Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial (ARISE)

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.

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

Conditions

• Severe sepsis

Study Type

Interventional

Study Design

Treatment, Randomised, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Further Details

Primary outcome measures

• Death from all causes
  [ Time Frame: 90 days ]
  [ Designated as safety issue: No ]

Secondary outcome measures

• Death from all causes
  [ Time Frame: 28 days, and at ICU and hospital discharge ]
  [ Designated as safety issue: No ]
• Quality of life as measured by the SF-36v2, EQ-5D and the AQoL
  [ Time Frame: 6 and 12 months post-randomisation ]
  [ Designated as safety issue: No ]
• Duration of ED, ICU and hospital stay
  [ Time Frame: 28 days and 90 days ]
  [ Designated as safety issue: No ]
• The need for, and duration of, artificial organ support
  [ Time Frame: 28 days and 90 days ]
  [ Designated as safety issue: No ]

Study arms and assigned interventions

1. Standard Care: No Intervention
   • Randomised allocation of standard care at the clinician’s discretion in accordance with current best practice.
   • Other: Standard Care: Standard care at the clinician’s discretion in accordance with current best practice. Standard treatment may involve treatment with intravenous fluids, and medications to support the blood pressure and heart. Treatment is not given according to a protocol and may include some of the treatments given in the EGDT arm.
2. Early Goal Directed Therapy: Experimental
   • 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.

Study Start

October 2008 – December 2011

Eligibility & Criteria

• Ages eligible for study: 18 years and older
• Genders eligible for study: Both
• Accepts healthy volunteers: No

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 1000 mL intravenous (IV) fluid challenge within 60 minutes (including IV fluids administered pre-hospital)
  • Hypoperfusion is confirmed by the presence of a blood lactate concentration 4.0 mmol/L (Rebecca this needs to all go on the one line;
• First dose of IV antimicrobial therapy commenced prior to randomisation.

Exclusion criteria

• Age < 18 years;
• Contraindication to superior vena cava (SVC) CVC insertion;
• Contraindication 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.

Total Enrolment

1600

Contact Details

Alina Jovanovska
+61 3 9903 0280
Alina.Jovanovska@med.monash.edu.au 

Lisa Higgins
+61 3 9903 0280
Lisa.Higgins@med.monash.edu.au