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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by The George Institute
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 Identifier:
First received: October 5, 2011
Last updated: October 17, 2016
Last verified: March 2016

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
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 ]

Secondary Outcome Measures:
  • All-cause mortality at 28 days and 6 months after randomisation [ Time Frame: 28 days and 6 months after randomisation ]
  • Time to resolution of shock [ Time Frame: MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation. ]
    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 ]
    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 ]
  • Duration of hospital stay [ Time Frame: Up to 90 days after randomisation ]
  • Frequency and duration of mechanical ventilation [ Time Frame: Up to 90 days after randomisation ]
  • Duration of renal replacement therapy [ Time Frame: Up to 90 days after randomisation ]
  • Development of bacteraemia [ Time Frame: 2 and 14 days post randomisation ]
  • Bleeding requiring blood transfusions received in the ICU [ Time Frame: Up to 90 days after randomisation ]
  • Quality of Life assessment at 6 months. [ Time Frame: 6 months. ]

Estimated Enrollment: 3800
Study Start Date: June 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: December 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01448109

Contact: Dorrilyn Rajbhandari +61 410 442 828

  Hide Study Locations
Australia, New South Wales
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Graham Reece, Dr   
Contact: Dhaval Ghelani   
Principal Investigator: Graham Reece         
Sub-Investigator: Dhaval Ghelani         
Royal Prince Alfred Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Heike Koelzow   
Contact: David Gattas   
Principal Investigator: Heike Koelzow         
Sub-Investigator: David Gattas         
St Vincent's Hospital Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Priya Nair   
Principal Investigator: Priya Nair,         
Gosford Hospital Recruiting
Gosford, New South Wales, Australia, 2250
Contact: Atul Gaur       Atul Gaur <>   
Contact: Rob Cameron   
St George Hospital Recruiting
Kogarah, New South Wales, Australia, 2217
Contact: Manoj Saxena   
Principal Investigator: Manoj Saxena         
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 1871
Contact: Anders Aneman   
Contact: Anthony Stewart   
Principal Investigator: Anders Aneman         
Principal Investigator: Anthony Stewart         
John Hunter Hospital Recruiting
Newcastle, New South Wales, Australia, 2305
Contact: Peter Harrigan   
Principal Investigator: Peter Harrigan         
Nepean Hospital Recruiting
Penrith, New South Wales, Australia, 2747
Contact: Ian Seppelt   
Contact: Louise Cole   
Principal Investigator: Ian Seppelt         
Sub-Investigator: Louise Cole         
Prince of Wales Hospital Active, not recruiting
Randwick, New South Wales, Australia, 2031
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2065
Contact: Anthony Delaney   
Principal Investigator: Anthony Delaney         
The George Institute for Global Health Active, not recruiting
Sydney, New South Wales, Australia, 2000
Tamworth Rural Referral Hospital Recruiting
Tamworth, New South Wales, Australia, 2340
Contact: Vinodh Madapusi   
Contact: Viji Rao   
Principal Investigator: Vinodh Madapusi         
Principal Investigator: Viji Rao         
Tweed Heads District Hospital Recruiting
Tweeds Head, New South Wales, Australia, 2485
Contact: Joe Ogg   
Principal Investigator: Joe Ogg         
Calvary Mater Hospital (Newcastle) Recruiting
Waratah, New South Wales, Australia, 2298
Contact: Katrina Ellem   
Principal Investigator: Katrina Ellem         
Wollongong Hospital Recruiting
Wollongong, New South Wales, Australia, 2521
Contact: Martin Sterba   
Contact: Michael Davis   
Principal Investigator: Martin Sterba         
Sub-Investigator: Michael Davis         
Australia, Northern Territory
Royal Darwin Hospital Recruiting
Darwin, Northern Territory, Australia, 0810
Contact: Dianne Stephens   
Contact: Sidarth Agarwal   
Principal Investigator: Dianne Stephens         
Sub-Investigator: Sidathr Agarwal         
Australia, Queensland
Wesley Hospital Recruiting
Auchenflower, Queensland, Australia, 4066
Contact: Bala Venkatesh   
Principal Investigator: Bala Venkatesh         
Prince Charles Hospital Recruiting
Brisbane, Queensland, Australia, 4032
Contact: Marc Ziegenfuss   
Principal Investigator: Marc Ziegenfuss         
Sub-Investigator: John Fraser         
Mater Health Services Recruiting
Brisbane, Queensland, Australia, 4101
Contact: Jeffery Presneill   
Contact: David Sturgess   
Principal Investigator: Jeffery Presneill         
Sub-Investigator: David Sturgess         
Gold Coast University Hospital Recruiting
Gold Coast, Queensland, Australia, 4215
Contact: James Winearls   
Principal Investigator: James Winearls         
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4029
Contact: Jeremy Cohen   
Principal Investigator: Jeremy Cohen         
Ipswich Hospital Recruiting
Ipswich, Queensland, Australia, 4307
Contact: Anand Krishnan   
Contact: Nandan Bhende   
Principal Investigator: Anand Krishnan         
Sub-Investigator: Nandan Bhende         
Logan Hospital Recruiting
Logan, Queensland, Australia, 4131
Contact: Hayden White   
Principal Investigator: Hayden White         
Mackay Base Hospital Recruiting
Mackay, Queensland, Australia, 4740
Contact: Neeraj Bhadange   
Principal Investigator: Neeraj Bhadange         
Nambour Hospital Recruiting
Nambour, Queensland, Australia, 4560
Contact: John Moore   
Contact: Victoria Campbell   
Principal Investigator: John Moore         
Sub-Investigator: Victoria Campbell         
Redcliffe Hospital Recruiting
Redcliffe, Queensland, Australia, 4020
Contact: Tim Warhurst   
Contact: Hamish Pollock   
Principal Investigator: Tim Warhurst         
Sub-Investigator: Hamish Pollock         
Toowoomba Hospital Recruiting
Toowoomba, Queensland, Australia, 4350
Contact: Vasanth Mariappa   
Principal Investigator: Vasanth Mariappa         
Townsville Hospital Recruiting
Townsville, Queensland, Australia, 4814
Contact: Siva Senthuran   
Principal Investigator: Siva Senthuran         
Princess Alexandra Hospital Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Bala Venkatesh   
Contact: Chris Joyce   
Principal Investigator: Bala Venkatesh         
Sub-Investigator: Chris Joyce         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Marianne Chapman   
Principal Investigator: Marianne Chapman         
Lyell McEwin Hospital Recruiting
Elizabeth Vale, South Australia, Australia, 5112
Contact: Peter Thomas   
Principal Investigator: Peter Thomas         
The Queen Elizabeth Hospital Recruiting
Woodville South, South Australia, Australia, 5011
Contact: Sandra Peake   
Principal Investigator: Sandra Peake, MBBS         
Australia, Tasmania
Royal Hobart Hospital Recruiting
Hobart, Tasmania, Australia, 7000
Contact: David Cooper   
Contact: Umesh Kadam   
Principal Investigator: David Cooper         
Sub-Investigator: Umesh Kadam         
Australia, Victoria
Bendigo Hospital Recruiting
Bendigo, Victoria, Australia, 3550
Contact: Jason Fletcher   
Contact: John Edington   
Principal Investigator: Jason Fletcher         
Sub-Investigator: John Edington         
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Contact: Tim Crozier   
Principal Investigator: Tim Crozier         
Dandenong Hospital Withdrawn
Dandenong, Victoria, Australia, 3175
Northern Hospital Recruiting
Epping, Victoria, Australia, 3076
Contact: Angaj Ghosh   
Contact: John Green   
Principal Investigator: Angaj Ghosh         
Sub-Investigator: John Green         
St Vincent's Hospital (Melbourne) Recruiting
Fitzroy, Victoria, Australia, 3065
Contact: Antony Tobin   
Contact: John Santamaria   
Principal Investigator: Antony Tobin         
Sub-Investigator: John Santamaria         
Western Hospital Recruiting
Footscray, Victoria, Australia, 3011
Contact: Craig French   
Contact: Forbes McGain   
Principal Investigator: Craig French         
Sub-Investigator: Forbes McGain         
Geelong Hospital (Barwon Health) Recruiting
Geelong, Victoria, Australia, 3220
Contact: Martina Chonghaile   
Contact: Neil Orford   
Sub-Investigator: Martina Chonghaile         
Principal Investigator: Neil Orford         
Austin Hospital Recruiting
Heidelburg, Victoria, Australia, 3084
Contact: Rinaldo Bellomo   
Contact: Daryl Jones   
Principal Investigator: Rinaldo Bellomo         
Sub-Investigator: Daryl Jones         
Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Contact: Rohit D'Costa   
Contact: Shyama Sriram   
Principal Investigator: Rohit D'Costa         
Sub-Investigator: Shyama Sriram         
Sunshine Hospital Recruiting
St Albans, Victoria, Australia, 3021
Contact: Craig French   
Principal Investigator: Craig Fench         
Sub-Investigator: Forbes McGain         
Australia, Western Australia
Fiona Stanley (Fremantle) Hospital Completed
Fremantle, Western Australia, Australia, 6959
Fiona Stanley Hospital Recruiting
Murdoch, Western Australia, Australia, 6150
Contact: Adrian Regli   
Principal Investigator: Adrian Regli         
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Contact: Chris Allen   
Contact: Edward Litton   
Sub-Investigator: Edward Litton         
Principal Investigator: Chris Allen         
St John of God Hospital-Murdoch Recruiting
Perth, Western Australia, Australia, 6150
Contact: Adrian Regli    0420790102      
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Anders Perner   
Principal Investigator: Anders Perner         
Sub-Investigator: Rasmus Muller         
Cork University Hospital Withdrawn
Cork, Ireland
New Zealand
North Shore Hospital Recruiting
North Shore City, Auckland, New Zealand, 0622
Contact: Janet Liang   
Principal Investigator: Janet Liang         
Waikato Hospital Active, not recruiting
Hamilton, NZ, New Zealand, 3240
Auckland City Hospital (CVICU) Recruiting
Auckland, New Zealand, 1142
Contact: Shay McGuinness   
Principal Investigator: Shay McGuinness         
Auckland City Hospital (DCCM) Recruiting
Auckland, New Zealand, 1142
Contact: Colin Macarthur   
Principal Investigator: Colin Macarthur         
Middlemore Hospital Recruiting
Auckland, New Zealand, 1640
Contact: Alex Kazemi   
Contact: Tony Williams   
Principal Investigator: Alex Kazemi         
Sub-Investigator: Tony Williams         
Christchurch Hospital Recruiting
Christchurch, New Zealand, 8011
Contact: Seton Henderson   
Contact: David Knight   
Principal Investigator: Seton Henderson         
Sub-Investigator: David Knight         
Tauranga Hospital Recruiting
Tauranga, New Zealand, 3110
Contact: Troy Browne   
Principal Investigator: Troy Browne         
Wellington Hospital Recruiting
Wellington, New Zealand, 6011
Contact: Paul Young   
Contact: Richard Dinsdale   
Principal Investigator: Paul Young         
Sub-Investigator: Richard Dinsdale         
Saudi Arabia
King Abdul Aziz Medical City Recruiting
Riyadh, Saudi Arabia, 11426
Contact: Yaseen Arabi   
Principal Investigator: Yaseen Arabi         
Sub-Investigator: Samir Hadad         
King Khalid University Hospital Recruiting
Riyadh, Saudi Arabia, 11472
Contact: Ahmed Abdulmomen       aturk@KSU.EDU.SA   
Contact: Mariam Al-Ansari   
Principal Investigator: Ahmed Abdulmomen         
Sub-Investigator: Mariam Al-Ansari         
King Fahad Medical City Recruiting
Riyadh, Saudi Arabia, 11525
Contact: Hani Lababidi   
Contact: Mohammad Al Tannir         
Principal Investigator: Hani Lababidi         
Sub-Investigator: Mohammad Al Tannir         
United Kingdom
Queen Elizabeth Hospital Birmingham Recruiting
Edgbaston, Birmingham, United Kingdom, B15 2TH
Contact: Tony Whitehouse   
Principal Investigator: Tony Whitehouse         
Sub-Investigator: Catherine Snelson         
Queen Alexandra Hospital (Portsmouth) Recruiting
Cosham, Portsmouth, United Kingdom, PO63LY
Contact: David Pogson   
Principal Investigator: David Pogson         
Ashford & St.Peter's NHS Foundation Trust Recruiting
Chertsey, Surrey, United Kingdom, KT16 0PZ
Contact: Ian White       Ian White <>   
Principal Investigator: Ian White         
Royal Surrey County Hospital Recruiting
Guildford, Surrey, United Kingdom, GU2 7XX
Contact: Lui Forni,   
Principal Investigator: Lui Forni         
Sub-Investigator: Ben Creagh-Brown         
Sub-Investigator: Justin Kirk-Bayley         
Freeman Hospital Recruiting
Newcaslte Upon Tyne, Tyne & Wear, United Kingdom, NE7 7DN
Contact: Stephen Wright   
Principal Investigator: Stephen Wright         
Royal Victoria Infirmary Withdrawn
Newcastle Upon Tyne, Tyne & Wear, United Kingdom, NE1 4LP
University Hospital of Wales Withdrawn
Cardiff, Wales, United Kingdom, CF14 4XW
Royal Gwent Hospital Recruiting
Newport, Wales, United Kingdom, NP20 2UB
Contact: Nicholas Mason   
Principal Investigator: Nicholas Mason         
Sub-Investigator: Jack Parry-Jones         
Bristol Royal Infirmary Recruiting
Bristol, United Kingdom, BS2 8HW
Contact: Jeremy Bewley   
Principal Investigator: Jeremy Bewley         
Sub-Investigator: Sanjoy Shah         
Lewisham Healthcare NHS Trust Recruiting
London, United Kingdom, SE 13 6LH
Contact: Oliver Rose   
Principal Investigator: Oliver Rose         
Sub-Investigator: Marthinus Mostert         
Sub-Investigator: Ashraf Molokhia         
Guy's and St Thomas' HNS Foundation Trust Recruiting
London, United Kingdom, SE1 9RT
Contact: Marlies Ostermann   
Principal Investigator: Marlies Ostermann         
Sub-Investigator: Richard Beale         
King's College Hospital NHS Foundation Trust Recruiting
London, United Kingdom, SE5 9RS
Contact: Phillip Hopkins   
Principal Investigator: Phillip Hopkins         
Sub-Investigator: Julia Wendon         
St Georges Healthcare NHS Trust Recruiting
London, United Kingdom, SW17 0QH
Contact: Andrew Rhodes   
Principal Investigator: Andrew Rhodes         
Sub-Investigator: Aya Hollmann         
University Hospital Southampton Recruiting
Southampton, United Kingdom, S016 6YD
Contact: Max Jonas   
Principal Investigator: Max Jonas         
Sub-Investigator: Rebecca Cusack         
Sponsors and Collaborators
The George Institute
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Study Chair: Balasubramanian Venkatesh The George Institute
  More Information

Responsible Party: The George Institute Identifier: NCT01448109     History of Changes
Other Study ID Numbers: GI-CCT372273
Study First Received: October 5, 2011
Last Updated: October 17, 2016

Keywords provided by The George Institute:

Additional relevant MeSH terms:
Shock, Septic
Critical Illness
Pathologic Processes
Systemic Inflammatory Response Syndrome
Disease Attributes
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Anti-Inflammatory Agents processed this record on March 27, 2017