Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial

Severe Sepsis Clinical Trial

— ARISE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00975793
• Other study ID #: ANZIC - RC/RB001
• Secondary ID: NHMRC Project gr
• Status: Active, not recruiting
• Phase: Phase 3
• First received: September 10, 2009
• Last updated: April 23, 2014
• Start date: October 2008
• Est. completion date: April 2015

Study information

• Verified date: April 2014
• Source: Monash University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research CouncilAustralia: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1600
• Est. completion date: April 2015
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Severe Sepsis
• Toxemia

Intervention

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.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Belinda Howe	Australasian College for Emergency Medicine, Australian and New Zealand Intensive Care Society Clinical Trials Group

Countries where clinical trial is conducted

Australia,  Finland,  Hong Kong,  Ireland,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measure for the study is death from all causes		90 days	No
Secondary	Death from all causes		28 days, and at ICU and hospital discharge	No
Secondary	Quality of life as measured by the SF-36v2, EQ-5D and the AQoL		6 and 12 months post-randomisation	No
Secondary	Duration of ED, ICU and hospital stay		28 days and 90 days	No
Secondary	The need for, and duration of, artificial organ support		28 days and 90 days	No

External Links

•   ARISE study website