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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01448109




Registration number
NCT01448109
Ethics application status
Date submitted
5/10/2011
Date registered
7/10/2011
Date last updated
12/12/2017

Titles & IDs
Public title
ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock
Scientific title
A Randomised Blinded Placebo Controlled Trial of Hydrocortisone in Critically Ill Patients With Septic Shock
Secondary ID [1] 0 0
GI-CCT372273
Universal Trial Number (UTN)
Trial acronym
ADRENAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Septic Shock 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Hydrocortisone
Treatment: Drugs - Sterile air filled vial

Active Comparator: Hydrocortisone -

Placebo Comparator: Sterile air filled vial -


Treatment: Drugs: 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.

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All cause mortality at 90 days after randomisation
Timepoint [1] 0 0
90 days after randomisation
Secondary outcome [1] 0 0
All-cause mortality at 28 days and 6 months after randomisation
Timepoint [1] 0 0
28 days and 6 months after randomisation
Secondary outcome [2] 0 0
Time to resolution of shock
Timepoint [2] 0 0
MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation.
Secondary outcome [3] 0 0
Recurrence of shock
Timepoint [3] 0 0
Up to90 days after randomisation
Secondary outcome [4] 0 0
Duration of ICU stay
Timepoint [4] 0 0
Up to 90 days after randomisation
Secondary outcome [5] 0 0
Duration of hospital stay
Timepoint [5] 0 0
Up to 90 days after randomisation
Secondary outcome [6] 0 0
Frequency and duration of mechanical ventilation
Timepoint [6] 0 0
Up to 90 days after randomisation
Secondary outcome [7] 0 0
Duration of renal replacement therapy
Timepoint [7] 0 0
Up to 90 days after randomisation
Secondary outcome [8] 0 0
Development of bacteraemia
Timepoint [8] 0 0
2 and 14 days post randomisation
Secondary outcome [9] 0 0
Bleeding requiring blood transfusions received in the ICU
Timepoint [9] 0 0
Up to 90 days after randomisation
Secondary outcome [10] 0 0
Quality of Life assessment at 6 months.
Timepoint [10] 0 0
6 months.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/11/2017
Sample size
Target
Accrual to date
Final
3800
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [4] 0 0
Gosford Hospital - Gosford
Recruitment hospital [5] 0 0
St George Hospital - Kogarah
Recruitment hospital [6] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [8] 0 0
Nepean Hospital - Penrith
Recruitment hospital [9] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [10] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 0 0
The George Institute for Global Health - Sydney
Recruitment hospital [12] 0 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [13] 0 0
Tweed Heads District Hospital - Tweed Heads
Recruitment hospital [14] 0 0
Calvary Mater Hospital (Newcastle) - Waratah
Recruitment hospital [15] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [16] 0 0
Royal Darwin Hospital - Darwin
Recruitment hospital [17] 0 0
Wesley Hospital - Auchenflower
Recruitment hospital [18] 0 0
Prince Charles Hospital - Brisbane
Recruitment hospital [19] 0 0
Mater Health Services - Brisbane
Recruitment hospital [20] 0 0
Gold Coast University Hospital - Gold Coast
Recruitment hospital [21] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [22] 0 0
Ipswich Hospital - Ipswich
Recruitment hospital [23] 0 0
Logan Hospital - Logan
Recruitment hospital [24] 0 0
Mackay Base Hospital - Mackay
Recruitment hospital [25] 0 0
Nambour Hospital - Nambour
Recruitment hospital [26] 0 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [27] 0 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [28] 0 0
Townsville Hospital - Townsville
Recruitment hospital [29] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [30] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [31] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [32] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [33] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [34] 0 0
Bendigo Hospital - Bendigo
Recruitment hospital [35] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [36] 0 0
Northern Hospital - Epping
Recruitment hospital [37] 0 0
St Vincent's Hospital (Melbourne) - Fitzroy
Recruitment hospital [38] 0 0
Footscray Hospital - Footscray
Recruitment hospital [39] 0 0
Geelong Hospital (Barwon Health) - Geelong
Recruitment hospital [40] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [41] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [42] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [43] 0 0
Fremantle Hospital - Fremantle
Recruitment hospital [44] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [45] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [46] 0 0
St John of God Hospital-Murdoch - Perth
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2250 - Gosford
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
1871 - Liverpool
Recruitment postcode(s) [7] 0 0
2305 - Newcastle
Recruitment postcode(s) [8] 0 0
2747 - Penrith
Recruitment postcode(s) [9] 0 0
2031 - Randwick
Recruitment postcode(s) [10] 0 0
2065 - St Leonards
Recruitment postcode(s) [11] 0 0
2000 - Sydney
Recruitment postcode(s) [12] 0 0
2340 - Tamworth
Recruitment postcode(s) [13] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [14] 0 0
2298 - Waratah
Recruitment postcode(s) [15] 0 0
2521 - Wollongong
Recruitment postcode(s) [16] 0 0
0810 - Darwin
Recruitment postcode(s) [17] 0 0
4066 - Auchenflower
Recruitment postcode(s) [18] 0 0
4032 - Brisbane
Recruitment postcode(s) [19] 0 0
4101 - Brisbane
Recruitment postcode(s) [20] 0 0
4215 - Gold Coast
Recruitment postcode(s) [21] 0 0
4029 - Herston
Recruitment postcode(s) [22] 0 0
4307 - Ipswich
Recruitment postcode(s) [23] 0 0
4131 - Logan
Recruitment postcode(s) [24] 0 0
4740 - Mackay
Recruitment postcode(s) [25] 0 0
4560 - Nambour
Recruitment postcode(s) [26] 0 0
4020 - Redcliffe
Recruitment postcode(s) [27] 0 0
4350 - Toowoomba
Recruitment postcode(s) [28] 0 0
4814 - Townsville
Recruitment postcode(s) [29] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [30] 0 0
5000 - Adelaide
Recruitment postcode(s) [31] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [32] 0 0
5011 - Woodville South
Recruitment postcode(s) [33] 0 0
7000 - Hobart
Recruitment postcode(s) [34] 0 0
3550 - Bendigo
Recruitment postcode(s) [35] 0 0
3168 - Clayton
Recruitment postcode(s) [36] 0 0
3076 - Epping
Recruitment postcode(s) [37] 0 0
3065 - Fitzroy
Recruitment postcode(s) [38] 0 0
3011 - Footscray
Recruitment postcode(s) [39] 0 0
3220 - Geelong
Recruitment postcode(s) [40] 0 0
3084 - Heidelberg
Recruitment postcode(s) [41] 0 0
3050 - Parkville
Recruitment postcode(s) [42] 0 0
3021 - St Albans
Recruitment postcode(s) [43] 0 0
6959 - Fremantle
Recruitment postcode(s) [44] 0 0
6150 - Murdoch
Recruitment postcode(s) [45] 0 0
6000 - Perth
Recruitment postcode(s) [46] 0 0
6150 - Perth
Recruitment outside Australia
Country [1] 0 0
Denmark
State/province [1] 0 0
Copenhagen
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland
Country [3] 0 0
New Zealand
State/province [3] 0 0
NZ
Country [4] 0 0
New Zealand
State/province [4] 0 0
Christchurch
Country [5] 0 0
New Zealand
State/province [5] 0 0
Tauranga
Country [6] 0 0
New Zealand
State/province [6] 0 0
Wellington
Country [7] 0 0
Saudi Arabia
State/province [7] 0 0
Riyadh
Country [8] 0 0
United Kingdom
State/province [8] 0 0
England
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Wales

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australian and New Zealand Intensive Care Society Clinical Trials Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01448109
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Balasubramanian Venkatesh
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01448109