ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock
- Conditions
- Septic Shock
- Interventions
- Drug: Sterile air filled vial
- Registration Number
- NCT01448109
- Lead Sponsor
- The George Institute
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3800
-
Aged 18 years or older
-
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.
-
Being treated with mechanical ventilation at the time of randomisation
-
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
-
Administration of vasopressors or inotropes for = 4 hours and present at time of randomisation.
- Met all inclusion criteria more than 24 hours ago
- Clinician expects to prescribe systemic corticosteroids for an indication other than septic shock (not including nebulised or inhaled corticosteroid)
- Patients treated with etomidate
- Patients receiving treatment with Amphotericin B for systemic fungal infections at time of randomisation
- Patients with documented cerebral malaria at the time of randomisation
- Patients with documented strongyloides infection at the time of randomisation
- 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
- Death from underlying disease is likely within 90 days
- Patient has been previously enrolled in the ADRENAL study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sterile air filled vial Sterile air filled vial - Hydrocortisone Hydrocortisone -
- Primary Outcome Measures
Name Time Method All cause mortality at 90 days after randomisation 90 days after randomisation
- Secondary Outcome Measures
Name Time Method Development of bacteraemia 2 and 14 days post randomisation Duration of hospital stay Up to 90 days after randomisation Duration of ICU stay Up to 90 days after randomisation Bleeding requiring blood transfusions received in the ICU Up to 90 days after randomisation All-cause mortality at 28 days and 6 months after randomisation 28 days and 6 months after randomisation Recurrence of shock Up to90 days after randomisation Recurrence of shock - defined as a new episode of shock after reversal of the initial episode.
Frequency and duration of mechanical ventilation Up to 90 days after randomisation Quality of Life assessment at 6 months. 6 months. Time to resolution of shock 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.
Duration of renal replacement therapy Up to 90 days after randomisation
Trial Locations
- Locations (70)
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
The George Institute for Global Health
🇦🇺Sydney, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
St Vincent's Hospital (Melbourne)
🇦🇺Fitzroy, Victoria, Australia
Lewisham Healthcare NHS Trust
🇬🇧London, England, United Kingdom
Guy's and St Thomas' HNS Foundation Trust
🇬🇧London, England, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, England, United Kingdom
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Nepean Hospital
🇦🇺Penrith, New South Wales, Australia
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
St Vincent's Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
John Hunter Hospital
🇦🇺Newcastle, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Tamworth Rural Referral Hospital
🇦🇺Tamworth, New South Wales, Australia
Wollongong Hospital
🇦🇺Wollongong, New South Wales, Australia
Tweed Heads District Hospital
🇦🇺Tweed Heads, New South Wales, Australia
Calvary Mater Hospital (Newcastle)
🇦🇺Waratah, New South Wales, Australia
Mater Health Services
🇦🇺Brisbane, Queensland, Australia
Wesley Hospital
🇦🇺Auchenflower, Queensland, Australia
Ipswich Hospital
🇦🇺Ipswich, Queensland, Australia
Gold Coast University Hospital
🇦🇺Gold Coast, Queensland, Australia
Prince Charles Hospital
🇦🇺Brisbane, Queensland, Australia
Mackay Base Hospital
🇦🇺Mackay, Queensland, Australia
Redcliffe Hospital
🇦🇺Redcliffe, Queensland, Australia
Logan Hospital
🇦🇺Logan, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Nambour Hospital
🇦🇺Nambour, Queensland, Australia
Townsville Hospital
🇦🇺Townsville, Queensland, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
North Shore Hospital
🇳🇿North Shore, Auckland, New Zealand
Waikato Hospital
🇳🇿Hamilton, NZ, New Zealand
Auckland City Hospital (DCCM)
🇳🇿Auckland, New Zealand
Auckland City Hospital (CVICU)
🇳🇿Auckland, New Zealand
Middlemore Hospital
🇳🇿Auckland, New Zealand
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Wellington Hospital
🇳🇿Wellington, New Zealand
King Khalid University Hospital, King Saud University
🇸🇦Riyadh, Saudi Arabia
Queen Elizabeth Hospital Birmingham
🇬🇧Edgbaston, England, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, England, United Kingdom
University Hospital Southampton
🇬🇧Southampton, England, United Kingdom
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Fremantle Hospital
🇦🇺Fremantle, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Rigshospitalet
🇩🇰Copenhagen, Denmark
St Georges Healthcare NHS Trust
🇬🇧London, England, United Kingdom
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Northern Hospital
🇦🇺Epping, Victoria, Australia
Toowoomba Hospital
🇦🇺Toowoomba, Queensland, Australia
Footscray Hospital
🇦🇺Footscray, Victoria, Australia
Royal Gwent Hospital
🇬🇧Newport, Wales, United Kingdom
King Abdulaziz Medical City
🇸🇦Riyadh, Saudi Arabia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Ashford & St.Peter's NHS Foundation Trust
🇬🇧Chertsey, England, United Kingdom
Queen Alexandra Hospital (Portsmouth)
🇬🇧Cosham, England, United Kingdom
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
King Fahad Medical City
🇸🇦Riyadh, Saudi Arabia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Freeman Hospital
🇬🇧Newcastle upon Tyne, England, United Kingdom
Geelong Hospital (Barwon Health)
🇦🇺Geelong, Victoria, Australia
Bristol Royal Infirmary
🇬🇧Bristol, England, United Kingdom
St John of God Hospital-Murdoch
🇦🇺Perth, Western Australia, Australia
Royal Darwin Hospital
🇦🇺Darwin, Northern Territory, Australia