Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multi-centre, Randomised Controlled Trial of Early Goal-directed Therapy in Patients Presenting to the Emergency Department With Severe Sepsis in Australasia

Conditions
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Severe Sepsis

Intervention / Treatment
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* Other: Early Goal Directed Therapy (EGDT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care<br>Randomised allocation of standard care at the clinician's discretion in accordance with current best practice. | |
| Experimental: Early Goal Directed Therapy<br>Randomised allocation of early goal-directed therapy (EGDT). | Other: Early Goal Directed Therapy (EGDT)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure for the study is death from all causes |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from all causes |  | 28 days, and at ICU and hospital discharge | 
| Quality of life as measured by the SF-36v2, EQ-5D and the AQoL |  | 6 and 12 months post-randomisation | 
| Duration of ED, ICU and hospital stay |  | 28 days and 90 days | 
| The need for, and duration of, artificial organ support |  | 28 days and 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Severe sepsis, Septic shock