Clinical trial NCT00975793: Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial
Official title: A Multi-centre, Randomised Controlled Trial of Early Goal-directed Therapy in Patients Presenting to the Emergency Department With Severe Sepsis in Australasia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Severe Sepsis
Keywords: Sepsis
Severe sepsis
Septic shock
Lead sponsor: Monash University
Sponsor class: OTHER
Collaborators: name: Australian and New Zealand Intensive Care Society Clinical Trials Group
name: Australasian College for Emergency Medicine
First posted: 2009-09-11
Enrollment: 1600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ARISE RCT is a multi-centre, randomised, controlled trial of EGDT compared to standard care in patients with severe sepsis presenting to the ED. The study will be conducted in multiple sites with 1600 patients enrolled into the study.

Hypothesis to be tested: EGDT, compared to standard Australasian resuscitation practice, reduces 90-day all-cause mortality in patients presenting to the ED with severe sepsis.

Detailed description: The primary aim of the study is to determine whether providing EGDT, compared to standard care, reduces 90-day mortality in patients presenting to the ED of hospitals in Australasia with severe sepsis.

Each patient meeting all of the exclusion criteria and none of the exclusion criteria will be randomised in the ED to receive either EGDT for a total of 6 hours post-randomisation, or standard care.

Patients assigned to receive EGDT will be cared for by the dedicated ARISE study team. The patient will receive treatment as per the study protocol for 6 hours with central blood oxygen levels as the target end-point, then receive standard care.

Patients assigned to receive standard care will continue to be cared for by the hospital team in accordance with current best practice.

Patients in both groups will also receive any additional treatment needed, such as antibiotics or surgery.

This study will involve 1600 patients with severe sepsis admitted to the ED from multiple hospitals.

Eligibility criteria: Inclusion Criteria:

* Suspected or confirmed infection
* The presence of TWO or MORE of the following SIRS criteria:

  * Core temperature \< 36.0 degC or \> 38.0 degC
  * Heart rate \> 90 beats/minute
  * Respiratory rate \> 20 breaths/minute or PaCO2 \< 32 mmHg or the requirement for mechanical ventilation for an acute process
  * White blood cell count \> 12.0 or \< 4.0 x109/L or \> 10% immature band forms
* Evidence of either refractory hypotension OR hypoperfusion:

  * Refractory hypotension is confirmed by the presence of a systolic blood pressure (SBP) \< 90 mmHg or mean arterial pressure (MAP) \< 65 mmHg after a 1000ml intravenous (IV) fluid challenge within 60 minutes (including IV fluids administered pre-hospital)
  * Hypoperfusion is confirmed by the presence of a blood lactate concentration greater than or equal to 4.0 mmol/L
* First dose of IV antimicrobial therapy commenced prior to randomisation

Exclusion Criteria:

* Age \< 18 years
* Contra-indication to superior vena cava (SVC) CVC insertion
* Contra-indication to blood products (e.g. Jehovah's Witness)
* Inability to commence delivery of the EGDT protocol within 1 hour of randomisation or complete 6 hours of EGDT
* Haemodynamic instability due to active bleeding
* Pregnancy (confirmed or suspected)
* In-patient transfer from another acute health care facility
* An underlying disease process with a life expectancy of \< 90 days
* Death is deemed imminent and inevitable
* A "limitation of therapy" order has been documented restricting implementation of the study protocol or the treating clinician deems aggressive care unsuitable

Primary outcomes:
measure: The primary outcome measure for the study is death from all causes
timeFrame: 90 days
Secondary outcomes:
measure: Death from all causes
timeFrame: 28 days, and at ICU and hospital discharge
measure: Quality of life as measured by the SF-36v2, EQ-5D and the AQoL
timeFrame: 6 and 12 months post-randomisation
measure: Duration of ED, ICU and hospital stay
timeFrame: 28 days and 90 days
measure: The need for, and duration of, artificial organ support
timeFrame: 28 days and 90 days
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital (Sydney)
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Hornsby
country: Australia
facility: Hornsby Hospital
state: New South Wales
city: Manly
country: Australia
facility: Manly Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital (Sydney)
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Adventist hospital
state: New South Wales
city: Tamworth
country: Australia
facility: Tamworth Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Herston Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Ipswich
country: Australia
facility: Ipswich Hospital
state: Queensland
city: Meadowbrook
country: Australia
facility: Logan Hospital
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra
state: Queensland
city: Adelaide
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Modnury
country: Australia
facility: Modbury Hospital
state: South Australia
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Dandenong
country: Australia
facility: Dandenong Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital (Melbourne)
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Geelong
country: Australia
facility: Geelong Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Prahan
country: Australia
facility: The Alfred
state: Victoria
city: Sale
country: Australia
facility: Central Gippsland (Sale Hospital)
state: Victoria
city: Joondalup
country: Australia
facility: Joondalup Health Campus
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: Hong Hong
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital (HK)
city: Kowloon,
country: Hong Kong
facility: The Queen Elizabeth Hospital (HK)
city: Dublin
country: Ireland
facility: St. Vincent's University hospital
city: Otahuhu AUCKLAND
country: New Zealand
facility: Middlemore Hospital
state: Auckland
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
Study officials:
affiliation: Austin Hospital, Melbourne Australia
name: Rinaldo Bellomo
role: PRINCIPAL_INVESTIGATOR
affiliation: The Queen Elizabeth Hospital
name: Sandra L Peake
role: STUDY_CHAIR
References:
citation: Higgins AM, Peake SL, Bellomo R, Cooper DJ, Delaney A, Harris AH, Howe BD, Nichol AD, Webb SA, Williams PJ; Australasian Resuscitation in Sepsis Evaluation (ARISE) Investigators and the ANZICS Clinical Trials Group. Quality of Life and 1-Year Survival in Patients With Early Septic Shock: Long-Term Follow-Up of the Australasian Resuscitation in Sepsis Evaluation Trial. Crit Care Med. 2019 Jun;47(6):765-773. doi: 10.1097/CCM.0000000000003762.
citation: ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1.
citation: Delaney A, Peake SL, Bellomo R, Cameron P, Holdgate A, Howe B, Higgins A, Presneill J, Webb S; ARISE Investigators. Australasian Resuscitation In Sepsis Evaluation trial statistical analysis plan. Emerg Med Australas. 2013 Oct;25(5):406-15. doi: 10.1111/1742-6723.12116. Epub 2013 Sep 9.