Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial (ARISE)

Belinda Howe

Status and phase

Unknown

Phase 3

Conditions

Severe Sepsis

Treatments

Other: Early Goal Directed Therapy (EGDT)

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT00975793

NHMRC Project grant no. 491075

ANZIC - RC/RB001

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,600 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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