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Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial

Phase 3
Conditions
Severe Sepsis
Registration Number
NCT00975793
Lead Sponsor
Belinda Howe
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
1600
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
The primary outcome measure for the study is death from all causes90 days
Secondary Outcome Measures
NameTimeMethod
Death from all causes28 days, and at ICU and hospital discharge
Quality of life as measured by the SF-36v2, EQ-5D and the AQoL6 and 12 months post-randomisation
Duration of ED, ICU and hospital stay28 days and 90 days
The need for, and duration of, artificial organ support28 days and 90 days

Trial Locations

Locations (51)

Canberra Hospital

🇦🇺

Garran, Australian Capital Territory, Australia

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

Coffs Harbour Hospital

🇦🇺

Coffs Harbour, New South Wales, Australia

St Vincent's Hospital (Sydney)

🇦🇺

Darlinghurst, New South Wales, Australia

Gosford Hospital

🇦🇺

Gosford, New South Wales, Australia

Hornsby Hospital

🇦🇺

Hornsby, New South Wales, Australia

Manly Hospital

🇦🇺

Manly, New South Wales, Australia

John Hunter Hospital

🇦🇺

Newcastle, New South Wales, Australia

Nepean Hospital

🇦🇺

Penrith, New South Wales, Australia

Port Macquarie Base

🇦🇺

Port Macquarie, New South Wales, Australia

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Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia

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