Bendigo, Victoria, Australia, 3550
Contact: Jason Fletcher       jfletcher@bendigohealth.org.au   
Principal Investigator: Jason Fletcher         
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Contact: Sanjiv Vij       vijsanjiv@gmail.com   
Principal Investigator: Sanjiv Vij         
Dandenong Hospital Withdrawn
Dandenong, Victoria, Australia, 3175
Northern Hospital Recruiting
Epping, Victoria, Australia, 3076
Contact: Angaj Ghosh       angaj.ghosh@nh.org.au   
Principal Investigator: Angaj Ghosh         
St Vincent's Hospital (Melbourne) Recruiting
Fitzroy, Victoria, Australia, 3065
Contact: Antony Tobin       antony.tobin@svhm.org.au   
Principal Investigator: Antony Tobin         
Western Hospital Recruiting
Footscray, Victoria, Australia, 3011
Contact: Craig French       craig.french@wh.org.au   
Principal Investigator: Craig French         
Geelong Hospital (Barwon Health) Recruiting
Geelong, Victoria, Australia, 3220
Contact: Martina Chonghaile       mnicho@barwonhealth.com.au   
Principal Investigator: Martina Chonghaile         
Sub-Investigator: Neil Orford         
Austin Hospital Recruiting
Heidelburg, Victoria, Australia, 3084
Contact: Rinaldo Bellomo       rbellomo@georgeinstitute.org.au   
Principal Investigator: Rinaldo Bellomo         
Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Contact: Christopher MacIsaac       christopher.macisaac@mh.org.au   
Principal Investigator: Christopher MacIsaac         
Australia, Western Australia
Fremantle Hospital Recruiting
Fremantle, Western Australia, Australia, 6959
Contact: Bart De Keulenaer       bart.dekeulenaer@health.wa.gov.au   
Principal Investigator: Bart De Keulenaer         
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Contact: Edward Litton       edward.litton@health.wa.gov.au   
Principal Investigator: Edward Litton         
New Zealand
Waikato Hospital Recruiting
Hamilton, NZ, New Zealand, 3240
Contact: Dr Tom O'Rourke         
Principal Investigator: Dr Tom O'Rourke         
Auckland City Hospital (DCCM) Recruiting
Auckland, New Zealand, 1142
Contact: Dr Colin Macarthur       ColinM@adhb.govt.nz   
Principal Investigator: Dr Colin Macarthur         
Auckland City Hospital (CVICU) Not yet recruiting
Auckland, New Zealand, 1142
Contact: Dr Shay McGuinness       shaymc@adhb.govt.nz   
Principal Investigator: Dr Shay McGuinness         
Middlemore Hospital Recruiting
Auckland, New Zealand, 1640
Contact: Dr Alex Kazemi       Alex.Kazemi@middlemore.co.nz   
Contact: Dr Tony Williams       tony.williams@cmdhb.org.nz   
Principal Investigator: Dr Alex Kazemi         
Sub-Investigator: Dr Tony Williams         
Christchurch Hospital Recruiting
Christchurch, New Zealand, 8011
Contact: Dr Seton Henderson       seton.henderson@cdhb.govt.nz   
Contact: Dr David Knight       david.knight@cdhb.govt.nz   
Principal Investigator: Dr Seton Henderson         
Sub-Investigator: Dr David Knight         
Tauranga Hospital Recruiting
Tauranga, New Zealand, 3110
Contact: Dr Troy Browne       Troy.Browne@bopdhb.govt.nz   
Principal Investigator: Dr Troy Browne         
Wellington Hospital Recruiting
Wellington, New Zealand, 6011
Contact: Dr Paul Young       paul.young@ccdhb.org.nz   
Contact: Dr Richard Dinsdale       dick.dinsdale@ccdhb.org.nz   
Principal Investigator: Dr Paul Young         
Sub-Investigator: Dr Richard Dinsdale         
Sponsors and Collaborators
The George Institute
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Investigators
Study Chair: Balasubramanian Venkatesh The George Institute
  More Information

No publications provided

Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT01448109     History of Changes
Other Study ID Numbers: GI-CCT372273
Study First Received: October 5, 2011
Last Updated: April 9, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The George Institute:
Sepsis
Corticosteroid

Additional relevant MeSH terms:
Critical Illness
Shock
Shock, Septic
Disease Attributes
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on April 22, 2014