Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial (ARISE)

A Multi-centre, Randomised Controlled Trial of Early Goal-directed Therapy in Patients Presenting to the Emergency Department With Severe Sepsis in Australasia

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.

Study Overview

• Status: Unknown
• Conditions: Severe Sepsis
• Intervention / Treatment: Other: Early Goal Directed Therapy (EGDT)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1600
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia
      • Canberra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia
      • Royal Prince Alfred Hospital
    • Coffs Harbour, New South Wales, Australia
      • Coffs Harbour Hospital
    • Darlinghurst, New South Wales, Australia
      • St Vincent's Hospital (Sydney)
    • Gosford, New South Wales, Australia
      • Gosford Hospital
    • Hornsby, New South Wales, Australia
      • Hornsby Hospital
    • Manly, New South Wales, Australia
      • Manly Hospital
    • Newcastle, New South Wales, Australia
      • John Hunter Hospital
    • Penrith, New South Wales, Australia
      • Nepean Hospital
    • Port Macquarie, New South Wales, Australia
      • Port Macquarie Base
    • Randwick, New South Wales, Australia
      • Prince of Wales Hospital (Sydney)
    • Sydney, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia
      • Sydney Adventist Hospital
    • Tamworth, New South Wales, Australia
      • Tamworth Hospital
    • Westmead, New South Wales, Australia
      • Westmead Hospital
  • Queensland
    • Douglas, Queensland, Australia
      • Townsville Hospital
    • Herston Brisbane, Queensland, Australia
      • Royal Brisbane and Women's Hospital
    • Ipswich, Queensland, Australia
      • Ipswich Hospital
    • Meadowbrook, Queensland, Australia
      • Logan Hospital
    • Toowoomba, Queensland, Australia
      • Toowoomba Hospital
    • Woolloongabba, Queensland, Australia
      • Princess Alexandra
  • South Australia
    • Adelaide, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
    • Elizabeth Vale, South Australia, Australia
      • Lyell McEwin Hospital
    • Modnury, South Australia, Australia
      • Modbury Hospital
  • Victoria
    • Bendigo, Victoria, Australia
      • Bendigo Hospital
    • Blacktown, Victoria, Australia
      • Blacktown Hospital
    • Box Hill, Victoria, Australia
      • Box Hill Hospital
    • Clayton, Victoria, Australia
      • Monash Medical Centre
    • Dandenong, Victoria, Australia
      • Dandenong Hospital
    • Fitzroy, Victoria, Australia
      • St Vincent's Hospital (Melbourne)
    • Footscray, Victoria, Australia
      • Western Hospital
    • Frankston, Victoria, Australia
      • Frankston Hospital
    • Geelong, Victoria, Australia
      • Geelong Hospital
    • Melbourne, Victoria, Australia, 3084
      • Austin Hospital
    • Parkville, Victoria, Australia
      • Royal Melbourne Hospital
    • Prahan, Victoria, Australia
      • The Alfred
    • Sale, Victoria, Australia
      • Central Gippsland (Sale Hospital)
  • Western Australia
    • Joondalup, Western Australia, Australia
      • Joondalup Health Campus
    • Nedlands, Western Australia, Australia
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6001
      • Royal Perth Hospital
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
  • Tampere, Finland
    • Tampere University Hospital
• Hong Kong
  • Chai Wan, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital (HK)
  • Kowloon,, Hong Kong
    • The Queen Elizabeth Hospital (HK)
  • Hong Hong
    • Hong Kong, Hong Hong, Hong Kong
      • Prince of Wales Hospital
• Ireland
  • Dublin, Ireland
    • St. Vincent's University Hospital
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Auckland
    • Otahuhu AUCKLAND, Auckland, New Zealand
      • Middlemore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Care; Randomised allocation of standard care at the clinician's discretion in accordance with current best practice.
Experimental: Early Goal Directed Therapy; Randomised allocation of early goal-directed therapy (EGDT).	Other: Early Goal Directed Therapy (EGDT); Randomised allocation of early goal-directed therapy (EGDT). EGDT involves treatment with intravenous fluids, and medications to support the blood pressure and heart following a protocol. A special catheter is inserted to monitor central blood oxygen levels and the standard treatments are given according to the blood oxygen level reading. EGDT is given for 6 hours, then the patient receives standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measure for the study is death from all causes	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Death from all causes	28 days, and at ICU and hospital discharge
Quality of life as measured by the SF-36v2, EQ-5D and the AQoL	6 and 12 months post-randomisation
Duration of ED, ICU and hospital stay	28 days and 90 days
The need for, and duration of, artificial organ support	28 days and 90 days

Collaborators and Investigators

• Sponsor: Belinda Howe
• Collaborators: Australian and New Zealand Intensive Care Society Clinical Trials Group; Australasian College for Emergency Medicine
• Investigators: Principal Investigator: Rinaldo Bellomo, Austin Hospital, Melbourne Australia; Study Chair: Sandra L Peake, The Queen Elizabeth Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• ARISE study website

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): July 1, 2014
• Study Completion (Anticipated): April 1, 2015

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Estimate): April 24, 2014
• Last Update Submitted That Met QC Criteria: April 23, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Septic shock; Sepsis; Severe sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: ANZIC - RC/RB001; NHMRC Project grant no. 491075