• Patients randomised:
  • 1600
  • Sites active:
  • 42

Trial Summary

Background Synopsis

The ARISE RCT is a multi-centre, randomised controlled trial of the effect of early goal-directed therapy, compared to standard care, on 90-day mortality in patients presenting to the Emergency Department with severe sepsis in Australasia.

Patients 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, and 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.

The study will be conducted in multiple sites with 1600 patients enrolled in the study over a 2.5 year period.

Inclusion Criteria

  1. Suspected or confirmed infection
  2. AND
  3. The presence of TWO or MORE of the following systemic inflammatory response syndrome (SIRS) criteria:
    1. Core temperature < 36.0°C or > 38.0°C
    2. Heart rate > 90 beats/minute
    3. Respiratory rate > 20 breaths/minute or PaCO2 < 32 mmHg or the requirement for mechanical ventilation for an acute process
    4. White blood cell count > 12.0 or < 4.0 x109/L or > 10% immature band forms
  4. AND
  5. Evidence of either refractory hypotension OR hypoperfusion:
    1. Refractory hypotension: 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
    2. OR
    3. Hypoperfusion: confirmed by the presence of a blood lactate concentration ≥ 4.0 mmol/L
  6. AND
  7. First dose of IV antimicrobial therapy commenced prior to randomisation

Exclusion Criteria

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

Timeline for Entry into ARISE RCT

Read more in the study protocol available for download.