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

This study is ongoing, but not recruiting participants.
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: May 2, 2017
Last verified: May 2017
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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. ]

Enrollment: 3800
Actual Study Start Date: June 13, 2012
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: July 22, 2017 (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   (Adult, Senior)
Sexes Eligible for Study:   All
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
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 ClinicalTrials.gov identifier: NCT01448109

  Hide Study Locations
Locations
Australia, New South Wales
Blacktown Hospital
Blacktown, New South Wales, Australia, 2148
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
St Vincent's Hospital
Darlinghurst, New South Wales, Australia, 2010
Gosford Hospital
Gosford, New South Wales, Australia, 2250
St George Hospital
Kogarah, New South Wales, Australia, 2217
Liverpool Hospital
Liverpool, New South Wales, Australia, 1871
John Hunter Hospital
Newcastle, New South Wales, Australia, 2305
Nepean Hospital
Penrith, New South Wales, Australia, 2747
Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Royal North Shore Hospital
St Leonards, New South Wales, Australia, 2065
The George Institute for Global Health
Sydney, New South Wales, Australia, 2000
Tamworth Rural Referral Hospital
Tamworth, New South Wales, Australia, 2340
Tweed Heads District Hospital
Tweed Heads, New South Wales, Australia, 2485
Calvary Mater Hospital (Newcastle)
Waratah, New South Wales, Australia, 2298
Wollongong Hospital
Wollongong, New South Wales, Australia, 2521
Australia, Northern Territory
Royal Darwin Hospital
Darwin, Northern Territory, Australia, 0810
Australia, Queensland
Wesley Hospital
Auchenflower, Queensland, Australia, 4066
Prince Charles Hospital
Brisbane, Queensland, Australia, 4032
Mater Health Services
Brisbane, Queensland, Australia, 4101
Gold Coast University Hospital
Gold Coast, Queensland, Australia, 4215
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4029
Ipswich Hospital
Ipswich, Queensland, Australia, 4307
Logan Hospital
Logan, Queensland, Australia, 4131
Mackay Base Hospital
Mackay, Queensland, Australia, 4740
Nambour Hospital
Nambour, Queensland, Australia, 4560
Redcliffe Hospital
Redcliffe, Queensland, Australia, 4020
Toowoomba Hospital
Toowoomba, Queensland, Australia, 4350
Townsville Hospital
Townsville, Queensland, Australia, 4814
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Lyell McEwin Hospital
Elizabeth Vale, South Australia, Australia, 5112
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia, 5011
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Bendigo Hospital
Bendigo, Victoria, Australia, 3550
Monash Medical Centre
Clayton, Victoria, Australia, 3168
Northern Hospital
Epping, Victoria, Australia, 3076
St Vincent's Hospital (Melbourne)
Fitzroy, Victoria, Australia, 3065
Footscray Hospital
Footscray, Victoria, Australia, 3011
Geelong Hospital (Barwon Health)
Geelong, Victoria, Australia, 3220
Austin Hospital
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Sunshine Hospital
St Albans, Victoria, Australia, 3021
Australia, Western Australia
Fremantle Hospital
Fremantle, Western Australia, Australia, 6959
Fiona Stanley Hospital
Murdoch, Western Australia, Australia, 6150
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
St John of God Hospital-Murdoch
Perth, Western Australia, Australia, 6150
Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
New Zealand
North Shore Hospital
North Shore, Auckland, New Zealand, 0622
Waikato Hospital
Hamilton, NZ, New Zealand, 3240
Auckland City Hospital (CVICU)
Auckland, New Zealand, 1142
Auckland City Hospital (DCCM)
Auckland, New Zealand, 1142
Middlemore Hospital
Auckland, New Zealand, 1640
Christchurch Hospital
Christchurch, New Zealand, 8011
Tauranga Hospital
Tauranga, New Zealand, 3110
Wellington Hospital
Wellington, New Zealand, 6011
Saudi Arabia
King Abdul Aziz Medical City
Riyadh, Saudi Arabia, 11426
King Khalid University Hospital
Riyadh, Saudi Arabia, 11472
King Fahad Medical City
Riyadh, Saudi Arabia, 11525
United Kingdom
Queen Elizabeth Hospital Birmingham
Edgbaston, Birmingham, United Kingdom, B15 2TH
Queen Alexandra Hospital (Portsmouth)
Cosham, Portsmouth, United Kingdom, PO63LY
Ashford & St.Peter's NHS Foundation Trust
Chertsey, Surrey, United Kingdom, KT16 0PZ
Royal Surrey County Hospital
Guildford, Surrey, United Kingdom, GU2 7XX
Freeman Hospital
Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE7 7DN
Royal Gwent Hospital
Newport, Wales, United Kingdom, NP20 2UB
Bristol Royal Infirmary
Bristol, United Kingdom, BS2 8HW
Lewisham Healthcare NHS Trust
London, United Kingdom, SE 13 6LH
Guy's and St Thomas' HNS Foundation Trust
London, United Kingdom, SE1 9RT
King's College Hospital NHS Foundation Trust
London, United Kingdom, SE5 9RS
St Georges Healthcare NHS Trust
London, United Kingdom, SW17 0QH
University Hospital Southampton
Southampton, United Kingdom, S016 6YD
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

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: May 2, 2017

Keywords provided by The George Institute:
Sepsis
Corticosteroid

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

ClinicalTrials.gov processed this record on August 21, 2017