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Trial registered on ANZCTR
Registration number
ACTRN12611001042932
Ethics application status
Approved
Date submitted
28/09/2011
Date registered
5/10/2011
Date last updated
27/06/2019
Date data sharing statement initially provided
27/06/2019
Date results information initially provided
27/06/2019
Type of registration
Prospectively registered
Titles & IDs
Public title
A randomised blinded placebo controlled trial of hydrocortisone in critically ill patients with septic shock.
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Scientific title
A multi-centre, blinded, randomised, placebo controlled trial to determine whether hydrocortisone therapy reduces 90-day mortality in patients admitted to intensive Care with septic shock.
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Secondary ID [1]
263097
0
Nil
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Universal Trial Number (UTN)
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Trial acronym
ADRENAL
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Septic shock
270850
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Condition category
Condition code
Infection
271027
271027
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0
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Studies of infection and infectious agents
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Hydrocortisone 200mg per day given intravenously as a continuous infusion for 7 days
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Intervention code [1]
269444
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Treatment: Drugs
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Comparator / control treatment
"Sterile air filled vial" that contained 0.2ml of water for injection for sterilisation purposes. It will be reconstituted with water for injection, diluted and given as a continuous infusion (2 per day) for 7 days.
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Control group
Placebo
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Outcomes
Primary outcome [1]
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All cause mortality at 90 days after randomisation
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Assessment method [1]
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Timepoint [1]
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90 days after randomisation
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Secondary outcome [1]
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All-cause mortality at 28 days and 6 months after randomisation
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Assessment method [1]
294203
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Timepoint [1]
294203
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28 days and 6 months after randomisation
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Secondary outcome [2]
294204
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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.
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Assessment method [2]
294204
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Timepoint [2]
294204
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MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation.
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Secondary outcome [3]
294205
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Recurrence of shock - defined as a new episode of shock after reversal of the initial episode.
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Assessment method [3]
294205
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Timepoint [3]
294205
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Up to90 days after randomisation
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Secondary outcome [4]
294206
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Duration of ICU stay
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Assessment method [4]
294206
0
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Timepoint [4]
294206
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Up to 90 days after randomisation
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Secondary outcome [5]
294207
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Duration of hospital stay
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Assessment method [5]
294207
0
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Timepoint [5]
294207
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Up to 90 days after randomisation
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Secondary outcome [6]
294208
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Frequency and duration of mechanical ventilation
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Assessment method [6]
294208
0
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Timepoint [6]
294208
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Up to 90 days after randomisation
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Secondary outcome [7]
294209
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Duration of renal replacement therapy
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Assessment method [7]
294209
0
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Timepoint [7]
294209
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Up to 90 days after randomisation
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Secondary outcome [8]
294210
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Development of bacteraemia between 2 and 14 days post randomisation
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Assessment method [8]
294210
0
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Timepoint [8]
294210
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2 and 14 days post randomisation
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Secondary outcome [9]
294211
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Bleeding requiring blood transfusions received in the ICU
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Assessment method [9]
294211
0
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Timepoint [9]
294211
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Up to 90 days after randomisation
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Secondary outcome [10]
294212
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Quality of Life - EQ5D assessment at 6 months.
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Assessment method [10]
294212
0
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Timepoint [10]
294212
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6 months.
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Eligibility
Key inclusion criteria
1. Aged 18 years or older 2. Documented site of infection, or strong suspicion of infection 3. 2 of the 4 clinical signs of inflammation: i. Core temperature > 38 degrees C or < 35 degrees C ii. Heart rate > 90 beats per minute iii. White cell count > 12 x 109/L or < 4 x 109/L or > 10% immature neutrophils iv. Respiratory rate > 20 breaths per minute, or PaCO2 < 32 mmHg, or mechanical ventilation. 4. Being treated with mechanical ventilation at the time of randomisation 5. 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 6. Administration of vasopressors or inotropes for greater than or equal to 4 hours and present at time of randomisation.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be achieved using a minimisation algorithm via a password-protected encrypted web based interface. Randomisation will be stratified according to participating site and operative or non-operative admission to the ICU. Following successful randomisation, each patient will be assigned a unique ‘patient study number’ and a unique ‘study treatment number’. The unique study treatment number is matched to blinded study treatment with sufficient study drug to last the 7 day course of treatment.
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be achieved using a minimisation algorithm.
Stratification will occur at centre level and by operative and non operative.
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Masking / blinding
Blinded (masking used)
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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
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
Efficacy
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Date of first participant enrolment
Anticipated
1/06/2012
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Actual
13/06/2012
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Date of last participant enrolment
Anticipated
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Actual
21/04/2017
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Date of last data collection
Anticipated
21/11/2017
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Actual
21/11/2018
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Sample size
Target
3800
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Accrual to date
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Final
3800
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Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,TAS,WA,VIC
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Recruitment hospital [1]
5134
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Blacktown Hospital - Blacktown
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Recruitment hospital [2]
5135
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Calvary Mater Newcastle - Waratah
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Recruitment hospital [3]
5136
0
John Hunter Hospital Royal Newcastle Centre - New Lambton
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Recruitment hospital [4]
5137
0
Liverpool Hospital - Liverpool
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Recruitment hospital [5]
5138
0
Nepean Hospital - Kingswood
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Recruitment hospital [6]
5139
0
Prince of Wales Hospital - Randwick
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Recruitment hospital [7]
5140
0
Royal North Shore Hospital - St Leonards
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Recruitment hospital [8]
5141
0
Royal Prince Alfred Hospital - Camperdown
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Recruitment hospital [9]
5142
0
St George Hospital - Kogarah
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Recruitment hospital [10]
5143
0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
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Recruitment hospital [11]
5144
0
Tamworth Rural Referral Hospital - Tamworth
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Recruitment hospital [12]
5145
0
The Tweed Hospital - Tweed Heads
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Recruitment hospital [13]
5146
0
Wollongong Hospital - Wollongong
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Recruitment hospital [14]
5147
0
Gold Coast Hospital - Southport
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Recruitment hospital [15]
5148
0
Ipswich Hospital - Ipswich
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Recruitment hospital [16]
5149
0
Logan Hospital - Meadowbrook
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Recruitment hospital [17]
5150
0
Mater Private Hospital - South Brisbane
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Recruitment hospital [18]
5151
0
Mackay Base Hospital - Mackay
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Recruitment hospital [19]
5152
0
Nambour General Hospital - Nambour
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Recruitment hospital [20]
5153
0
Princess Alexandra Hospital - Woolloongabba
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Recruitment hospital [21]
5154
0
Redcliffe Hospital - Redcliffe
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Recruitment hospital [22]
5155
0
Royal Brisbane & Womens Hospital - Herston
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Recruitment hospital [23]
5157
0
Toowoomba Hospital - Toowoomba
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Recruitment hospital [24]
5158
0
The Townsville Hospital - Douglas
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Recruitment hospital [25]
5159
0
The Wesley Hospital - Auchenflower
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Recruitment hospital [26]
5160
0
Royal Darwin Hospital - Tiwi
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Recruitment hospital [27]
5161
0
Lyell McEwin Hospital - Elizabeth Vale
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Recruitment hospital [28]
5162
0
The Royal Adelaide Hospital - Adelaide
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Recruitment hospital [29]
5163
0
The Queen Elizabeth Hospital - Woodville
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Recruitment hospital [30]
5164
0
Royal Hobart Hospital - Hobart
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Recruitment hospital [31]
5165
0
Austin Health - Austin Hospital - Heidelberg
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Recruitment hospital [32]
5166
0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
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Recruitment hospital [33]
5167
0
Barwon Health - Geelong Hospital campus - Geelong
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Recruitment hospital [34]
5168
0
Monash Medical Centre - Clayton campus - Clayton
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Recruitment hospital [35]
5169
0
The Northern Hospital - Epping
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Recruitment hospital [36]
5170
0
Royal Melbourne Hospital - City campus - Parkville
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Recruitment hospital [37]
5171
0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
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Recruitment hospital [38]
5172
0
Western Hospital - Footscray
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Recruitment hospital [39]
5173
0
Fremantle Hospital and Health Service - Fremantle
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Recruitment hospital [40]
5174
0
Royal Perth Hospital - Perth
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Recruitment hospital [41]
5175
0
Gold Coast Hospital - Southport
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Recruitment hospital [42]
5177
0
The Prince Charles Hospital - Chermside
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Recruitment hospital [43]
5178
0
Fiona Stanley Hospital - Murdoch
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Recruitment hospital [44]
7937
0
Gosford Hospital - Gosford
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Recruitment hospital [45]
7938
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St John of God Hospital, Murdoch - Murdoch
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Recruitment postcode(s) [1]
12598
0
2148 - Blacktown
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Recruitment postcode(s) [2]
12599
0
2298 - Waratah
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Recruitment postcode(s) [3]
12600
0
2305 - New Lambton
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Recruitment postcode(s) [4]
12601
0
1871 - Liverpool
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Recruitment postcode(s) [5]
12602
0
2747 - Kingswood
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Recruitment postcode(s) [6]
12603
0
2031 - Randwick
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Recruitment postcode(s) [7]
12604
0
2065 - St Leonards
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Recruitment postcode(s) [8]
12605
0
2050 - Camperdown
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Recruitment postcode(s) [9]
12606
0
2217 - Kogarah
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Recruitment postcode(s) [10]
12607
0
2010 - Darlinghurst
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Recruitment postcode(s) [11]
12608
0
2340 - Tamworth
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Recruitment postcode(s) [12]
12609
0
2485 - Tweed Heads
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Recruitment postcode(s) [13]
12610
0
2521 - South Coast Mc
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Recruitment postcode(s) [14]
12611
0
4215 - Southport
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Recruitment postcode(s) [15]
12612
0
4305 - Ipswich
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Recruitment postcode(s) [16]
12613
0
4131 - Meadowbrook
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Recruitment postcode(s) [17]
12614
0
4101 - South Brisbane
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Recruitment postcode(s) [18]
12615
0
4740 - Mackay
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Recruitment postcode(s) [19]
12616
0
4560 - Nambour
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Recruitment postcode(s) [20]
12617
0
4102 - Woolloongabba
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Recruitment postcode(s) [21]
12618
0
4020 - Redcliffe
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Recruitment postcode(s) [22]
12619
0
4006 - Herston
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Recruitment postcode(s) [23]
12621
0
4350 - Toowoomba
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Recruitment postcode(s) [24]
12622
0
4814 - Douglas
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Recruitment postcode(s) [25]
12623
0
4066 - Auchenflower
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Recruitment postcode(s) [26]
12624
0
0810 - Tiwi
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Recruitment postcode(s) [27]
12625
0
5112 - Elizabeth Vale
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Recruitment postcode(s) [28]
12626
0
5000 - Adelaide
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Recruitment postcode(s) [29]
12627
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5011 - Woodville South
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Recruitment postcode(s) [30]
12628
0
7000 - Hobart
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Recruitment postcode(s) [31]
12629
0
3084 - Heidelberg
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Recruitment postcode(s) [32]
12630
0
3550 - Bendigo
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Recruitment postcode(s) [33]
12631
0
3220 - Geelong
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Recruitment postcode(s) [34]
12632
0
3168 - Clayton
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Recruitment postcode(s) [35]
12633
0
3076 - Epping
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Recruitment postcode(s) [36]
12634
0
3050 - Royal Melbourne Hospital
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Recruitment postcode(s) [37]
12635
0
3065 - Fitzroy
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Recruitment postcode(s) [38]
12636
0
3011 - Footscray
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Recruitment postcode(s) [39]
12637
0
6959 - Fremantle
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Recruitment postcode(s) [40]
12638
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6000 - Perth
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Recruitment postcode(s) [41]
15905
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2250 - Gosford
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Recruitment postcode(s) [42]
15906
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6150 - Murdoch
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Recruitment outside Australia
Country [1]
3858
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Denmark
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State/province [1]
3858
0
Copenhagen
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Country [2]
3861
0
United Kingdom
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State/province [2]
3861
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England
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Country [3]
3862
0
Saudi Arabia
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State/province [3]
3862
0
Riyadh
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Country [4]
8875
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New Zealand
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State/province [4]
8875
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North and South Island
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Funding & Sponsors
Funding source category [1]
269921
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Government body
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Name [1]
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Australian National Health and Medical Research Council (NHMRC)
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Address [1]
269921
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Level 1, 16 Marcus Clarke Street, Canberra ACT 2601
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Country [1]
269921
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Australia
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Funding source category [2]
285599
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Government body
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Name [2]
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Health Research Council of New Zealand
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Address [2]
285599
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Level 3, 110 Stanley Street,
Auckland, PO Box 5541,
Wellesley Street,
Auckland 1010, New Zealand
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Country [2]
285599
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New Zealand
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Primary sponsor type
Other Collaborative groups
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Name
The George Institute for Global Health
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Address
Level 3, 50 Bridge Street, Sydney, NSW, 2000, Australia
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Country
Australia
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Secondary sponsor category [1]
268938
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None
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Name [1]
268938
0
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Address [1]
268938
0
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Country [1]
268938
0
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Other collaborator category [1]
252268
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Other Collaborative groups
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Name [1]
252268
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Australian and New Zealand Intensive Care Society Clinical Trials Group
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Address [1]
252268
0
10 Levers Terrace
Carlton South
VIC 3053
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Country [1]
252268
0
Australia
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
271906
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Sydney South West Area Health Service Human Research Ethics Review Committee (RPAH Zone)
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Ethics committee address [1]
271906
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Research Development Office
Royal Prince Alfred Hospital
Missenden Road,
CAMPERDOWN NSW 2050
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Ethics committee country [1]
271906
0
Australia
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Date submitted for ethics approval [1]
271906
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Approval date [1]
271906
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04/07/2011
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Ethics approval number [1]
271906
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EC00113
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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.
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Trial website
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Trial related presentations / publications
Publication: Venkatesh B, Myburgh J, Finfer S, Webb S, Cohen J, Bellomo R, McArthur C, Joyce C, Rajbhandari D, Glass P, Harward M and the ANZICS CTG Investigators. The ADRENAL protocol paper. Crit Care Resus 2013;15:83-88.
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Public notes
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Contacts
Principal investigator
Name
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Prof Balasubramanian Venkatesh
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Address
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Princess Alexandra Hospital Intensive Care 199 Ipswich Road. Woolloongabba QLD 4102
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Country
33194
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Australia
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Phone
33194
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+61 7 3176 2111
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Fax
33194
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Email
33194
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[email protected]
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Contact person for public queries
Name
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Prof Professor Balasubramanian Venkatesh
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Address
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Princess Alexandra Hospital
Intensive Care
199 Ipswich Road.
Woolloongabba QLD 4102
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Country
16441
0
Australia
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Phone
16441
0
+61 7 3176 2111
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Fax
16441
0
+61 7 3176 2155
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Email
16441
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[email protected]
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Contact person for scientific queries
Name
7369
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Prof Professor Balasubramanian Venkatesh
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Address
7369
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Princess Alexandra Hospital
Intensive Care
199 Ipswich Road.
Woolloongabba QLD 4102
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Country
7369
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Australia
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Phone
7369
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+61 7 3176 2111
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Fax
7369
0
+61 7 3176 2155
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Email
7369
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
Type
Is Peer Reviewed?
DOI
Citations or Other Details
Attachment
Study results article
Yes
Venkatesh B, etal, Adjunctive Glucocorticoid Thera...
[
More Details
]
347516-(Uploaded-26-06-2019-09-16-22)-Journal results publication.pdf
Documents added automatically
Source
Title
Year of Publication
DOI
Dimensions AI
Statistical analysis plan for the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial
2017
https://doi.org/10.1016/s1441-2772(23)00791-3
N.B. These documents automatically identified may not have been verified by the study sponsor.
Download to PDF